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A Rascón

Publications and source records attributed to A Rascón.

10 recordsLinked to original sources
PubMed1997

[Cyclic nucleotide phosphodiesterases: diversity, classification, structure and function].

During the last years there have been major advances in the knowledge of cyclic nucleotide phosphodiesterases. Particularly, referred to the presence of multiple different isozymes. Seven different phosphodiesterase gene families, have been described in mammalian tissues, containing several distinct genes, most of them expressed in different tissues as functionally unique splice variants. This article includes various aspects of the currently accepted nomenclature, structure and function of each family of phosphodiesterases. Finally, a brief discussion of the presence and role of these enzymes in the cell proliferation and differentiation processes, in parasites of the Trypanosmatidae family, is provided.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1994

Identification of the phosphorylation site in vitro for cAMP-dependent protein kinase on the rat adipocyte cGMP-inhibited cAMP phosphodiesterase.

Rat adipocyte cGMP-inhibited cAMP phosphodiesterase (cGI-PDE) appears to be dually regulated in intact cells by serine phosphorylations induced by isoprenaline and insulin, respectively (Degerman, E., Smith, C. J., Tornqvist, H., Vasta, V., Belfrage, P., and Manganiello, V. C. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 533-537; Smith, C. J., Vasta, V., Degerman, E., Belfrage, P., and Manganiello, V. C. (1991) J. Biol. Chem. 266, 13385-13390). Since cAMP-dependent protein kinase (cAMP-PK) catalyzes the beta-adrenergic effects, the site in the isolated cGI-PDE phosphorylated by this kinase was explored. A peptide, LRRSSGASGLLTSEHHSR (P18), corresponding to the amino acid sequence Leu423-Arg440 in the putative regulatory domain of the rat adipocyte cGI-PDE was synthesized. It contains a consensus substrate sequence -RRXS- for cAMP-PK within two tryptic cleavage sites and was readily phosphorylated by cAMP-PK. Two phosphopeptides, identified as RS-[32P]SGASGLLTSEHHSR and S-[32P]SGASGLLTSEHHSR, were obtained after stoichiometric phosphorylation and trypsinization of the peptide. These two peptides and the two main tryptic phosphopeptides obtained from immunoisolated [32P]cGI-PDE phosphorylated with cAMP-PK in a solubilized crude adipocyte membrane fraction were immuno-precipitated by an affinity-purified polyclonal antibody raised against P18 and exhibited the same chromatographic and electrophoretic profiles in three different separation systems. Similar radiosequencing profiles indicated that the second most N-terminal serine, corresponding to Ser-427 in the intact cGI-PDE, was phosphorylated by cAMP-PK in both P18 and authentic cGI-PDE. It is concluded that serine 427 is the target for cAMP-PK phosphorylation of the rat adipocyte cGI-PDE in vitro.

Adipocytes↗
PubMed1994

Single-step affinity purification, partial structure and properties of human platelet cGMP inhibited cAMP phosphodiesterase.

The human platelet cilostamide- and cGMP-inhibited cAMP phosphodiesterase (cGI-PDE) was rapidly purified approximately 19,000-fold to apparent homogeneity using single step affinity chromatography on the isothiocyanate derivative of cilostamide coupled to aminoethyl agarose. Within 24 h, 30 micrograms of enzyme protein was obtained from 20 ml of packed platelets. Vmax for cAMP and cGMP was 6.1 and 0.9 mumol/min per mg protein, respectively. Several polypeptides (110/105, 79, 62, 55/53 kDa) were identified after SDS-PAGE, all of which were immunologically related to cGI-PDE and represented approx. 5, 20, 50 and 20% of the total protein, respectively. Limited proteolysis of the cGI-PDE with chymotrypsin produced a major fragment of approximately 47 kDa (and at least two smaller peptides) with catalytic activity and sensitivity to cGMP and OPC 3911 similar to controls. Phosphorylation of the cGI-PDE by cAMP-dependent protein kinase (A-kinase) resulted in maximal incorporation of 0.6-1.8 mol of 32P/mol 110/105 and 79 kDa polypeptides; much lower and variable amounts of phosphate were incorporated into the 62 and 55/53 kDa polypeptides. After digestion of cGI-PDE with several proteinases a number of peptides were isolated and sequenced. Most of the peptide sequences obtained could be aligned within the carboxy terminal domain of the deduced sequence of the human cardiac cGI-PDE. These and other results suggest that the subunit size of the intact platelet cGI-PDE is 110 kDa and that proteolytic fragments of 79, 62 and 55/53 kDa are produced during purification. The smaller fragments (62 and 55/53 kDa) contain the catalytic domain; the larger fragments (110 and 79 kDa) also contain the regulatory domain with phosphorylation sites for A-kinase.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

Insulin induced phosphorylation and activation of the cGMP-inhibited cAMP phosphodiesterase in human platelets.

Insulin induced phosphorylation and activation of the cGMP inhibited cAMP phosphodiesterase (cGI-PDE) in human platelets were demonstrated after isolation of the enzyme with specific polyclonal cGI-PDE antibodies. The demonstration of this insulin effect required suppression of basal cGI-PDE phosphorylation, through the use of the protein kinase inhibitor H-7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine). The human platelet insulin receptor beta-subunit, previously identified as a 97 kDa polypeptide, was detected with the use of wheat germ agglutinin chromatography and anti-phosphotyrosine antibodies. These results suggest that insulin, through phosphorylation/activation of cGI-PDE, could decrease cAMP/cAMP dependent protein kinase (cAMP-PK) activity and thereby make the platelets more sensitive towards aggregating agents.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

Purification and properties of the cGMP-inhibited cAMP phosphodiesterase from bovine aortic smooth muscle.

Pure cGMP-inhibited cAMP phosphodiesterase (cGI-PDE) in micrograms quantities was isolated from bovine aortic smooth muscle after more than 5000-fold purification using DEAE ion-exchange and affinity chromatography with a derivative of the specific cGI-PDE inhibitor cilostamide conjugated as a ligand to aminoethyl agarose (CIT-agarose). The cGI-PDE, which constituted about half of the high affinity cAMP-PDE activity of a tissue homogenate, was identified with a 105-kDa protein on SDS-PAGE through use of antibodies towards the human platelet, bovine cardiac and bovine adipose tissue cGI-PDE in Western blot and immunoprecipitation/immunoinactivation analysis. As observed during purification of the enzyme from other tissues the enzyme protein was exquisitely sensitive to proteolytic nicking during purification, resulting in several 30-77-kDa polypeptide fragments. Rapid immunoprecipitation from fresh tissue extracts was the only was found to partially prevent the proteolysis. The native enzyme had apparent molecular sizes of approx. 100,000 or, mainly approx. 220,000 by gel chromatography, presumably indicating the presence of monomeric and dimeric forms. The enzyme hydrolyzed cAMP and cGMP with normal Michaelis-Menten kinetics with Km of 0.16 and 0.09 microM, respectively, with Vmax for hydrolysis of cAMP of 0.3 compared to 3.1 mumol/min per mg protein for cAMP. The enzyme was potently and selectively inhibited by cGMP (IC50 approximately 0.25 microM) and the cardiotonic/vasodilatory drugs OPC-3911 (a cilostamide derivative), milrinone and CI-930 (IC50 approximately 0.05, 0.40 and 0.25 microM, respectively). The cGI-PDE was phosphorylated by cAMP-dependent protein kinase as has been reported for the analogous enzymes in heart, adipose tissue and platelets. The identification of a cGI-PDE in the aortic smooth muscle and its inhibitor specificity is consistent with the hypothesis that inhibition of this enzyme is important in the mechanism through which these drugs produce vasorelaxation.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1991

Selective inhibition of cGMP-inhibited and cGMP-noninhibited cyclic nucleotide phosphodiesterases and relaxation of rat aorta.

In the supernatant (50,000 g, 1 hr) fraction from rat aortic smooth muscle homogenates, approximately 50% of total cAMPE PDE activity was inhibited by OPC 3911 (3 microM), while approximately 20% was inhibited by rolipram (30 microM). A cGMP-inhibited cyclic nucleotide phosphodiesterase (cGI-PDE) was further purified using DEAE chromatography followed by affinity chromatography on the N-(2-isothiocyanato)ethyl derivative of cilostamide conjugated to aminoethyl agarose (CIT-agarose). OPC 3911, CI-930, and milrinone, but not rolipram, were potent and selective inhibitors of this enzyme. The PDE-activity in the CIT-agarose flow through fraction (RI-PDE), however, was inhibited potently by rolipram, but not by cGMP, OPC 3911, CI-930 or milrinone. Functional studies showed that OPC 3911, CI-930, and milrinone were potent relaxants of contracted rat aorta. Rolipram had little relaxant effect. When OPC 3911 or milrinone was combined with rolipram more than additive effects on aortic relaxation and cAMP content were obtained. OPC 3911 combined with milrinone had only additive effects. These results demonstrate the presence of a cGI-PDE in rat aortic smooth muscle, and that inhibition of this isozyme may be of primary importance for the relaxant effects of OPC 3911, CI-930, and milrinone. A RI-PDE activity was also found, but it appeared to be less important for modulation of vascular tone unless the cGI-PDE was already inhibited. This may explain the synergistic relaxant effects observed when both PDE-isozymes were inhibited.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1985

Inhibition of trypsins and chymotrypsins from different animal species: a comparative study.

The effect of 3 purified trypsin inhibitors and 4 legume seed extracts on teh trypsins and chymotrypsins of the activated pancreata of 11 animal species, including man, was measured. The activation was performed by either homologous enterokinase or by bovine trypsin. Several trypsinogens were not activated by the latter. Rabbit trypsin was the most sensitive to all inhibitor preparations, while the human trypsin was the most resistant, except to the black bean extract. The response of the chymotrypsins was more variable and those of capybara and rabbit showed extreme sensitivity. Considerable differences between the extracts of black and white garden beans, both Phaseolus vulgaris, with respect to their reactivity toward different animal enzymes were detected. No relation between relative pancreas weight and susceptibility toward soybean trypsin inhibitor could be observed.

Animals↗
PubMedDate not supplied

Possible relationship between neurocysticercosis and hematological malignancies.

BACKGROUND: Previous studies have shown an increased frequency of chromosomal abnormalities in lymphocytes from animals and humans with cysticercosis. Some reports have suggested an association between cancer and cysticercosis. The aim of this study was to investigate the possible association between neurocysticercosis and cancer. METHODS: We designed a mortality rate study from the autopsy files of the Department of Pathology at the General Hospital of Mexico. A total of 1,271 autopsy files were reviewed. All files in which a malignant neoplasia was found during autopsy were selected as cases. Autopsies in which no malignant disease was found were used as controls. The odds ratio was determined between the frequency of neurocysticercosis in patients with any malignant neoplasia and that of the controls. RESULTS: Neurocysticercosis was more frequent in cases with malignant hematological diseases (MHD) than in controls (p = 0.01). The odds ratio for this association was 3.54, with 95% confidence interval from 1.17-9.79. CONCLUSIONS: Most human cancers arise from the interaction of a multiplicity of factors, including xenobiotics and endogenous constituents. Therefore, while it will be difficult to demonstrate that neurocysticercosis is a causal agent of malignant hematological diseases (MHD), it should be considered as a potential risk factor for cancer induction in countries where cysticercosis remains a public health problem.

Adolescent↗
PubMedDate not supplied

[Mortality by poisoning in children].

OBJECTIVE: To determine the standing of mortality by poisoning in children in the Mexican Republic, in the years from 1979-1994. MATERIAL AND METHODS: Secondary sources were employed. Analyzed variables were: age, sex, year, external cause of trauma and poisoning according to the 9th International Classification of Diseases: E850-E858, E860-E869 and E905. Tendencies by specific causes were analyzed with a Poisson regression model and relative risk by age, sex and district were obtained. RESULTS: A total of 11,272 children under 15 years of age were recorded. The main causes were poisoning and toxic reactions caused by venomous plants or animals (E905); accidental poisoning by household gas or carbon monoxide (E868); and accidental poisoning by other drugs (E858). The relative risk was highest in age group < 1 year; the values were RR 29.6, CI 95% 29.2-33.4; RR 3.47, CI 95% 2.86-4.22 and RR 31.86, CI 95% 24.8-40.9. Risk was similar for both sexes except for E905. The state of Aguascalientes consistently presented the highest risk values and the state of Nuevo Leon, the lowest. CONCLUSIONS: Poisoning is an important cause of child mortality. Considering that most of these deaths can potentially be prevented since they occur at home it is recommended that responsible adults can build protection into their environment and into the way society operates. Prevention should involve a multidisciplinary approach since the phenomenon has multiple causes and possible solutions.

Cause of Death↗