Alejandro Zentella-Dehesa

Publications of Alejandro Zentella-Dehesa

• Placental blood leukocytes are functional and phenotypically different than peripheral leukocytes during human labor.

  Authors: Rodrigo Vega-Sanchez, Nardhy Gomez-Lopez, Arturo Flores-Pliego, Susana Clemente-Galvan, Guadalupe Estrada-Gutierrez, Alejandro Zentella-Dehesa, Rolando Maida-Claros, Jorge Beltran-Montoya, Felipe Vadillo-Ortega

  Journal of reproductive immunology. 09/2009;

  Rupture of the fetal membranes during human labor is associated with an inflammatory process localized to the maternal-fetal interface. There is evidence that specific leukocytes subsets areRupture of the fetal membranes during human labor is associated with an inflammatory process localized to the maternal-fetal interface. There is evidence that specific leukocytes subsets are attracted to the choriodecidua, and that after homing they condition a local inflammatory microenvironment, possibly being directly involved in rupture of the membranes. In this study our aim was to compare the phenotypes and function of leukocytes located in the placental intervillous blood with peripheral leukocytes obtained before or after labor, including expression of modulators of inflammation in these cells. Flow cytometry revealed that the proportion of CD14(+) cells is increased in intervillous blood, suggesting the participation of monocytes/macrophages during labor. Real time qRT-PCR showed that at term gestation and particularly during labor, placental blood leukocytes adopt a different expression pattern of pro-inflammatory cytokines than leukocytes in peripheral blood, including IL-1beta and IL-1RA. During labor, both placental and peripheral leukocytes increase their secretion of matrix metalloproteinase-9. Moreover, we showed that placental leukocytes respond differently than peripheral leukocytes to bacterial lipopolysaccharide, secreting differential amounts of TNF-alpha, IL-1beta and IL-6. Finally, a preliminary proteomic characterization of placental leukocytes revealed a significantly higher number of individual proteins than in peripheral leukocytes. Our results support the existence of selective subsets of leukocytes recruited to the maternal-fetal interface that may participate in the triggering of parturition.

• Mycobacterial di-O-acyl trehalose inhibits Th-1 cytokine gene expression in murine cells by down-modulation of MAPK signaling.

  Authors: José Prisco Palma-Nicolás, Rogelio Hernández-Pando, Erika Segura, María J Ibarra-Sánchez, Iris Estrada-García, Alejandro Zentella-Dehesa, Luz M López-Marín

  Immunobiology. 06/2009;

  Protection against tuberculosis (TB) is based on cell-mediated immune responses. TB is often characterized by immunological dysfunction of peripheral blood mononuclear cells, especially at chronicProtection against tuberculosis (TB) is based on cell-mediated immune responses. TB is often characterized by immunological dysfunction of peripheral blood mononuclear cells, especially at chronic stages. Lipids from the Mycobacterium tuberculosis cell wall have been shown to produce various suppressive effects on cell-mediated immunity. The cell-surface lipid di-O-acyl-trehalose (DAT) is able to inhibit T-cell proliferation and cytokine secretion in cells from naïve mice. In the present study, we addressed the mechanisms involved in the suppressive effect caused by DAT. We found that DAT decreased the proliferation of spleen cells induced with PMA-ionomycin, suggesting that the suppressive mechanisms target intracellular functions just after phospholipase C-gamma activation. Addressing this possibility, the effect of DAT was found to involve down-modulation of the di-acyl glycerol-dependent activation of the MAPK-ERK1/2 pathway, one of the crucial signaling pathways leading to adaptive cell immune response against TB. Moreover, the inhibitory effect of DAT on proliferation was reproduced in antigen-stimulated T cells from M. tuberculosis-infected mice, involving the lowering of Th1-type cytokine transcription levels. The present findings thus reveal a new kind of bioactivity for a long-known M. tuberculosis cell wall lipid, DAT.

• Ethanol-mediated oxidative changes in blood lipids and proteins are reversed by aspirin-like drugs.

  Authors: Martha Zentella de Piña, Adrián Sandoval-Montiel, Laura Serrano-Alessandri, Eduardo Montalvo-Jave, Alejandro Zentella-Dehesa, Enrique Piña

  Archives of medical research. 05/2007; 38(3):269-75.

  BACKGROUND: Previous work from our laboratory revealed that administration of selected nonsteroidal anti-inflammatory drugs (NSAIDs)-aspirin, naproxen, nimesulide, and piroxicam-prevented some signsBACKGROUND: Previous work from our laboratory revealed that administration of selected nonsteroidal anti-inflammatory drugs (NSAIDs)-aspirin, naproxen, nimesulide, and piroxicam-prevented some signs of oxidative stress produced in rat livers acutely intoxicated with ethanol. Our final aim was to pursue these advantageous effects of NSAIDs in humans in relation to opposing the oxidative action of ethanol. In preparation for these studies, we conducted a search for tissues that were more accessible than liver, such as plasma and blood cells. METHODS: Either ethanol (5 g/kg body weight) or an isocaloric amount of glucose from a 30% solution alone or combined with one of the NSAIDs was administered orogastrically to rats; animals were sacrificed 5 h later. RESULTS: Ethanol increased both protein carbonylation (PCO) and thiobarbituric acid reactive substances (TBARS) in isolated lymphocytes, increased proteolysis in isolated red blood cells (RBC), and decreased the pool of plasma amino acids. The NSAIDs employed reversed the ethanol-mediated rise in PCO in plasma, but with the exception of aspirin failed to prevent the ethanol-produced decrease in the amino-acid serum pool. Additionally, the increase in TBARS and PCO promoted by ethanol in lymphocytes was reverted with aspirin. In contrast, ethanol-activated proteolysis was not modified by aspirin. CONCLUSIONS: The pro-oxidant effects of ethanol and certain beneficial actions of NSAIDs, especially those of aspirin, preventing these pro-oxidant effects can be followed in blood constituents of rats. Hence, these oxidative markers could be regarded as potential clinical monitors for ethanol-mediated oxidative stress.

• NF-kappaB activation but not PI3K/Akt is required for dexamethasone dependent protection against TNF-alpha cytotoxicity in L929 cells.

  Authors: Criselda Mendoza-Milla, Catalina Machuca Rodríguez, Emilio Córdova Alarcón, Adriana Estrada-Bernal, E Mayra Toledo-Cuevas, Eduardo Martínez Martínez, Alejandro Zentella-Dehesa

  FEBS letters. 08/2005; 579(18):3947-52.

  Tumor necrosis factor alpha (TNF-alpha) is one of the best-described cell death promoters. In murine L929 fibroblasts, dexamethasone inhibits TNF-alpha-induced cytotoxicity. Since phosphatidylTumor necrosis factor alpha (TNF-alpha) is one of the best-described cell death promoters. In murine L929 fibroblasts, dexamethasone inhibits TNF-alpha-induced cytotoxicity. Since phosphatidyl inositol 3 kinase (PI3K) and nuclear factor kappa B (NF-kappaB) proteins regulate several survival pathways, we evaluated their participation in dexamethasone protection against TNF-alpha cell death. We interfered with these pathways by overexpressing a negative dominant mutant of PI3K or a non-degradable mutant of inhibitor of NF-kappaB alpha (IkappaBalpha) (the cytoplasmic inhibitor of NF-kappaB) in L929 cells. The mutant IkappaB, but not the mutant PI3K, abrogated dexamethasone-mediated protection. The loss of dexamethasone protection was associated with a diminished accumulation in XIAP and c-IAP proteins.

• The inhibitor protein of the F1F0-ATP synthase is associated to the external surface of endothelial cells.

  Authors: Paulina Cortés-Hernández, Lenin Domínguez-Ramírez, Adriana Estrada-Bernal, Delina G Montes-Sánchez, Alejandro Zentella-Dehesa, Marietta Tuena de Gómez-Puyou, Armando Gómez-Puyou, José J García

  Biochemical and biophysical research communications. 06/2005; 330(3):844-9.

  The ATPase inhibitor protein (IP) of mitochondria was detected in the plasma membrane of living endothelial cells by flow cytometry, competition assays, and confocal microscopy of cells exposed to IPThe ATPase inhibitor protein (IP) of mitochondria was detected in the plasma membrane of living endothelial cells by flow cytometry, competition assays, and confocal microscopy of cells exposed to IP antibodies. The plasma membranes of endothelial cells also possess beta-subunits of the mitochondrial ATPase. Plasma membranes have the capacity to bind exogenous IP. TNF-alpha decreases the level of beta-subunits and increases the amount of IP, indicating that the ratio of IP to beta-subunit exhibits significant variations. Therefore, it is probable that the function of IP in the plasma membrane of endothelial cells is not limited to regulation of catalysis.

• A novel ARH splice site mutation in a Mexican kindred with autosomal recessive hypercholesterolemia.

  Authors: Samuel Canizales-Quinteros, Carlos A Aguilar-Salinas, Adriana Huertas-Vázquez, María L Ordóñez-Sánchez, Maribel Rodríguez-Torres, José L Venturas-Gallegos, Laura Riba, Salvador Ramírez-Jimenez, Rocío Salas-Montiel, Giovani Medina-Palacios, Ludivina Robles-Osorio, Angel Miliar-García, Luis Rosales-León, Blanca H Ruiz-Ordaz, Alejandro Zentella-Dehesa, Adrian Ferré-D'Amare, Francisco J Gómez-Pérez, Ma Teresa Tusié-Luna

  Human genetics. 01/2005; 116(1-2):114-20.

  Autosomal recessive hypercholesterolemia (ARH) is characterized by elevated LDL serum levels, xanthomatosis, and premature coronary artery disease. Three loci have been described for this conditionAutosomal recessive hypercholesterolemia (ARH) is characterized by elevated LDL serum levels, xanthomatosis, and premature coronary artery disease. Three loci have been described for this condition (1p35, 15q25-q26 and 13q). Recently, the responsible gene at the 1p35 locus, encoding an LDL receptor adaptor protein (ARH) has been identified. We studied a Mexican ARH family with two affected siblings. Sequence analysis of the ARH gene (1p35 locus) revealed that the affected siblings are homozygous for a novel mutation (IVS4+2T>G) affecting the donor splice site in intron 4, whereas both the parents and an unaffected sister are heterozygous for this mutation. The IVS4+2T>G mutation results in a major alternative transcript derived from a cryptic splice site, which carries an in-frame deletion of 78 nucleotides in the mature mRNA. The translation of this mRNA yields a mutant protein product (ARH-26) lacking 26 amino acids, resulting in the loss of beta-strands beta6 and beta7 from the PTB domain. This is the first case where a naturally occurring mutant with an altered PTB domain has been identified.

• Steroid 21-hydroxylase (P450c21) naturally occurring mutants I172N, V281L and I236n/V237E/M239K exert a dominant negative effect on enzymatic activity when co-expressed with the wild-type protein.

  Authors: Xóchitl Félix-López, Laura Riba, M Luisa Ordóñez-Sánchez, Salvador Ramírez-Jiménez, José Luis Ventura-Gallegos, Alejandro Zentella-Dehesa, M Teresa Tusié-Luna

  Journal of pediatric endocrinology & metabolism : JPEM. 10/2003; 16(7):1017-24.

  Steroid 21-hydroxylase deficiency is the major cause of congenital adrenal hyperplasia, an autosomic recessive disorder that affects the synthesis of aldosterone and cortisol. The disease presents aSteroid 21-hydroxylase deficiency is the major cause of congenital adrenal hyperplasia, an autosomic recessive disorder that affects the synthesis of aldosterone and cortisol. The disease presents a wide spectrum of clinical phenotypes as a result of the combination of different mutant alleles. Due to the adrenal-specific expression of the enzyme, the study of the functional effect of different mutations is only possible through in vitro expression studies. Determination of the functional effect of independent mutations does not always result in clear phenotype-genotype correlations, particularly in those patients with different mutations in the two alleles (compound heterozygotes). In this study we show that co-expression of the mutant proteins I172N, V281L or I236N/V237E/M239K with the wild-type enzyme resulted in an apparent dominant negative effect on the enzymatic activity of the latter, while co-expression with the mutant enzyme R356W does not show this effect.

• Locus on chromosome 6p linked to elevated HDL cholesterol serum levels and to protection against premature atherosclerosis in a kindred with familial hypercholesterolemia.

  Authors: Samuel Canizales-Quinteros, Carlos A Aguilar-Salinas, Eduardo Reyes-Rodríguez, Laura Riba, Maribel Rodríguez-Torres, Salvador Ramírez-Jiménez, Adriana Huertas-Vázquez, Verónica Fragoso-Ontiveros, Alejandro Zentella-Dehesa, José L Ventura-Gallegos, Gerardo Vega-Hernández, Angelina López-Estrada, Moisés Aurón-Gómez, Francisco Gómez-Pérez, Juan Rull, Nancy J Cox, Graeme I Bell, Maria Teresa Tusié-Luna

  Circulation research. 04/2003; 92(5):569-76.

  Heterozygous familial hypercholesterolemia (FH) is a highly atherogenic genetic disorder leading to premature coronary heart disease (CHD), usually before 60 years of age. We studied an extendedHeterozygous familial hypercholesterolemia (FH) is a highly atherogenic genetic disorder leading to premature coronary heart disease (CHD), usually before 60 years of age. We studied an extended multigenerational kindred with FH linked to chromosome 1p32 in which atherosclerotic complications were either delayed or prevented in individuals with elevated HDL cholesterol (HDL-C) levels or hyperalphalipoproteinemia (HA). Premature CHD was observed in FH individuals without HA. The study of this family established that the HA trait in the family also followed an autosomal dominant mode of inheritance with a pattern of segregation independent from FH. We identified a locus on chromosome 6 linked to elevated HDL-C levels (HA) in this family. Haplotype analysis refined the localization to a 7.32-cM interval (73 to 80 cM from pter) flanked by markers D6S1280 and D6S1275. Parametric 2-point and multipoint analyses yielded maximum LOD scores of 3.05 and 3.17, respectively. This finding was confirmed with a nonparametric multipoint score of 3.78 (P=0.0009). We propose that this locus, linked to elevated HDL-C levels, confers protection against premature CHD within an FH context.

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• Characterization of a naturally occurring new version of the cholesterol ester transfer protein (CETP) from small intestine.

  Authors: Ana L Alonso, Alejandro Zentella-Dehesa, Jaime Mas-Oliva

  Molecular and cellular biochemistry. 04/2003; 245(1-2):173-82.

  The cholesterol ester transfer protein (CETP) is found in plasma mediating the transfer of cholesterol esters and triacylglycerides between lipoproteins. The last 26 amino acids of its carboxy-endThe cholesterol ester transfer protein (CETP) is found in plasma mediating the transfer of cholesterol esters and triacylglycerides between lipoproteins. The last 26 amino acids of its carboxy-end correspond to an amphipathic a-helix whose hydrophobic side has been directly involved in the transfer of lipids. Alterations in this region lead to the reduction or loss of lipid transfer activity. To date, the only variant of the CETP messenger that has been reported lacks exon 9, which translates into an inactive isoform regarding neutral lipid transfer. In this study, we describe a new version of the messenger RNA of rabbit CETP identified exclusively in the small intestine of wild type (WT) rabbits. This isoform includes several of the intron bases prior to exon 16. The presence of a stop codon within this sequence prevents translation of exon 16, substituting the original carboxy-end sequence and therefore generating a random structure that does not contain the region responsible for neutral lipid transfer. Antibodies generated against a peptide within the carboxy-end sequence of the new isoform show the presence of this new protein in human plasma.

• NF-kappaB dependent activation of human endothelial cells treated with soluble products derived from human lymphomas.

  Authors: Adriana Estrada-Bernal, Criselda Mendoza-Milla, José Luis Ventura-Gallegos, Lucia Nikolaia López-Bojórquez, Enrique Miranda-Peralta, Fabián Arechavaleta-Velasco, Felipe Vadillo-Ortega, Luis Sánchez-Sánchez, Alejandro Zentella-Dehesa

  Cancer letters. 04/2003; 191(2):239-48.

  Nuclear factor of the Immunoglobulin Kappa chain of B cells (NF-kappaB) activation is an early event during cytokine-mediated endothelial activation related to increased adhesion of leucocytes. WeNuclear factor of the Immunoglobulin Kappa chain of B cells (NF-kappaB) activation is an early event during cytokine-mediated endothelial activation related to increased adhesion of leucocytes. We report that soluble products secreted by two human lymphomas activate NF-kappaB, and increase the ability of endothelial cells to adhere U937 cells in vitro. Analysis of the tumor-derived products revealed the absence of tumor necrosis factor-alpha and interleukin-1beta. Interference of NF-kappaB activation prevented the increase in U937 cell adhesion, suggesting a potential role for endothelial NF-kappaB activation in the establishment of physical interactions between the vascular endothelium and tumor cells.

• Molecular mechanisms involved in the pathogenesis of septic shock.

  Authors: Lucia Nikolaia López-Bojórquez, Alejandro Zentella-Dehesa, Gustavo Reyes-Terán

  Archives of medical research. 35(6):465-79.

  Pathogenesis of the development of sepsis is highly complex and has been the object of study for many years. The inflammatory phenomena underlying septic shock are described in this review, as wellPathogenesis of the development of sepsis is highly complex and has been the object of study for many years. The inflammatory phenomena underlying septic shock are described in this review, as well as the enzymes and genes involved in the cellular activation that precedes this condition. The most important molecular aspects are discussed, ranging from the cytokines involved and their respective transduction pathways to the cellular mechanisms related to accelerated catabolism and multi-organic failure.