Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) produces atrophy, morphological changes, impaired spermatogenesis, and epididymal lesions in testis of experimental animals. The effects of TCDD administration to male rats on various parameters in the testes were examined. 2. Nine days after TCDD administration, significant decreases in body and testes weights occurred. However, the testes weight as a percent of body weight was higher in treated than control animals. 3. An increase in lipid peroxidation (content of thiobarbituric acid reactive substances) occurred in conjunction with the decrease in testicular weights. 4. TCDD administration produced a 3-fold increase in protein kinase C activity, small but significant decrease is superoxide dismutase and glutathione peroxidase activities, and no effect on catalase, glutathione reductase or glutathione S-transferase activities in the testes. 5. Nine days after treatment with TCDD, in the testes the iron content of whole tissue and cytosol increased while a decrease in microsomal iron was observed. The copper content of mitochondria and microsomes decreased with a corresponding increase in cytosol copper content. A small increase in the zinc content of whole testes occurred. 6. The data indicate that testicular atrophy due to TCDD may be associated with lipid mobilization and peroxidation.
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PMID:2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced alterations in lipid peroxidation, enzymes, and divalent cations in rat testis. 324 26

Glutathione S-transferases, a family of enzymes that catalyze the conjugation of glutathione to a variety of substrates, are present in rat epididymis. In order to study the hormonal regulation of these enzymes in this tissue, adult rats were orchidectomized and implanted with empty or androgen-filled polydimethylsiloxane capsules. Orchidectomy alone significantly decreased caput-corpus epididymal glutathione S-transferase activity toward 2 substrates, 1-chloro-2,4-dinitrobenzene and trans-4-phenylbut-3-en-2-one, but had no effect on transferase activity toward the third substrate, 1,2-dichloro-4-nitrobenzene. In contrast to these results, orchidectomy did not alter glutathione S-transferase activity towards these substrates in the cauda epididymidis. Androgen replacement with testosterone prevented the orchidectomy-induced decrease in caput-corpus glutathione S-transferase activity toward 1-chloro-2,4-dinitrobenzene and trans-4-phenylbut-3-en-2-one and had no effect on transferase activity toward 1,2-dichloro-4-nitrobenzene. The effects of 5 alpha-reduced metabolites of testosterone were also studied. Both dihydrotestosterone and 5 alpha-androstan-3 alpha, 17 beta-diol maintained caput-corpus glutathione S-transferase activity toward 1-chloro-2,4-dinitrobenzene, although a lower dose of dihydrotestosterone was sufficient; these 1 androgens were unable to maintain activity toward trans-4-phenylbut-3-en-2-one and caused a suprastimulation of activity toward 1,2-dichloro-4-nitrobenzene above control values. The third 5 alpha-reduced androgen studied, 5 alpha-androstan-3 beta, 17 beta-diol had no effect on the transferase activity toward any of the 3 substrates. These results demonstrate that the epididymal glutathione S-transferases are under separate control and are differentially regulated by testosterone and its 5 alpha-reduced metabolites.
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PMID:Regulation of epididymal glutathione S-transferases: effects of orchidectomy and androgen replacement. 708 27

Apical and narrow cells of the initial segment and intermediate zone of the adult rat epididymis were glutaraldehyde fixed and Epon embedded for routine light (LM) and electron (EM) microscopic analysis and Bouin fixed and paraffin embedded for LM immunocytochemical analysis in order to examine their structural features, distribution, and functions. The goblet-shaped apical cells comprised 10.7 +/- 1.0% of the total epithelial population in the proximal initial segment but only 1.3 +/- 0.5% in the intermediate zone. In the EM, these cells presented numerous mitochondria, few C-shaped vesicles, and a pale round or oblong nucleus located in the upper half of their cytoplasm. The slender elongated narrow cells increased from 2.8 +/- 0.3% in the proximal initial segment to 6.3 +/- 0.4% in the intermediate zone. In an EM analysis, these cells presented numerous C-shaped vesicles and mitochondria and a small flattened nucleus located in the upper half of their cytoplasm. The structural features of both these cell types differed not only from each other but also from the neighboring principal and basal cells of each region. Of the various antibodies examined to lysosomal proteins, narrow and apical cells expressed high levels of cathepsin D, while beta-hexosaminidase A was expressed at high levels in narrow cells but only moderately in apical cells. Apical cells were intensely reactive for the Yf subunit of glutathione S-transferase (GST)-P, whereas no reaction was seen in narrow cells; the Yo subunit of GST was localized within both cell types but only in the proximal initial segment. Narrow cells exclusively expressed carbonic anhydrase II. Selective differences in the immunolocalization of these various proteins were also noted between these two cell types and principal and basal cells. The localization of cathepsin D and beta-hexosaminidase A within narrow and apical cells suggests these cells may be involved in the degradation of specific proteins within their lysosomes, whereas the presence of GSTs may aid in protecting spermatozoa from a changing environment of harmful electrophiles. Localization of carbonic anhydrase II exclusively within narrow cells suggests that these cells may modify the pH of the lumen resulting in the quiescence of sperm motility in the proximal end of the epididymis. Together, the data indicate that apical and narrow cells differ not only from each other but also from principal and basal cells in their structure and relative distribution. They also express different proteins within the distinct epididymal regions, indicating that they perform different functions.
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PMID:Apical and narrow cells are distinct cell types differing in their structure, distribution, and functions in the adult rat epididymis. 879 11

Male weanling Wistar rats (n = 15), weighing 200-220 g, were allocated for 6 wk to diets containing 1% (by weight) of conjugated linoleic acid (CLA), either as the 9c,11 t-isomer, the 10t,12c-isomer, or as a mixture containing 45% of each of these isomers. The five rats of the control group received 1% of oleic acid instead. Selected enzyme activities were determined in different tissues after cellular subfractionation. None of the CLA-diet induced a hepatic peroxisome-proliferation response, as evidenced by a lack of change in the activity of some characteristic enzymes [i.e., acyl-CoA oxidase, CYP4A1, but also carnitine palmitoyltransferase-I (CPT-I)] or enzyme affected by peroxisome-proliferators (glutathione S-transferase). In addition to the liver, the activity of the rate-limiting beta-oxidation enzyme in mitochondria, CPT-I, did not change either in skeletal muscle or in heart. Conversely, its activity increased more than 30% in the control value in epididymal adipose tissue of the animals fed the CLA-diets containing the 10t,12c-isomer. Conversely, the activity of phosphatidate phosphohydrolase, a rate-limiting enzyme in glycerolipid neosynthesis, remained unchanged in adipose tissue. Kinetic studies conducted on hepatic CPT-I and peroxisomal acyl-CoA oxidase with CoA derivatives predicted a different channeling of CLA isomers through the mitochondrial or the peroxisomal oxidation pathways. In conclusion, the 10t,12c-CLA isomer seems to be more efficiently utilized by the cells than its 9c,11t homolog, though the Wistar rat species appeared to be poorly responsive to CLA diets for the effects measured.
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PMID:Effects of conjugated linoleic acid isomers on lipid-metabolizing enzymes in male rats. 1069 29

Male "viable motheaten" (me(v)) mice, with a naturally occurring mutation in the gene of the SH2 domain protein tyrosine phosphatase SHP-1, are sterile. Known defects in sperm maturation in these mice correlate with an impaired differentiation of the epididymis, which has similarities to the phenotype of mice with a targeted inactivation of the Ros receptor tyrosine kinase. Ros and SHP-1 are coexpressed in epididymal epithelium, and elevated phosphorylation of Ros in the epididymis of me(v) mice suggests that Ros signaling is under control of SHP-1 in vivo. Phosphorylated Ros strongly and directly associates with SHP-1 in yeast two-hybrid, glutathione S-transferase pull-down, and coimmunoprecipitation experiments. Strong binding of SHP-1 to Ros is selective compared to six other receptor tyrosine kinases. The interaction is mediated by the SHP-1 NH(2)-terminal SH2 domain and Ros phosphotyrosine 2267. Overexpression of SHP-1 results in Ros dephosphorylation and effectively downregulates Ros-dependent proliferation and transformation. We propose that SHP-1 is an important downstream regulator of Ros signaling.
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PMID:Negative regulation of Ros receptor tyrosine kinase signaling. An epithelial function of the SH2 domain protein tyrosine phosphatase SHP-1. 1126 49

Plasma membrane-anchored proteases have key roles in cell signaling, migration and refashioning the cell surface and its surroundings. We report the first example of a plasma membrane-anchored protease on mature sperm, testase 1 (ADAM 24). Unlike other studied sperm ADAMs (fertilin alpha and beta, cyritestin) whose metalloprotease domains are removed during sperm development, we found testase 1 retains an active metalloprotease domain, suggesting it acts as a protease on mature sperm. Testase 1 is a glycoprotein (molecular mass 88 kDa), localized to the equatorial region of the plasma membrane of cauda epididymal sperm. Typically, proteolytic removal of the pro-domain is an initial activation step for ADAM proteases. The pro-domain of the testase 1 precursor (108 kDa) is proteolytically removed as sperm transit the caput epididymis to produce processed (mature) testase 1 (88 kDa). Testase 1 is unique among all studied ADAMs in that its proteolytic processing occurs on the sperm plasma membrane instead of at an intracellular site (the Golgi). Using GST-fusion proteins and a synthetic testase 1 C-terminal peptide, we found that the cytoplasmic tail of testase 1 could be phosphorylated in vitro by protein kinase C (PKC). Thus testase 1 apparently has a cytoplasmic PKC phosphorylation site(s). Protein kinase C is known to stimulate other ADAMs' protease activity. Because events of the acrosome reaction include PKC activation, we speculate that testase 1 protease function could be important in sperm penetration of the zona pellucida after sperm PKC is activated during the acrosome reaction.
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PMID:Testase 1 (ADAM 24) a plasma membrane-anchored sperm protease implicated in sperm function during epididymal maturation or fertilization. 1130 8

This study concerned the minimum and optimum effective doses of calcium chloride needed for induction of chemosterilization in male albino rats, 30 days after a single intratesticular injection of calcium chloride (CaCl2.2H2O) solution at 2.5, 5, 10 or 20 mg per 100 g body weight per testis. There was a significant diminution in the relative wet weight of the sex organs (p<0.01), epididymal sperm count (p<0.001), plasma concentration of testosterone (p<0.01), testicular activities of delta5,3beta-hydroxy steroid dehydrogenase (delta5,3beta-HSD), 17beta-hydroxy steroid dehydrogenase (17beta-HSD) (p<0.01), glutathione S-transferase (GST) (p<0.01), superoxide dismutase (SOD) (p<0.01), and peroxidase (p<0.01), significant elevations in testicular content of malondialdehyde (MDA) and conjugated dienes (p<0.01), along with derangement of seminiferous tubular architecture and degeneration of the Leydig cells in the testis and elevations in the concentrations in the plasma of LH and FSH (p<0.01), commencing at a dose of 5 mg, with the greatest effects at a dose of 20 mg. No significant alterations in these factors occurred at the dose of 2.5 mg in comparison to the control that received only the vehicle. There was no significant alteration in the plasma concentrations of prolactin (p>0.05), corticosterone (p>0.05) or fasting blood glucose or in the rectal temperature (p>0.05) at any of the doses relative to the control group, suggesting that this chemosterilizing procedure did not exert any chronic stress on the experimental animals. From these observations, it may be suggested that 5 mg should be considered as the minimum dose, and 10 mg or 20 mg as the optimum dose, whereas 2.5 mg was ineffective for induction of chemosterilization. There would seem to be little point in using more than 20 mg of calcium chloride for this purpose. Intratesticular injection of calcium chloride at an effective dose may be considered as an alternative to surgical castration.
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PMID:Dose-dependent response to an intratesticular injection of calcium chloride for induction of chemosterilization in adult albino rats. 1250 39

Protection of maturing sperm from potential endogenous or exogenous harmful substances during their transit throughout the epididymis is a critical event. The authors studied the activity of gamma-glutamyl transpeptidase (GGT) and glutathione S-transferase (GST), and glutathione (GSH) levels in epithelial cell cultures from human caput, corpus, and cauda epididymides. Tissue was obtained from patients undergoing therapeutic orchidectomy for prostatic cancer. Enzymatic activity was measured in conditioned media and cellular fractions. Androgen influence was also evaluated. Both enzymatic activities were found in cellular homogenates and conditioned media from cultures of all epididymal regions. GGT activity was highest in cultures from cauda epididymis, both in conditioned media and cell fractions, while GST activity did not show regional differences in conditioned media, but exhibited higher activity in cell homogenates from cauda cultures than those obtained from corpus and caput epididymis. GSH level showed no regional difference in cell homogenates and it could not be detected in conditioned media by the method used. Presence of different concentrations of dihydrotestosterone (DHT) had no influence neither on the enzymatic activities nor GSH concentration. The results indicate that GGT and GST are present along the human epididymis and a fraction or isoform of these enzymes might be secreted to the luminal fluid to play a detoxificative role in sperm maturation.
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PMID:Glutathione-related enzymes in cell cultures from different regions of human epididymis. 1262 45

The protein phosphatase PP1gamma2 is critical in the regulation of sperm motility and fertility. Its activity is regulated by its binding proteins and by phosphorylation. We have recently shown that PP1gamma2 is phosphorylated and that the amount of phosphorylated PP1gamma2 increases during sperm epididymal maturation (Huang et al., Biol Reprod 2004; 70:439-447). Microsequencing revealed that protein 14-3-3 coeluted with phosphorylated PP1gamma2 during column chromatography of bovine sperm extracts. Western blot analyses confirmed the presence of protein 14-3-3 not only in bovine spermatozoa but also in spermatozoa of diverse species-bull, hamster, horseshoe crab, monkey, rat, turkey, and Xenopus. The binding between PP1gamma2 and protein 14-3-3 was confirmed by coimmunoprecipitation experiments and in pull-down assays with recombinant GST-14-3-3. Western blot analysis and protein 14-3-3 immunoprecipitates with antibodies against the consensus binding domain of protein 14-3-3 reveal that, in addition to PP1gamma2, at least two other protein 14-3-3 binding partners are present in spermatozoa. Fluorescence immunocytochemistry results indicate that phosphorylated PP1gamma2 and protein 14-3-3 both localize to the postacrosomal region of the head and principal piece of bovine spermatozoa. Together, these results provide conclusive evidence that protein 14-3-3 is present in mature spermatozoa and that PP1gamma2 is one of its binding partners.
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PMID:Protein 14-3-3zeta binds to protein phosphatase PP1gamma2 in bovine epididymal spermatozoa. 1502 37

We have identified for the first time the presence of chloride intracellular channel (CLIC) proteins in bovine epididymal spermatozoa. CLIC1 was discovered during microsequencing of proteins that co-purified with protein phosphatase 1, PP1gamma2, in sperm extracts. In addition to CLIC1, Western blot showed that two additional CLIC family members, CLIC4 and CLIC5, are also present in spermatozoa. CLIC fusion proteins, GST-CLIC1, GST-CLIC4 and GST-CLIC5, were all able to bind to PP1gamma2 in sperm extracts during pull-down assays. Immunofluorescence microscopy revealed that each of the three isoforms occupies a distinct location within the cell. Given that PP1gamma2 is a key enzyme regulating sperm motility, PP1gamma2-binding proteins, such as the CLIC proteins, are likely to play significant roles in sperm function.
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PMID:Identification of chloride intracellular channel proteins in spermatozoa. 1514 83


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