Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seminiferous peritubular cells have previously been shown to secrete a protein termed P-Mod-S which modulates the functions of Sertoli cells. The present study provides an initial characterization of P-Mod-S and examines the actions of P-Mod-S on Sertoli cells. Gel filtration chromatography demonstrates that P-Mod-S has an apparent molecular weight of 70 000 that could not be dissociated to a lower molecular weight form. A 40- to 90-fold purification of P-Mod-S was obtained with a predicted half maximal effective concentration for Sertoli cells of less than 10(-9) M. Through an analysis of the actions of P-Mod-S on Sertoli cells it is demonstrated that P-Mod-S stimulates the Sertoli cell to a greater extent than any single hormone or vitamin known to influence the cell. P-Mod-S maximally stimulates testicular transferrin and androgen-binding protein production by Sertoli cells, but does not stimulate levels of plasminogen activator activity. P-Mod-S also appears to induce the synthesis of several proteins that are not detected in control non-treated Sertoli cell cultures. One such protein whose synthesis was stimulated by P-Mod-S treatment of Sertoli cells was a component having a molecular mass of 20 kDa. This 20 kDa Sertoli cell-secreted protein was specifically immunoprecipitated with an antibody against an epididymal lactalbumin-like protein. This implies that P-Mod-S can induce Sertoli cells to synthesize and secrete a lactalbumin-like protein. P-Mod-S was found not to contain mitogenic activity. Data presented indicate that testicular peritubular cells synthesize and secrete a 70 kDa non mitogenic paracrine factor termed P-Mod-S which has a dramatic influence on Sertoli cell functions. Results are discussed with respect to modulation of epithelial (Sertoli) cell functions by components produced by mesenchymal (peritubular) cells.
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PMID:Identification of a non-mitogenic paracrine factor involved in mesenchymal-epithelial cell interactions between testicular peritubular cells and Sertoli cells. 308 88

The objective of this investigation was to evaluate histologically and pathologically the effect of long-term sustained release of D and DHT on the reproductive system of male rats. A total of 120 Sprague-Dawley male albino rats were distributed equally into three groups. Two CDD, one nonimpregnated and the other impregnated with PLA, were implanted in each rat in groups I and II. Capsules implanted in group I rats were loaded with 20 mg DHT and 20 mg D each. Group II rats were implanted with two empty capsules (sham group), and group III animals served as unimplanted controls. Blood samples were withdrawn weekly via tail artery from all animals. Eight rats from each group were euthanized at the end of the one, three, six, nine, and twelve months following the implantation of the devices. No significant changes in the weights of vital (spleen, kidneys, heart, adrenals, lungs) organs of rats were observed among any of the three different groups. Vas deferens and epididymal fluid were devoid of normal spermatozoa within three months of implanting the D+DHT containing devices. Testes weights decreased significantly in the rats implanted with CDD containing D+DHT and the seminiferous tubules became oligospermic after one month and azoospermic after three months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pathophysiological evaluation associated with sustained delivery of danazol and dihydrotestosterone in adult male rodents. 794 36

Epididymis is a site of sperm maturation and storage. Limited and directed-proteolysis regulated by plasminogen activator (PA), plasminogen activator inhibitor type-1 (PAI-1) and other related factors may play an essential role in these processes. Our previous studies have demonstrated that rat epididymis expressed luteinizing hormone receptor (LHR), tissue type (t) and urokinase type (u)PA, mRNAs, and tPA activity was stimulated in vitro by human chorionic gonoadotrophin (HCG). In the present study we further examined localization of mRNAs for tPA, uPA, LHR, androgen receptor (AR), as well as inhibin subunits alpha, betaA and betaB in rhesus monkey epididymis. Using in-situ hybridization with digoxygenin-labelled cRNA probes, we have demonstrated that tPA and PAI-1 mRNAs were localized in epithelial cells of adult monkey epididymis. uPA mRNA was localized in the same areas, but to a much smaller extent. tPA, uPA and PAI-1 mRNAs were greatly expressed in the caput and corpus of adult epididymis than in other regions. In-vitro experiments showed that both tPA and uPA activities in epididymal cells were dramatically stimulated by HCG, but not by follicle stimulating hormone (FSH). LHR (but not FSH receptor) and AR mRNAs were localized in the epithelial cells of the epididymis. However, LHR mRNA was detected in both adult and immature infant monkeys, whereas AR was found only in the adult. Inhibin alpha, betaA and betaB mRNAs were also detected in this organ, betaA mRNA being more strongly expressed in the caput than in other regions of the epididymis. We suggest that LH and androgen may be the key hormones in coordination with the PA-PAI-1 system in regulating epididymal differentiation and sperm maturation.
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PMID:Localization of plasminogen activator and inhibitor, LH and androgen receptors and inhibin subunits in monkey epididymis. 943 19

Extraction with Tris-citrate or Tris-NaCl-EGTA improved the yield of phospholipase A2 (PLA2) from ram semen by 40-50 fold over the previously recommended method of extraction by dilute (0.18 N) sulphuric acid. The enzyme activity in the citrate extract deteriorated more rapidly than in Tris-NaCl-EGTA. The semen PLA2 activity was optimum at pH 8.0, heat sensitive at 70 degrees C for 30 min, activated by Ca2+ (although approximately 60% activity was also found in the absence of calcium) and did not exist as a pro-enzyme. The semen PLA2 activity was equally distributed among the sperm and seminal plasma (SP) components of ram semen. However, the low levels of PLA2 activity in the SP of vasectomised rams tend to suggest that PLA2 in the SP fraction may have originated from testicular or epididymal secretions or leakage, from sperm. PLA, in sperm exists as a large molecular weight aggregate, whereas in SP it is present as a smaller aggregate. In addition to PLA2, semen also contained PLA2 inhibitor activities. Inhibition was observed against PLA2s from bee venom, pig pancreas and oviductal extracts. The inhibitory activity is presumed to be due to a large molecular weight protein as the inhibitor activity was not extracted in a chloroform:methanol (2:1; v/v) mixture, it was non-dialysable, precipitated by 10% trichloroacetic acid and destroyed by proteases. The inhibitor activity was distributed in various molecular weight fractions of sperm, SP and SP from vasectomised rams.
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PMID:Studies on the measurement of phospholipase A2 (PLA2) and PLA2 inhibitor activities in ram semen. 1046 98

The involvement of Ca(2+) sensitization mediated through Rho kinase in the contractility of rat epididymal vas deferens was investigated using Rho kinase inhibitors, trans-4-[(1R)-1-aminoethyl]-N-4-pyridinilcyclohexanecarboxamide dihydrochloride (Y-27632) and 1-(5-isoquinolinesulphonyl)homopiperazine (HA 1077), in comparison with myosin light chain kinase (MLCK) inhibitors, wortmannin and 1-(5-chloronaphthalenesulphonyl)homopiperazine (ML-9) and agents that affect protein kinase C (PKC) and non-receptor tyrosine kinase intracellular signalling. 2 In Ca(2+)-free/ethyleneglycol-bis-(beta-aminoethylether)N,N,N('),N(')-tetraacetic acid (EGTA) (1 mM) medium, noradrenaline evoked sustained contractions. Y-27632 and HA 1077 caused a concentration-dependent inhibition and complete relaxation (IC(50), 1.08 and 1.75 microM respectively). The Ca(2+)-free contraction was reduced by wortmannin (10 microM) or ML-9 (10 microM) but not by inhibitors of diacylglycerol metabolism, 3-[2-[4[bis(4-Fluoropheny)methylene]-1-piperidinyl]-2,3-dihydro-2-thioxi-4(H)-quinazolinone (R59949) (10 microm) or 1,6-bis(cyclohexyloximinocarbonylamino)hexane (RHC-80267) (10 microM) or by the phospholipase A(2) (PLA(2)) inhibitor, quinacrine (up to 100 microM) or tyrosine kinase inhibitor, genistein (30 microM). 3 In the presence of Ca(2+) (2.5 mM), noradrenaline (100 microM) evoked rhythmic activity and biphasic tonic contractions. Y-27632 (1-10 microM) or HA 1077 (1-10 microM) reduced the amplitude of rhythmic activity and tonic contractions. ML-9 (10 microM) attenuated the occurrence of rhythmic activity and modestly reduced the tonic contractions. ML-9 (10 microM) combined with Y-27632 (10 microM) significantly reduced the tonic contractions. ML-9 (30 microM) alone (or combined with Y-27632 10 microM) suppressed the rhythmic activity and substantially reduced (or abolished) the tonic contractions. 4 Contractions evoked by high [K(+)](o) (120 mM) or alpha,beta-methylene ATP (10 microM) were reduced significantly by Y-27632 (1-3 microM) indicating that the Rho kinase signalling pathway is activated by direct tissue depolarization or by stimulation of ligand-gated P(2X) purinoceptors. 5 Collectively, these results indicate that Ca(2+)-sensitization mediated by Rho kinase is involved in agonist- or depolarization-induced contraction of rat epididymal vas deferens. It is the major contractile mechanism underlying noradrenaline-induced Ca(2+)-free responses. It contributes to Ca(2+)-dependent rhythmic contractility and optimizes the development of full contractile tension triggered through calmodulin/MLCK activation by stimulated influx of Ca(2+).
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PMID:Attenuation of contractility in rat epididymal vas deferens by Rho kinase inhibitors. 1655 45

We previously reported that accessory sex gland fluid (AGF) from high fertility (HF) bulls influenced the oocyte-penetrating capacity of cauda epididymal sperm from low fertility (LF) bulls, based on in vitro fertilization (IVF) assays. The present study determined if AGF proteins were associated with these effects. Nineteen IVF assays with 12 bulls were grouped as follows. Group I (n = 8): assays where sperm from LF bulls exposed to AGF from HF bulls had greater oocyte penetration than exposed to homologous AGF. Group II (n = 7): sperm from LF bulls to AGF from HF bulls versus homologous AGF showed no significant differences. Group III (n = 4): sperm from LF bulls treated with homologous AGF had greater fertility than sperm treated with AGF from HF bulls. Sire fertility was based on nonreturn rates (NNR) and AGF collected by artificial vagina from bulls with cannulated vasa deferentia. Two-dimensional SDS-PAGE maps of AGF were analyzed by PDQuest and proteins identified by tandem mass spectrometry and Western blots. Differences in spot intensity between AGF of HF and LF bulls were compared across groups of IVF assays (P < 0.05). The expression of BSP A1/A2 and A3, BSP 30 kDa, clusterin, albumin, phospholipase A(2) (PLA(2)), and osteopontin was greater in the AGF of HF bulls in Group I as compared to Groups II and III. Conversely, there was less nucleobindin in the AGF of HF bulls in Group I than in Groups II and III. This is the first report of nucleobindin (58 kDa/pI 5.6) in male reproductive fluids, using both immunoblots and mass spectrometry. Thus, the effect of AGF from HF bulls on epididymal sperm is likely the result of specific proteins expressed in the AGF.
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PMID:Proteins of the accessory sex glands associated with the oocyte-penetrating capacity of cauda epididymal sperm from holstein bulls of documented fertility. 1694 73

Prostaglandin (PG) E(2) is considered to participate in the storage of fat in adipocytes and hepatocytes, but roles of group IVA phospholipase A(2) (PLA(2)), a key PLA(2) isozyme in the arachidonic acid cascade, remain unclear. The present study examined the possible involvement of the enzyme using group IVA PLA(2)-deficient mice (C57BL/6 background, 22 weeks of age) fed a normal diet (5.3% fat). The ratio of epididymal fat pad weight to body weight was significantly reduced in group IVA PLA(2)-deficient mice compared to wild-type mice. Histological analysis revealed that in group IVA PLA(2)-deficient mice, the adipocytes were smaller, and hepatocytes bearing cytoplasmic vacuolation were scarce. Hepatic triglyceride content and the serum levels of PGE(2) in the deficient mice were also lower. However, there was no difference in the serum levels of insulin, glucose, non-esterified free fatty acid, or total cholesterol between the deficient and wild-type mice. Our findings suggest that group IVA PLA(2) is involved in the storage of lipids in the adipose tissue and liver and in determining circulating PGE(2) levels.
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PMID:Group IVA phospholipase A2 is associated with the storage of lipids in adipose tissue and liver. 1828 78

Hepatic fat deposition with hepatocellular damage, a feature of non-alcoholic fatty liver disease, is mediated by several putative factors including prostaglandins. In the present study, we examined whether group IVA phospholipase A(2) (IVA-PLA(2)), which catalyzes the first step in prostanoid biosynthesis, is involved in the development of fatty liver, using IVA-PLA(2)-knockout mice. Male wild-type mice on high-fat diets (20% fat and 1.25% cholesterol) developed hepatocellular vacuolation and liver hypertrophy with an increase in the serum levels of liver damage marker aminotransferases when compared with wild-type mice fed normal diets. These high-fat diet-induced alterations were markedly decreased in IVA-PLA(2)-knockout mice. Hepatic triacylglycerol content was lower in IVA-PLA(2)-knockout mice than in wild-type mice under normal dietary conditions. Although high-fat diets increased hepatic triacylglycerol content in both genotypes, the degree was lower in IVA-PLA(2)-knockout mice than in wild-type mice. Under the high-fat dietary conditions, IVA-PLA(2)-knockout mice had lower epididymal fat pad weight and smaller adipocytes than wild-type mice. The serum level of prostaglandin E(2), which has a fat storage effect, was lower in IVA-PLA(2)-knockout mice than in wild-type mice, irrespective of the kind of diet. In both genotypes, high-fat diets increased serum leptin levels equally between the two groups, but did not affect the serum levels of adiponectin, resistin, free fatty acid, triacylglycerol, glucose, or insulin. Our findings suggest that a deficiency of IVA-PLA(2) alleviates fatty liver damage caused by high-fat diets, probably because of the lower generation of IVA-PLA(2) metabolites, such as prostaglandin E(2). IVA-PLA(2) could be a promising therapeutic target for obesity-related diseases including non-alcoholic fatty liver disease.
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PMID:Alleviation of high-fat diet-induced fatty liver damage in group IVA phospholipase A2-knockout mice. 1995 52

SERPINE2, one of the potent serine protease inhibitors that modulates the activity of plasminogen activator and thrombin, is implicated in many biological processes. In the present study, we purified SERPINE2 from mouse seminal vesicle secretion (SVS), using liquid chromatography and identified it by liquid chromatography/tandem mass spectrometry, and it showed potent inhibitory activity against the urokinase-type plasminogen activator. SERPINE2 was expressed predominantly in seminal vesicles among murine male reproductive tissues. It was immunolocalized to the SVS and mucosal epithelium of the seminal vesicle, epididymis, coagulating gland, and vas deferens. In the testes, SERPINE2 was immunostained in spermatogonia, spermatocytes, spermatids, Leydig cells, and spermatozoa. SERPINE2 was also detected on the acrosomal cap of testicular and epididymal sperm and was suggested to be an intrinsic sperm surface protein. The purified SERPINE2 protein could bind to epididymal sperm. A prominent amount of SERPINE2 was detected on ejaculated and oviductal spermatozoa. Nevertheless, SERPINE2 was detected predominantly on uncapacitated sperm, indicating that SERPINE2 is lost before initiation of the capacitation process. Moreover, SERPINE2 could inhibit in vitro bovine serum albumin-induced sperm capacitation and prevent sperm binding to the egg, thus blocking fertilization. It acts through preventing cholesterol efflux, one of the initiation events of capacitation, from the sperm. These findings suggest that the SERPINE2 protein may play a role as a sperm decapacitation factor.
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PMID:SERPINE2, a serine protease inhibitor extensively expressed in adult male mouse reproductive tissues, may serve as a murine sperm decapacitation factor. 2108 13