Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Previous work has shown that the diabetogenic action of streptozotocin is reduced in rats adapted to a high-protein, carbohydrate-free diet and that plasma valine, leucine and isoleucine concentrations are markedly elevated in rats adapted to the high-protein diet. 2. To test the possibility that these branched-chain amino acids play a role in the beneficial effects of the high-protein diet, rats fed the control balanced diet were injected intraperitoneally with mixtures of valine, leucine and isoleucine (0.25 or 0.50 g/kg body weight of each amino acid), or with each of these amino acids separately (0.50 g/kg), 15 min before streptozotocin administration (40 mg/kg, intravenously). Arginine (0.50 g/kg) was administered in one experiment. Control animals received equal volumes of saline. 3. Rats previously injected with the amino acid mixtures showed a partial but significant reduction of diabetes severity as indicated by lower plasma glucose levels, higher rates of body weight gain and greater amounts of epididymal and retroperitoneal fat. No protection was observed after the administration of either valine, isoleucine, leucine or arginine. 4. These data suggest that the elevated levels of plasma branched-chain amino acids may account at least in part for the initial protective effect of high-protein diets against streptozotocin beta-cytotoxicity when the cells are first exposed to the drug.
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PMID:Administration of branched-chain amino acids reduces the diabetogenic effect of streptozotocin in rats. 296 88

Three factors were studied for their effects on the first cleavage division of in vitro fertilized hamster eggs. Eggs from superovulated females were inseminated with precapacitated epididymal hamster sperm in medium containing either fatty acid-free (FAF) or fraction V (V) bovine serum albumin (BSA), in the presence or absence of cumulus cells. After incubation for 3 to 4 h with sperm, eggs were transferred to culture medium containing FAF- or V-BSA, with or without amino acids (glutamine, isoleucine, methionine, and phenylalanine), and the percentages of eggs cleaving to two cells were recorded after a further 20 h of incubation. Fatty acid-free BSA was found to support a significantly higher percentage of eggs cleaving than V-BSA and was used in all further experiments. The presence of cumulus cells during fertilization was found to have a beneficial effect on cleavage when no amino acids were added to the culture medium, but when amino acids were included, eggs fertilized with or without cumulus present cleaved equally well. These results represent another step toward defining the optimal environmental conditions for obtaining the first cleavage division of hamster eggs in vitro.
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PMID:The effects of amino acids, cumulus cells, and bovine serum albumin on in vitro fertilization and first cleavage of hamster eggs. 668 53

The effect of amino acids on insulin responsiveness in epididymal adipose tissue was examined. It was found that insulin-stimulated glucose oxidation in fat cells was significantly inhibited by glycine, alanine, valine, leucine, isoleucine, cysteine, methionine, lysine, phenylalanine, and proline. The effect of insulin on glucose incorporation into triglyceride is also severely diminished by these amino acids. In addition, alanine reduced the incorporation of precursors ([U-14C]glucose or [1-14C]palmitate) into triglyceride both in vitro and in vivo. The Ki values of alanine were 0.4 and 0.5 mM toward the precursors of glucose and palmitate, respectively. The mechanism of reduction of insulin responsiveness in rat adipose tissue is discussed on the basis of these results.
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PMID:Effect of amino acids on insulin-stimulated glucose metabolism in fat cells. 701 47

The synthetic C-terminal peptide fragment of human growth hormone, Leu-Arg-Ile-Val Gln-Cys-Arg-Val-Ser-Glu-Gly-Ser-Cys-Gly-Phe (hGH 177-191), was shown to have antilipogenic activity identical with that of the intact molecule of human growth hormone (hGH). No significant lipolytic effect of hGH 177-191 was found as determined by the rate of glycerol release from epididymal fat pads of the peptide-treated rats. The results support the suggestion that the functional domain responsible for the antilipogenic activity of hGH resides in the C-terminal region of the molecule and that the main physiological effect of hGH in lipid metabolism is at the level of lipogenesis.
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PMID:Antilipogenic action of synthetic C-terminal sequence 177-191 of human growth hormone. 835 31

Cyclic AMP-dependent protein kinase (PKA) is anchored at specific subcellular sites through the interaction of the regulatory subunit (R) with protein kinase A-anchoring proteins (AKAPs) via an amphipathic helix binding motif. Synthetic peptides containing this amphipathic helix domain competitively disrupt PKA binding to AKAPs and cause a loss of PKA modulation of cellular responses. In this report we use S-Ht31, a cell-permeant anchoring inhibitor peptide, to study the role of PKA anchoring in sperm. Our analysis of three species of mammalian sperm detected three isoforms of PKA (RIIalpha, RIIbeta, and RIbeta) and one 110-kDa AKAP. The addition of S-Ht31 to bovine caudal epididymal sperm inhibits motility in a time- and concentration-dependent manner. A control peptide, S-Ht31-P, identical to S-Ht31 except for a proline for isoleucine substitution to prevent amphipathic helix formation, had no effect on motility. The inhibition of motility by S-Ht31 is reversible but only if calcium is present in the suspension buffer, suggesting a role for PKA anchoring in regulating cellular calcium homeostasis. Surprisingly, inhibition of PKA catalytic activity had little effect on basal motility or motility stimulated by agents previously thought to work via PKA activation. These data suggest that the interaction of the regulatory subunit of PKA with sperm AKAPs, independent of PKA catalytic activity, is a key regulator of sperm motility and that disruption of this interaction using cell-permeable anchoring inhibitor peptides may form the basis of a sperm-targeted contraceptive.
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PMID:Protein kinase A-anchoring inhibitor peptides arrest mammalian sperm motility. 903 May 27

Using mechanical and chemical dissection methods, fibrous sheath was isolated both from normal ejaculated human spermatozoa and from rabbit cauda epididymal spermatozoa. The same techniques did not produce a pure preparation of fibrous sheath from ejaculated rabbit spermatozoa, suggesting that further cross-linking and stabilization of sperm structures occurs in response to components of the seminal plasma. The isolation procedures were monitored by phase contrast microscopy and the purity of the fibrous sheath was verified by electron microscopy. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of isolated human fibrous sheath revealed at least 14 protein bands of which the most intensely stained were of molecular weight 84, 72, 66.2, 57, 32 and 28.5 kDa. The rabbit fibrous sheath revealed at least 10 protein bands, of which the most intensely stained were 35.2, 32.7 and 28.5 kDa. The amino acid composition of the purified fibrous sheath from human and rabbit spermatozoa was similar, being high in aspartic acid and/or asparagine and glutamic acid and/or glutamine, serine, alanine, leucine, lysine and glycine, but low in histidine, tyrosine and isoleucine. This composition is similar to that reported for the rat and suggests that mammalian sperm tail fibrous sheaths are composed of similar types of proteins, although there are apparent differences in protein components between species.
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PMID:Isolation and characterization of human and rabbit sperm tail fibrous sheath. 923 58

To identify a novel candidate(s) for acrosomal proteins that act on the sperm/egg interaction, a DNA fragment was PCR-amplified from a cDNA library of acrosin-deficient mouse testis and then used as a probe to screen a mouse testis cDNA library. Complementary DNA clones encoding each of two similar but different serine proteases, TESP1 and TESP2, have been identified. The nucleotide sequences of these clones indicate that mouse TESP1 and TESP2 are initially synthesized as preproproteins of 367 and 366 amino acids, respectively. Comparison of the two TESP sequences with those of typical serine proteases suggests that each TESP zymogen is probably converted into a two-chain mature enzyme consisting of light and heavy chains covalently linked by a single pre-existing disulfide bond. The conversion may be accomplished by another protease(s) with a trypsin-like cleavage specificity, since it is unlikely that the mature TESP1 and TESP2 are capable of splitting the Lys-Ile bond between the light and heavy chains. Northern blot analysis of total cellular RNA demonstrates that the TESP1 and TESP2 genes are expressed only in the testis, and the transcripts are abundantly present in the haploid round spermatids. Moreover, immunocytochemical analysis of mouse cauda epididymal sperm using affinity-purified antibodies reveals that these two TESPs are both localized in the sperm acrosome and are released during the acrosome reaction induced by calcium ionophore A23187. These findings provide additional clues for elucidating the mechanisms involved in the sperm/egg interactions, including penetration of the zona pellucida by sperm.
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PMID:Two novel testicular serine proteases, TESP1 and TESP2, are present in the mouse sperm acrosome. 958 71

The 94-kDa ram epididymal fluid form of the sperm membrane-derived germinal angiotensin I-converting enzyme (ACE) was purified by chromatography, and some of its enzymatic properties were studied. For the artificial substrate furanacryloyl-L-phenylalanylglycylglycine (FAPGG), the enzyme exhibited a Michaelis constant (K(m)) of 0.18 mM and a V(max) of 34 micromoles/(min x mg) and for hippuryl-L-histidyl-L-leucine a K(m) of 2.65 mM and a V(max) of 163 micromoles/(min x mg) under the defined standard conditions (300 mM NaCl and 50 mM Tris; pH 7.5 and 8.3, respectively). The FAPGG hydrolysis was decreased by 82.5% and 67.5% by EDTA and dithioerythritol, respectively, and was totally inhibited by specific ACE inhibitors such as captopril, P-Glu-Trp-Pro-Arg-Pro-Glu-Ile-Pro-Pro, and lisinopril. Optimum activity for FAPGG was with pH 6.0, 50 mM chloride, and 500 microM zinc. Under the various conditions tested, bradykinin, angiotensin (Ang) I, Ang II, and LHRH were competitors for FAPGG. Bradykinin and angiotensin I were the best competitors. The enzyme cleaved Ang I into Ang II, and the optimal conditions were with pH 7.5 and 300 mM chloride. The relationship between the carboxypeptidase activity in seminal plasma and the prediction of fertility of young rams was also studied. These results indicated a correlation between sperm concentration and ACE activity in semen but showed no statistically significant correlation between such activity and fertility of the animal. Finally, we tested the role of ACE in fertilization; no difference in the in vitro fertilization rate was observed in the presence of 10(-4) M captopril.
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PMID:Physiological and enzymatic properties of the ram epididymal soluble form of germinal angiotensin I-converting enzyme. 1167 47

Age-related hypertrophy of adipose tissue has been associated with a significant decrease in the number of angiotensin II receptors. The aim of this study was to investigate the characteristics of angiotensin II receptors in hypertrophic adipose tissue in animal obesity model using rats postnatally treated with monosodium glutamate. Angiotensin II is known to induce hypertrophy in several tissues of the cardiovascular system and might do the same in fat tissue. The expression and binding properties of angiotensin II AT(1) receptors in epididymal fat tissue of adult rats were studied using membrane-binding, RT-PCR, and immunoblotting. The amount of AT(1) receptor mRNA did not differ significantly between obese and control rats. Despite that glutamate-treated rats displayed approximately 4-times more AT(1) receptor immunoreactive protein content in fat tissue cell membranes than the controls did. In contrast, binding experiments showed a significant (40.3 +/- 6.2 %) decrease of (125)I-Sar(1)-Ile(8)-angiotensin II-binding to fat tissue cell membranes in obese rats compared to controls. In conclusion, the present study provides evidence for the low binding properties associated with an accumulation of AT(1) receptor protein in cell membranes of the fat tissue of rats with glutamate-induced obesity. Discrepancies among angiotensin II-binding, AT(1) receptor protein, and AT(1) receptor mRNA levels indicate a possible defect in the receptor protein, which remains to be identified. The results obtained support a role of angiotensin II and AT(1) receptors in the pathogenesis of obesity.
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PMID:Elevated AT1 receptor protein but lower angiotensin II-binding in adipose tissue of rats with monosodium glutamate-induced obesity. 1175 55

In this study, we investigated the effects of the branched-chain amino acid l-isoleucine (Ile) on both obesity and glucose/fat homeostasis in mice that were fed a high-fat (45% energy) diet. The mice were divided into different treatment groups and given a high-fat diet for 6 wk. During the last 4 wk, Ile was dissolved and added to the drinking water to a final concentration of 2.5%. The control mice received vehicle alone. The mice in the Ile group had an almost 6% lower body weight gain and 49% less epididymal white adipose tissue (WAT) mass with the control group (P < 0.05). The hepatic and skeletal muscle triglyceride (TG) concentrations and degree of hyperinsulinemia in the Ile group mice were also lower than the control group by 38, 47, and 39%, respectively (P < 0.05). The WAT leptin concentration was also lower, whereas that of adiponectin was higher, in the Ile group compared with the control group (P < 0.05). The hepatic levels of protein CD36/fatty acid translocase, PPARalpha, and uncoupling protein (UCP) 2 and the levels of UCP3 in skeletal muscle were all greater in the Ile group than in the control mice (P < 0.05). These results demonstrate that the liver and muscle TG concentrations are both lowered by Ile treatment. In addition, the PPARalpha and UCP expression levels in the mouse tissues were greater in the Ile group compared with the controls. Our current data thus suggest that supplementation with Ile might be useful in the treatment of metabolic syndrome.
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PMID:Isoleucine prevents the accumulation of tissue triglycerides and upregulates the expression of PPARalpha and uncoupling protein in diet-induced obese mice. 2008 73


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