LIPIDS

Author: Ribosa Fornoví Isabel.
Year: 2003.
University: RAMÓN LLULL [www.url.edu].
Place of defense: Escuela Técnica Superior IQS.
Place of preparation: Escuela Técnica Superior IQS.

Summary: It has studied the process of solubilization of liposomes large (200 nm) and unilaminares of egg phosphatidylcholine and phosphatidic acid (molar ratio 9:1), for different ionic surfactants, non-ionic and anfotéricos. It has used both the absorption spectrophotometry as nuclear magnetic resonance spectroscopy of P31, for the determination of physical and chemical parameters that characterize this process: the molar ratio surfactant / phospholipid liposomes in saturated surfactant, the molar ratio surfactant / phospholipid in surfactant micelles saturated and phospholipid concentration of surfactant monomers that remain in solution in the middle. It has analyzed the influence of the molecular structure of surfactant in the values of the physical and chemical parameters obtained. In addition, considering the liposomes as structures fosfolipídicas biomiméticas, have examined the relationship between these parameters and the aquatic toxicity of surfactants observed on the species Daphnia magna.

Author: PALACIOS MARTIN LOURDES.
Year: 2004.
University: PAÍS VASCO [www.ehu.es].
Place of defense: FACULTAD DE MEDICINA Y ODONTOLOGIA.
Place of preparation: FACULTAD DE MEDICINA Y ODONTOLOGIA.

Summary: This paper addresses the identification of the protein purified from rat in our lab was called erCEH (cholesterol ester hydrolase of endoplasmic reticulum) and their possible role in lipid metabolism of hepatocytes. Its amino acid sequence revealed that the protein belongs to the family of proteins that present 4 domains SNc (Staphiloccocus Nuclease) and 1 domain Tudor. There was no sufficient evidence to attribute a cholesterol ester hydrolase activity, which has been redenominada as SND p102. In hepatocytes and CHO cells HepG2 and has inmunolocalizado basically cytoplasm, preferably in microsomes. By adenoviral infection of rat hepatocytes for sobreexpresar or nullify the expression of the protein SND p102 has been involved in the mobilization of phospholipid from the cytoplasm into secretory pathways, primarily biliary secretion, but also towards the secretion of lipoproteins, without affecting the n ° particles secreted in VLDL.

Author: CANO GONZALEZ BEATRIZ.
Year: 2004.
University: AUTÓNOMA DE MADRID [www.uam.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FUNDACION JIMENEZ DIAZ.

Summary: There are many evidences that the presence of cardiovascular risk factors (lipid disorders, obesity, diabetes, etc.) in childhood contributes significantly to the emergence of cardiovascular disease (CD) in adulthood. The levels of Dehydroepiandrosterone sulfate (DHEA-S), the principal steroid adrenal C19 segregated area of the lattice adrenal cortex, are seen as a condition of CD although literature presents major discrepancies in this regard. In adults, the ratio of DHEA-S with the EC states through its influence on traditional risk factors such as lipid levels or through its relationship with other risk factors such as obesity. Data from the relationship of DHEA-S with risk factors in children are scarce. By studying cardiovascular risk factors at the age prepubertal, 6-8 years, we see the influence of dehidroepiandrosterona-sulfato (DHEA-S), which begins to occur at this age, the effect of Apo E genotype exerted on the levels of plasma lipids. Likewise, we found that the metabolic alterations associated with obesity are changing with the age of the child pointing to the state of sexual maturation as responsible for the presence of these alterations. Such evidence led us to believe that the DHEA-S may be contributing to the levels of certain risk factors at a certain age. Therefore, we set out to analyze the hormone in 854 children age prepubertal and clarify the possible relationship of the DHEA-S with risk factors for CE in this stage of childhood. The conclusions drawn are that throughout this age of 6-8 years concentrations de DHEA-S experiencing progressive and significant increases and girls up to 8 years if de DHEA-S values are higher than those children. The most directly related to the concentrations de DHEA-S are weight, height, BMI and weight at birth. At this age the DHEA-S modulates the effect of insulin on fat levels, especially the levels of HDL-C. Finally, children who are overweight and obesity presented de DHEA-S levels significantly higher than children of normal weight and lipid abnormalities associated with obesity are modulated by the DHEA-S.

Author: ARTIEDA OSEÑALDE MARTA.
Year: 2004.
University: ZARAGOZA [www.unizar.es].
Place of defense: HOSPITAL UNIVERSITARIO MIGUEL SERVET.
Place of preparation: HOSPITAL UNIVERSITARIO MIGUEL SERVET.

Summary: The macrophages have essential functions in all stages of atherosclerosis, from the development of fat groove to the process which contributes to the rupture of the plaque and any cardiovascular event. Therefore, the identification of markers of activated macrophages has enormous interest because it can be a very useful tool to predict cardiovascular risk individuals. The enzyme quitotriosidasa, as a marker of activated macrophages could be used as a marker of atherosclerosis "in vivo". This paper described the serum activity of the enzyme quitotriosidasa was significantly elevated in subjects with pathology aterosclerosa, 153 subjects with atherothrombotic stroke and 133 subjects with ischemic heart disease, with respect to 148 control subjects. Furthermore, the serum activity quitotriosidasa increased with the degree of carotid stenosis in subjects who had submitted a atherothrombotic stroke. Moreover, the concentration of C-reactive protein in serum was significantly higher in subjects with pathology aterosclerosa respect to controls. However, there was no correlation between the serum activity quitotriosidasa and the concentration of C-reactive protein in either group of the study, indicating that both markers are mamadores inflammatory independent. In addition, we performed a prospective study of an average of 4 years with a group of subjects with ischemic heart disease to study the predictive value of serum activity quitotriosidasa in predicting cardiovascular events, and compared with that of protein C reactive. The results of the analysis indicated that the serum activity quitotriosidasa baseline predicted the risk of cardiovascular events in subjects with stable coronary artery disease in the following 4 years with a predictive value similar to that of C-reactive protein, being better marker of those events that were presented to from 2 years. In addition, the combination of the two markers improved the identification of those subjects with reduced risk of cardiovascular event. Hypercholesterolemia The Family (HF) is a disease with great variability in the response to elevated concentrations of LDL, both in the lipid phenotype, and risk of ischemic heart disease presence xantomas tendinosos (XT). The accumulation in the tendons of large amounts of lipid-laden macrophages, especially LDI. Oxidized (LDLox) is the origin of the subject XT in HF. However, it is unknown why some subjects developed HF XT and others do not. The comparison of the gene expression profile of the "pool" of macrophages from subjects with HF XT (n = 8) and without XT (n = 6) through the "microarray" expression HG-U133A of Affymetrix showed a differential gene expression in 12 genes in the absence of incubation with LDLox, and 30 genes after incubation with LDLox with fruiciones in the remodeled environment, inmunomodulación, inflammation and susceptibility to apoptosis. The macrophages from subjects with HF XT showed a differential response to LDLox, accumulating more neutral lipids (analyzed by staining cells with Red Nile and flow cytometry), greater inflammatory response and less susceptibility to apoptosis. The benefit of statins is higher than expected for his role lipid lowering, as effects on the physiology of almost all cells involved in atherogenesis, including macrófago. Most were unaware of the functions of statins in the regulation of gene expression in macrófago. Comparison of gene expression profiles using the "microarray" H 8 GU 133A 794 of the "pool" of macrófaaos (10 healthy subjects unrelated) and incubated with LDLox treated with the statin atorvastatin on "pool" of macrophages incubated alone LDLox showed a differential gene expression in 54 genes, of which 46 were sobreexpresados and 8 inhibited. Atorvastatin produced in macrophages incubated with LDLox, changes in the expression of genes involved in the endogenous synthesis of cholesterol and other metabolic pathways independent, primarily related proteins regulated by intermediaries isoprenoides and other channels regulated by transcription factors SREBP. Atorvastatin, as well as induce nail decrease in endogenous synthesis of cholesterol, regulate the entry of cholesterol to macrófago, since the protein Rab5, regulated by isoprenilación (direrencialmente expressed in response atorvastatin), were attributed a regulatory role in the endocytosis lipoprotein receptors modified using "scavenger" and regulates the eflujo cholesterol, and that esteroil-CoA desaturase (differentially expressed in response to atorvastatin) has been assigned a regulatory role in this direction, regulating the unsaturated fatty acids and the plasma membrane phospholipids, and thus the fluidity of the same.

Author: ACÍN MARTÍNEZ SERGIO.
Year: 2004.
University: ZARAGOZA [www.unizar.es].
Place of defense: FACULTAD DE VETERINARIA.
Place of preparation: FACULTAD DE VETERINARIA.

Summary: 1. The contribution of a large amount of monounsaturated fat in the form of virgin olive oil in the diet not raising the injury arteriosclerótica with respect to a diet rich in carbohydrates, in mice lacking the apolipoprotein E. However, this effect was abolished by the presence of cholesterol. 2. The components minority oil play an important role in regulating the levels of plasma triglycerides and cholesterol, as well as the modification of gene expression in the liver and regulating the injury arteriosclerótica. 3. A diet enriched in pomace oil extracted by mechanical injury decreases with respect to a diet rich in olive oil refining and increases the expression of orosomucoide which is associated with a lower expression of Mac-1 on monocytes circulating. 4. Supplementing the diet with escualeno it produces an accumulation in the liver of male mice lacking apo E is correlated with a decrease in fat liver injury and blood. By contrast, in females, this supplement does not induce escualeno of accumulation in the liver associated with a slight hepatic steatosis and unchanged in the atherosclerotic lesion. These results indicate that sex is an important factor when assessing the performance of this model in different experimental conditions. 5. Supplementing the diet with hidroxitirosol increases injury in mice devoid of apo E, which is correlated with increased expression of Mac-1 on monocytes circulating, especially in males.

Author: MORENO GUTIERREZ JUAN ANTONIO.
Year: 2005.
University: CÓRDOBA [www.uco.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: Objectives: To determine whether the polymorphism -219G / T, the developer of the ApoE determines the response and postprandial levels of the protein. Studying whether polymorphisms -219G/Ty E2/E3/E4 modify lipid levels, the susceptibility to oxidation in vitro and the size of LDL, in response to the type and quantity of fat in the diet. Materials and Methods: We performed a test overload fat in 51 healthy men apoE 3 / 3, as well as a study of intervention with 3 diets in various other 84 young healthy. The first contained a high percentage of saturated fat (TSS) (38% total fat, 20% TSS), and then were given a way randomizada crusade and a diet rich in carbohydrates (HCO) (30% fat, 55% HCO ) and the other rich in monounsaturated fat (APE) (38% fat, 22% APE). Results: Men homozygous IT showed the highest response in postprandial triglycerides, cholesterol and Retinyl palmitate in quilomicrones, as well as in ApoB-48 in the remnants of quilomicrones. Moreover, had the lowest levels of ApoE plasma during this period. The carriers of allele -219T showed a greater decrease in LDL-C and ApoB, to replace the SAT diet by diet HCO. Replacing the SAT diet by the HCO or APE, prompted a further increase in the latent phase of resistance to the oxidation of LDL in the homozygous IT. The size of LDL was greater for those apoE 4 / 3 in apoE 3 / 3 and apoE 3 / 2, regardless of the diet. Moreover, the replacement of a diet with a diet HCO APE increased the size of LDL in people apoE 3 / 3 while it declined in the apoE 4 / 3. Conclusions: IT homozygous presented lower levels of ApoE and a delay in the clearance of lipoporoteínas rich in triglycerides in the postprandial phase. The presence of allele -219T increases susceptibility to oxidation in vitro of LDL and increases plasma levels of LDL-C and ApoB to consume diet SAT, in men apoE 3 / 3. The replacement of the diet HCO by diet APE increased the size of LDL in people apoE 3 / 3, while it decreases in the apoE 4 / 3.

Author: Pérez Fernández Rebeca.
Year: 2005.
University: VALLADOLID [www.uva.es].
Place of defense: Facultad de Medicina.
Place of preparation: Facultad de Medicina.

Summary: In this paper we study the different biological functions of phospholipase A2 group VIA (iPLA2-VIA) in the cells U937. These cells are subjected to oxidative stress through treatment with hydrogen peroxide (H2O2). The conclusions that were reached was that treatment with H2O2 in cells U937 leads to the release of fatty acids including arachidonic acid (AA) through the enzyme iPLA2-VIA and without involving the cPLA2. In addition, the enzyme is involved in the hydrolysis of membrane fosfolipídica caused by H2O2, but this enzyme is not required for the process apoptótico suffering cells U937 treatment with H2O2. The lisofosfatidilcolina (lisoPC) metabolite of iPLA2-VIA helps the recognition and subsequent phagocytosis of cells U937 apoptotic. Another metabolite of iPLA2-VIA, AA, it is an important signal of cell apoptosis U937 treated with H2O2. With all these data underscore that the iPLA2-VIA not only participates in the homeostasis of the cell U937, already involved in the signaling of important events that occur inside the cell

Author: BURZACO GALÁN JAIONE.
Year: 2005.
University: PAÍS VASCO [www.ehu.es].
Place of defense: FACULTAD DE CIENCIA Y TECNOLOGÍA.
Place of preparation: FACULTAD DE CIENCIA Y TECNOLOGÍA.

Summary: The extracellular ATP inhibits platelet activation induced by ADP acting as a competitive antagonist of ADP receptor, P2Y1 and P2Y2. While other effects have been described for this nucleotide in human platelets, it has been characterized the role undertaken by the nucleotide of pruina in platelet activation induced by tormbina. In order to investigate the interaction with the extracellular ATP surface plaquetria, have been characterized mechanisms of inhibition exerted on the thrombin signaling in this cell type. The results show that the ATP increased cAMP levels in a concentration-dependent and time of incubation. We note also that in the presence of acid nordihidroguaiarético (NDGA) or 15 (S) -hidroxieicosatetraenoico inhibiting the 12-lopoxigenasa, reverses significantly inhibiting nucleotide. Moreover, while the ATP blocking increased levels of acid, 12 (S) -hidroxieicosatetraenoico, does not diminish the formation of its precursor, acid 12 (S) -hidroperoxieicosatetraenoico stimulated by thrombin. The preincubation with SQ-22536 (inhibitor of adenilato cyclase) and NDGA reverts almost completely inhibition in the presence of specific nucleotide. Therefore, we concluded that the extracellular ATP exerts its inhibitory effect on platelet activation induced by thrombin through at least two different signaling pathways and independent: 1-Antagonizando with the receiver P2Y12, thus blocking the inhibition of adenilato cyclase. 2-Through another receiver Q2 yet characterized, coupled with the route of 12-lipoxigenasa. Studies with aspirin and indomethacin indicate that the receiver P2Y2 is not responsible for the effect of ATP. In addition, experiments PPADs indicate that neither the receiver P2X1 nor P2Y1 involved in the inhibition. The use of AR-C67085, receptor antagonist P2Y12 and agonist-receptor P2Y11 shows that the receiver P2Y11 Nor is involved. With a new receiver purinérgico P2X may be involved in the inhibition conducted by the ATP, allowing block thrombin.

Author: RUIZ LÓPEZ NOEMÍ.
Year: 2005.
University: SEVILLA [www.us.es].
Place of defense: INSTITUTO DE LA GRASA (CSIC) SEVILLA.
Place of preparation: INSTITUTO DE LA GRASA (CSIC). SEVILLA.

Summary: The objectives of this were Doctoral Thesis: FIRST develop an analytical method for rapid extraction of oil from half seed, in order to determine accurately the molecular species composition of triacilglicéridos in oil sunflower half by gas chromatography liquid. SECOND Define a mathematical ratio that indicates the distribution of saturated fatty acids between the positions sn-1 and sn-3 of triacilglicérido. THIRD Biochemical Characterization of activities aciltransferasas (GPAT and LPAAT) microsomal sunflower responsible for the synthesis of TAGs and therefore, the final proportion of the various species of TAGs in a sunflower oil. FOURTH partial purification of GPAT in order to get their sequence anminoacídica. FIFTH Cloning and sequencing of the donor electron desaturasas plastidiales, ferredoxina sunflower. The findings were: 1, has been developed a rapid method for extracting triacilglicéridos (TAGs), based on the extraction of vegetable oils tissue, using a mixture composed of a 33.3% methanol with NaCl (0.17 M) and 66.6% by volume of heptane. 2 - The optimum extraction of TAGs, in a sample plant, was achieved after an incubation of this sample in the mixture for 2 hours at 80Â ° C. The composition of TAGs gathered is representative of all those found in plant tissues. The TAGs stadiums can be subsequently metilados to get the fatty acid composition, allowing analysis of their methyl esters in the same tissue sample. 3-This method allows the TAGs extraction of a large number of small plant samples. And it is therefore very useful for the selection of new varieties of plants, taking into account the composition in the TAGs and fatty acids of seeds and fruits because it remains intact embryo. 4 - The mathematical coefficient to SAT, which has been developed in this paper allows the calculation of the relative distribution of the saturated fatty acids between the external positions sn-1 and sn-3 in the TAGs. This coefficient can be calculated if one knows the total membership of saturated fatty acids of the TAGs, the composition of fatty acids in the position sn-2, and molecular species of TAGs. 5 - The study of the coefficients aSat indicated the existence of a high degree of asymmetry in the distribution of saturated fatty acids, between the positions sn-1 and sn-3 of the species of TAGs all oils studied, except if oil rice. 6, - also from aSat, you can calculate the distribution of fatty acid in particular in the molecular TAGs a certain oil. 7-Techniques rapid analysis of the composition of TAGs and fatty acids, which have been developed in this paper, data from loa composition of fatty acids in the position sn-2, and the corresponding coefficient of asymmetry aSat calculated on the basis of this information, allow selection of acitransferasas that alleles differ in their specific for the different fatty acids. 8 - The study of the kinetic parameters, the acil-transferasas glycerol apparent phosphate aciltransferasa (GPAT) and lisofosfatidato aciltransferasa (LPAAT) by their respective substrates, glycerol 3-fosfato and lisofosfatidato respectively, showed similar values for the affinity constant, 353 and 226 uM, and a maximum speed 25 times lower for the GPAT, pointing to this activity as the determinant of the rate of synthesis of TAGs for the development of sunflower seed. 9 - The activity GPAT 8 is not vi a22 or stimulated with the use of cations Mg2 + and Mn2 +, but when it was tested with EDTA, 10 mM. The pH optimum acilación for GPAT and LPAAT in microsomes developing sunflower seeds was 7.5 and 8.5, respectively. The maximum activity GPAT and LPAAT on seeds were found in younger (11 and 15 FDA), seeds that are at the beginning of the active phase of lipid synthesis. 10 - The GPAT showed a broad specificity for all acil-CoAs tested, except for estearil-CoA. And, as has already been seen in other species of oilseed plants, the best substrate for this enzyme was palmitil-CoA. 11 - The LPAAT presented a great specificity by oleil-CoA and very low specificity linoleil-CoA, which contrasts with the high content of this fatty acid in the position sn-2 of TAGs. This suggests that much of oleic acid incorporated into the position sn-2f is exchanged by the linoleic acid present in the molecules of phosphatidylcholine, which the concentration of oleic and linoleic acid at position sn-2 does not reflect the activity LPAAT but the other enzymes involved in the transfer of fatty acids with phosphatidylcholine. 12, has been achieved partial purification of GPAT microsomal sunflower after solubilization with Tween80 and after two chromatographic steps: anion exchange chromatography followed by gel filtration chromatography. An analysis by SDS-PAGE of the fraction purification, have yielded several bands of different sizes, as potential candidates for this enzyme. 13 - The gene Hafdx2 identified from sunflower seeds encodes for a ferredoxina heterotrophic. While his sequence and structural model are similar to those of other ferredoxinas described in plants, defers the ferredoxina photosynthetic sunflower previously cloned in our laboratory.

Author: GONZÁLEZ LÓPEZ MARIA MÓNICA.
Year: 2005.
University: PAÍS VASCO [www.ehu.es].
Place of defense: FACULTAD DE CIENCIA Y TECNOLOGÍA.
Place of preparation: FACULTAD DE CIENCIA Y TECNOLOGÍA.

Summary: In recent years have made great strides in terms of the biology of lipids. Today we know that the bioactive lipid regulating many cellular functions. The working hypothesis of this dissertation is that the acid lisofosfatídico (LPA), the sphingosine 1 phosphate (S1P) and cerámido 1 phosphate (C1P), important bioactive lipid, regulate the inflammatory processes in macrophages and fibroblasts. The objectives to demonstrate this scenario are as follows: 1-Studying whether the LPA, S1P and C1P are able to modulate the migratory process in different cell types. For this to be carried out experiments with the migration of fibroblasts and macrophages. 2-Investigating transduction pathways involved in the migration processes covered by these bioactive lipids. 3-To determine the potential effects of C1P in the inflammatory processes in macrophages. 4-Consider the mechanisms through which the C1P regulates these inflammatory processes.

Author: MARTÍNEZ SALAZAR ROSA M..
Year: 2005.
University: PAÍS VASCO [www.ehu.es].
Place of defense: FACULTAD DE MEDICINA Y ODONTOLOGÍA.
Place of preparation: FACULTAD DE MEDICINA Y ODONTOLOGÍA, UPV/EHU.

Summary: Free radicals can react with cellular constituents modifying cell parameters and / or act as second messengers. Studies previously showed that tert-butilhidroperóxido (TBHP), an oxidizer used as a model to study the mechanism of alterations caused by the action of free radicals cause oxidative stress in hepatocytes and release of arachidonic acid (AA) in the middle, as well as increases intracellular of diacilglicerol (DAM) and AA. This work continues the same line investigaicón expand the study to other oxidants more physiological meaning that the TBHP. It proposes two models of species radicalarias or generating free radicals: A-Doxorubicin, a anticarcinogenic able to cross the plasma membrane of the liver and cause reactive species during their metabolism, which have been associated with toxicity produced. B-ferrilmioglobina (ferrilMb), a protein hémica nature radicalaria, formed by reacting the metamioglobina with H2O2 and that has been detected in vivo. The goal that arises is studying the influence of oxidizing previous parameters indicative of oxidative stress, the production of lipid mediators and the main pathways of these actions within the cell, and as affecting the metabolism and lipid secretion in isolated hepatocytes rat. The results obtained highlight it below. Doxorubicin produced no hepatocyte cytotoxicity only decreasing the levels of GSH. Doxorubicin increased intracellular levels of DAG and ceramide, and induced changes in the state of cellular protein phosphorylation. The accumulation of DAG in the cell is partly due to the activation of phospholipase C-specific PIP2, and on the other hand, the decline dela synthesis hepatic glicerofosfolípidos and triacilglicéridos, so that the DAG accumulates inside the cell. The availability of lipids is smaller, so it decreases the secretion of VLDL in the presence of doxorubicin. The ferrilMB, although induced oxidative stress, did not affect the production of any of the lipid mediators studied. The ferilMb blocked the secretion of VLDL like doxorubicin, but in a way dependent on lipoperoxidación and using different mechanism.

Author: SALVADOR IBAÑEZ ANA M..
Year: 2005.
University: PAÍS VASCO [www.ehu.es].
Place of defense: FACULTAD DE CIENCIA Y TECNOLOGÍA.
Place of preparation: FACULTAD DE CIENCIA Y TECNOLOGÍA.

Summary: Carotenoids are a group of fat-soluble pigments widely distributed in nature and while pigments are very common in plants, only a limited number of them are found in human plasma and tissues and their transport is mediated by lipoproteins. Lipoproteins are structurally macromolecules that are formed on the one hand by a lipid and protein, whose function is to pack lipid insoluble from the diet and synthesized by the body itself and transported from the gut and liver to peripheral tissues and for them to the liver, returning there cholesterol to the liver for disposal in the form of bile acids. Carotenoids are also united to form complex proteins called carotenoproteínas that are characteristic of, among others, crustaceans. The present work has been studied in Chapter 1 the effect of fish oil on the storage of astaxantina into the muscle of trout and the effects on the blood serum lipoproteins. Chapter 2, is about the effect of vehiculización of carotenoids with phospholipids and their accumulation in the muscle of rainbow trout. In chapter 3, explores the union of cetocarotenoide astaxantina with high-density lipoprotein (HDL) trout and it is found that there is no changes in the structure of these lipoproteins. In chapter 4, astaxantina will merge, in this case, lipoproteins the egg yolk purified by ultracentrifugation. Finally, in Chapter 5 is a purified lipoprotein vegetable oils and compared this protein with the normal areas of the area affected by the alteration 'green spot'.

Author: BRIZUELA MADRID LEYRE.
Year: 2005.
University: PAÍS VASCO [www.ehu.es].
Place of defense: FACULTAD DE CIENCIA Y TECNOLOGÍA.
Place of preparation: FACULTAD DE CIENCA Y TECNOLOGÍA.

Summary: The biosynthesis of aldosterone is regulated primarily by the hormone ACTH, angiotensin-II (Ang-II) and K +, however, there are many other molecules capable of controlling the secretion of this mineralocorticoid. The esfingolípidos are bioactive lipid regulating large number of functions such as cell proliferation, survival, differentiation and cell cycle. In addition, they can act as powerful second messengers and stimulate different processes within the cell such as migration or inflammatory response. However, no data exist in the literature of his involvement in steroid secretion. One of the most important findings in this dissertation is the discovery of two new regulators aldosterone secretion, esfingosina-1-fosfato (Sph-1-P) and cerámido natural phosphate (Cer 1-P). The Sph-1-P stimulates aldosterone secretion through a mechanism in which participates PKC-alfa, PKC- *, and the Ca2 + extracellular proteins Gi, in which the metabolic pathways are activated PLD / PAP MEK / ERK1-2 and Pl3-K/PKB. Moreover, Cer 1-P stimulates aldosterone secretion through a mechanism that also involved Gi protein and the activation of signaling pathways MEK / ERK 1 / 2 and Pl3-K/PKB but not PLD / PAP.

Author: MATABOSCH GERONÉS XAVIER.
Year: 2006.
University: BARCELONA [www.ub.es].
Place of defense: FACULTAD DE QUÍMICA.
Place of preparation: INSTITUT D'INVESTIGACIONS QUÍMIQUES I AMBIENTALS DE BARCELONA (CSIC).

Summary: In recent years it has been shown that lipids are not only structural components of the plasma membrane else who develop different cellular functions. Specifically it has been observed that the degradation products of fosfolipasas are important in the processes of inflammation, among others, and it seems that the phospholipase A2 independent of calcium could be related to schizophrenia. The synthesis of new potential inhibitors of this protein to study the metabolism of these lipids has been ele main objective during this dissertation. That of course will have analogues synthesized from the only selective inhibitor of this enzyme (BEL) but with different amendments to try to obtain a reversible inhibitor equally selective. One of these changes was the introduction of the functionality trifluorocetona common in different inhibitors lipases, in the shell of BEL, but none with high-capacity product inhibition. It also introduced groups ariloxi- in the structure, in this case nor did well inhibitors, but interestingly two of these compounds argued twice the activity of the enzyme selectively respect to another PLA2. Another approach to developing new synthesis inhibitors was similar substrate with a group of n-hexadecilmercaptato in position sn-1 and the group fosforilcolina in position sn-3 skeleton of glycerol, with different functionalities (Amida, carbamate, sulphonamide ..) and side chains in the position sn-2. In this case, some of the compounds synthesized presented remarkable levels of inhibition, however, when he studied selectivity versus cPLA2 was also noted that inhibited the activity of this enzyme. In addition to better understanding the structure of the active center and designing better inhibitors were cloned and expressed two fragments from the center of the active enzyme. Unfortunately these fragments were expressed in small quantities and were added in inclusion body, it did not allow its purification. During the argument, was also prepared various analogues ceramide. Trials of activity of these compounds in different enzyme metabolism esfingolípidos showed that it had synthesized a new family of compounds that opens a new line of development in the field of esfingolípidos. And it has obtained the best so far described inhibitor of the enzyme esfingomielina synthase.

Author: JIMENEZ GOMEZ YOLANDA.
Year: 2006.
University: CÓRDOBA [www.uco.es].
Place of defense: FACULTAD DE CIENCIAS.
Place of preparation: FACULTAD DE CIENCIAS.

Summary: MAIN GOAL determine the long-term effect of a Mediterranean Diet, regarding a Western Diet and other diet rich in carbon hydrates (HC) and polyunsaturated fatty acids (AGPs) n-3 plant, on the activation of NF-kB in peripheral blood mononuclear cells (PBMCs) of healthy individuals by the end of the period of dietary intervention and during the postprandial state. SECONDARY OBJECTIVES establish the effect of three models of food in the gene expression of MCP-1, IL-6 and TNF in the PBMCs, at the end of the dietary intervention and during postprandio. In these periods of study to determine the response of the molecules ICAM-1, VCAM-1, MCP-1, IL-6 and TNF-aa plasma level, and analyze the association of inflammation with the lipid profile and oxidative stress. DESIGN AND METHODOLOGY were selected twenty healthy subjects, normolipémicos and homozygous for the allele E3 of the apoE. All volunteers followed by three periods of dietary intervention of four weeks each, according to a randomized and crossover design: Diet rich in saturated fatty acids (AGSs), monounsaturated fatty acids (AGMs), and HC and AGPs n -3 vegetable. After 12h fasting, all participants were given a breakfast rich in fat composition equal to that consumed each in periods of dietary intervention: Breakfast rich in butter, rich in olive oil and rich in nuts. RESULTS Under conditions of fasting, the Mediterranean diet, at 4 weeks, produces a lower activation of NF-kB in PBMCs, compared to the West. Moreover, the Western diet induces an increase in the levels of TNF-mRNA of the gene, compared with the Mediterranean and MCP-1, concerning the diet HC and AGPs n-3 in PBMCs. Also, there was a larger increase in sVCAM-1 with the intake of the diet AGSs than with the other two diets. In the postprandial state, we note that a breakfast rich in butter produces increased levels of mRNA of TNF-ae PBMCs, compared with the two other fat overload, and that the breakfast rich in butter and olive oil, producing greater postprandial response the mRNA of IL-6 that the rich in nuts. Finally, we demonstrate that with breakfast rich in butter or nuts is greatest plasma levels of VCAM-1 compared to the rich in olive oil, at 3h of fat intake. MAIN CONCLUSIONS: The daily consumption of a Mediterranean diet reduces the activation of NF-kB in PBMCs from healthy individuals, compared with the West. The diet HC and AGPs n-3 vegetable shows no difference in the activation of this factor with respect to the Western diet. In the state postparandial there was no difference in this parameter between the three models diets studied. SECONDARY 1, - PBMCs obtained after the Western diet showed an increase in the gene expression of TNF-ay MCP-1 with respect to the Mediterranean and the rich in HC and AGPs n-3 vegetable, respectively. In the postprandial state, triggering an increase in the mRNA of TNF with breakfast rich in butter over the other two breakfasts, and greater postprandial response of the mRNA of IL-6 with the overload rich in butter and olive oil compared to the rich in nuts. 2 - The Western diet produces an increase in the concentration sVCAM-1 compared with the other two diets. In the postprandial period, it results in an increase in plasma levels after breakfast rich in butter and nuts, compared with the olive oil, at 3h of the overhead. 3 - The observed variations in sVCAM-1 was positively associated with the levels of c-HDL in the fasting state, and negatively with those of LPOs and triglycerides in the postprandial period.

Author: CATURLA CERNUDA NURIA.
Year: 2006.
University: MIGUEL HERNÁNDEZ DE ELCHE [www.umh.es].
Place of defense: INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR.
Place of preparation: INSTITUTO DE BIOLOGÍA MOLECULAR Y CELULAR DE LA UMH.

Summary: We analyzed the biological activities of plant compounds with different backgrounds: You and Olive. With each of them have different objectives and different methodologies are used. With regard to the catechins flavonoids in green tea are evaluated firstly its antioxidant activity, both in synthetic vesicles system as in mitochondrial preparations. It determines which are the gallates of catechin the most effective inhbidores of lipid peroxidation. We have studied in detail the interaction of gallates of catechin Membrane: these molecules are incorporated into the membrane, increasing the management of lipids, leading to increased resistance of the membrane to the solubilization by non-ionic detergent. He then discusses the antibacterial activity of lso gallates of catechin: the authors conclude that the bactericidal activity is based on the ability of these compounds interact with the bacterial membrane and destabilize it. In the next chapter of the report discusses the properties of an olive leaf extract. In particular, the activity of complete and its majority component, oleuropeína in inhibiting replication of the virus hemorrhagic septicemia virus (VHSV), a pathogenic role in the cultivation of rainbow trout in farmed. Tests in cell culture demonstrating the antiviral activity of both compounds. It proposes a mechanism of action based on the direct inactivation of viral particle. The activity against VHSV other components minority of olive leaf extract is also analyzed.

Author: SÁNCHEZ BAUTISTA SONIA.
Year: 2006.
University: MURCIA [www.um.es].
Place of defense: FACULTAD DE BIOLOGÍA.
Place of preparation: FACULTAD DE VETERINARIA.

Summary: The Protein Quinasa C (PKC) is involved in many cellular processes and signaling is involved in many physiological functions such as growth, cell differentiation, apoptosis, immune response, hormonal secretion, among others. In this thesis has studied the role of the regulatory region of the isoenzymes classic and new. It has also been studied secondary structure of the catalytic domain of an isoenzyme atypical: PKC zeta. Within the region there are two regulatory domains, the C1 is linked to diacilglicerol (DAM) and phorbol esters and mastery C2 than in a conventional PKC anionic phospholipids in the presence of calcium and the new PKC does in a way independent calcium. For his part, the catalytic domain contains binding sites of the ATP and the substrate capable of phosphorylation by PKC.Teniendo the foregoing, the present thesis has been studied: i) the binding affinity domain C2 alpha to fosfatidilinositol-4 ,5-bisfosfato (PIP2), ii) how changes in phosphatidic acid formation and reorganization as a result of interaction with the domain C2 epsilon iii) the binding capacity of different domains C1B of classic and new isoenzymes different types of DAG and in the presence of lipids negative iv) the secondary structure of the catalytic domain of PKC zeta and how it modulates the presence of ligand Mg2 + -ATP well as their behavior with respect to thermal denaturation. The use of different techniques and different mutants has allowed us to determine that the domain C2 alpha interacts with a molecule of PIP2 in a manner dependent calcium through the region rich in lisinas. A more extensive study using different types of fosfoinosítidos has shown that the presence of negative charges is not decisive in the interaction domain C2 with fosfoinosítido but there is a specific component for the type of lipid introducing special preference for the PIP2. For its part, the domain C2 epsilon presents special preference for lipid phosphatidic acid as compared to others such as phosphatidylcholine establishing a type of electrostatic interaction with the first to be manifested by an amendment to the transition temperature, a decrease of the peak at low field isotropic phosphatidic acid as well as a widening of the same and a decrease in times of relaxation at all temperatures studied. In addition, structurally manifested in a change conformacional in the head polar phosphatidic acid. In addition to studying the different domains C1B of classical isoenzymes (alpha and gamma) and new (delta and epsilon) showed a gradual increase in the affinity under increased the concentration of lipid negative and / or DAG. The domain C1B epsilon was the greatest affinity introduced in all cases studied experimental, introducing special preference for the phospholipid mixtures containing negative phosphatidic acid and diacilglicerol DOG (1,2-sn-dioleilglicerol). Finally, the secondary structure of the catalytic domain of PKC zeta determined by infrared spectroscopy, is flexible and changes in the presence of ligand Mg2 + -ATP. It also exerts a protective effect against the thermal denaturation. The experiments show two-dimensional correlation of the sequential order in which they arise changes in the secondary structure of the effect of temperature, which appreciated differences between the terms of presence and absence of Mg2 + -ATP.