Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antisperm antibodies (ASA) are the main cause of immunological infertility, as they impair sperm function by binding to the sperm membrane. In this study, we isolated highly enriched sperm membrane proteins by two-dimensional (2D) gel electrophoresis. Isoelectric focusing, as a first dimension, was performed on precast DryStrip IPG 4-7. The second dimension was carried out on 12% sodium dodecyl sulphate-polyacrylamide gels. A total of 18 antigens were identified by the subsequent 2D Western blotting using ASA from seminal plasma samples of infertile patients. Six of the recognized proteins were isolated and analysed by means of mass spectrometry and peptide matching. They were identified as heat shock proteins HSP70 and HSP70-2, the disulphide isomerase ER60, the inactive form of caspase-3 and two subunits of the proteasome (component 2 and zeta chain). The biochemical identification of these proteins will be helpful in understanding the mechanisms by which ASA impair both sperm function and fertilization. Thus, these proteins may also be useful in the development of reliable methods for ASA detection.
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PMID:Isolation and identification of sperm membrane antigens recognized by antisperm antibodies, and their possible role in immunological infertility disease. 1116 Aug 36

The Fas system is involved in the regulation of germ cell apoptosis associated with testicular injury in experimental animals exposed to various insults. We tested the hypothesis that enhanced germ cell apoptosis mediated by the up-regulation of the Fas system and the activation of caspases may be involved in ethanol-induced testicular injury. Adult Wistar rats were fed either ethanol in Lieber-DeCarli liquid diet or an isocaloric control diet for 12 weeks. Marked Sertoli cell vacuolization and germ cell degeneration were observed in the testes of ethanol-treated rats (ETR) by both light and electron microscopy. Enhanced apoptosis of germ cells in ETR was detected by the terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick end labelling (TUNEL) method, transmission electron microscopy, and was associated with elevated activity of caspase-3, -8 and -9. The expression levels of the Fas ligand (FasL) in Sertoli cells and of both Fas and caspase-3 in germ cells of ETR detected immunohistochemically were higher than those of the control testes. Furthermore, reverse transcriptase-polymerase chain reaction analysis demonstrated an increase in both Fas and FasL mRNA levels in ETR. Fas system up-regulation and the elevated activity of caspases in the testes of ETR may be a reflection of ethanol-induced testicular injury resulting in enhanced germ cells apoptosis, which may be involved in infertility associated with alcohol abuse.
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PMID:Involvement of Fas system and active caspases in apoptotic signalling in testicular germ cells of ethanol-treated rats. 1203 Oct 44

Apoptosis is necessary for the development and maturation of Leydig cells. However, increased apoptosis results the decline of testosterone production, which may increase germ cell apoptosis and the possibility of infertility. There are several aspects contributing to Leydig cell apoptosis such as ethane dimethanesulphonate (EDS), glucocorticoid, developmental stage and some hormones including FSH, LH/hCG and testosterone. A number of genes are involved in the regulation of Leydig cells apoptosis. It was reported that SCF/c-kit, Bcl-2 and Bcl-xl inhibited the apoptosis while caspase-3, Fas, Bax and clusterine stimulated it.
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PMID:[Leydig cell apoptosis and its regulation]. 1286 41

The physiological apoptosis that occurs in immature testis appears to be necessary for the maturation of this tissue. Thus, inhibition of the early apoptotic wave associated with the first round of spermatogenesis is followed by accumulation of spermatogonia and infertility later in life. To identify the cell types undergoing apoptosis in immature rat testis and to characterize the relationship between this apoptosis and progression of the first wave of spermatogenesis, sequential viable segments of seminiferous tubules from 8-, 18-, and 26-day-old rats were examined under a phase-contrast microscope. One novel observation was the existence of pronounced stage-specificity during the peak of apoptosis at the very early postnatal ages of 18 and 26 days. Increased apoptosis of pachytene spermatocytes in stages VII-VIII was the major feature that distinguished immature spermatogenesis from the corresponding adult process. The frequency of apoptosis among type A spermatogonia in immature stages IX-I was also elevated in comparison to the corresponding mature stages. The age-related peak of apoptosis was mediated by caspase 3; furthermore, stage-dependent expression of Bax in midpachytene spermatocytes was observed in the 18- and 26-day-old testis. These observations suggest that this Bax-regulated, caspase 3-mediated, increased apoptosis of midpachytene spermatocytes during the first wave of immature spermatogenesis represents a major difference in comparison to apoptosis occurring in the mature testis, and it may play an important regulatory role in establishing spermatogenesis in the rat testis.
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PMID:Increased apoptosis occurring during the first wave of spermatogenesis is stage-specific and primarily affects midpachytene spermatocytes in the rat testis. 1452 36

Apoptosis is characterized by a variety of changes resulting in the recognition and phagocytosis of apoptotic cells. Caspases (cysteinyl aspartate-specific proteinases) play a central role in the regulation of apoptosis in the human seminiferous epithelium. They are expressed as inactive proenzymes and participate in a cascade triggered in response to pro-apoptotic signals. To date, 14 caspases have been implicated in the human apoptotic pathway cascade. Among these, caspase-3 is considered to be a major executioner protease. Since apoptosis is a universal suicide system in almost all cells, a close control via molecular, endocrine and physical factors establishes homeostasis of cell growth and death. The proper regulation of the caspase cascade plays an important role in sperm differentiation and testicular maturity. However, caspases have been implicated in the pathogenesis of multiple andrological pathologies such as impaired spermatogenesis, decreased sperm motility and increased levels of sperm DNA fragmentation, testicular torsion, varicocele and immunological infertility. Future research may provide a better understanding of the regulation of caspases, which may help us to manipulate the apoptotic machinery for therapeutic benefits. In this review, we summarize the consequences of caspase activation, aiming to clarify their role in the pathogenesis of male infertility.
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PMID:Role of caspases in male infertility. 1500 63

Tritrichomonas foetus is a serious veterinary pathogen, causing bovine trichomoniasis, a sexually transmitted disease leading to infertility and abortion. T. foetus infects the mucosal surfaces of the reproductive tract. Infection with T. foetus leads to apoptotic cell death of bovine vaginal epithelial cells (BVECs) in culture. An affinity-purified cysteine protease (CP) fraction yielding on sodium dodecyl sulfate-polyacrylamide gel electrophoresis a single band with an apparent molecular mass of 30 kDa (CP30) also induces BVEC apoptosis. Treatment of CP30 with the protease inhibitors TLCK (Nalpha-p-tosyl-l-lysine chloromethyl ketone) and E-64 [l-trans-epoxysuccinyl-leucylamide-(4-guanido)-butane] greatly reduces induction of BVEC apoptosis. Matrix-assisted laser desorption ionization-time-of-flight MALDI-TOF mass spectrometry analysis of CP30 reveals a single peak with a molecular mass of 23.7 kDa. Mass spectral peptide sequence analysis of proteolytically digested CP30 reveals homologies to a previously reported cDNA clone, CP8 (D. J. Mallinson, J. Livingstone, K. M. Appleton, S. J. Lees, G. H. Coombs, and M. J. North, Microbiology 141:3077-3085, 1995). Induction of apoptosis is highly species specific, since the related human parasite Trichomonas vaginalis and associated purified CPs did not induce BVEC death. Fluorescence microscopy along with the Cell Death Detection ELISA(PLUS) assay and flow cytometry analyses were used to detect apoptotic nuclear condensation, DNA fragmentation, and changes in plasma membrane asymmetry in host cells undergoing apoptosis in response to T. foetus infection or incubation with CP30. Additionally, the activation of caspase-3 and inhibition of cell death by caspase inhibitors indicates that caspases are involved in BVEC apoptosis. These results imply that apoptosis is involved in the pathogenesis of T. foetus infection in vivo, which may have important implications for therapeutic interference with host cell death that could alter the course of the pathology in vivo.
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PMID:Tritrichomonas foetus induces apoptotic cell death in bovine vaginal epithelial cells. 1521 60

Ubiquitination is required throughout all developmental stages of mammalian spermatogenesis. Ubiquitin C-terminal hydrolase (UCH) L1 is thought to associate with monoubiquitin to control ubiquitin levels. Previously, we found that UCHL1-deficient testes of gad mice have reduced ubiquitin levels and are resistant to cryptorchid stress-related injury. Here, we analyzed the function of UCHL1 during the first round of spermatogenesis and during sperm maturation, both of which are known to require ubiquitin-mediated proteolysis. Testicular germ cells in the immature testes of gad mice were resistant to the early apoptotic wave that occurs during the first round of spermatogenesis. TUNEL staining and cell quantitation demonstrated decreased germ cell apoptosis and increased numbers of premeiotic germ cells in gad mice between Postnatal Days 7 and 14. Expression of the apoptotic proteins TRP53, Bax, and caspase-3 was also significantly lower in the immature testes of gad mice. In adult gad mice, cauda epididymidis weight, sperm number in the epididymis, and sperm motility were reduced. Moreover, the number of defective spermatozoa was significantly increased; however, complete infertility was not detected. These data indicate that UCHL1 is required for normal spermatogenesis and sperm quality control and demonstrate the importance of UCHL1-dependent apoptosis in spermatogonial cell and sperm maturation.
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PMID:Ubiquitin C-terminal hydrolase L-1 is essential for the early apoptotic wave of germinal cells and for sperm quality control during spermatogenesis. 1574 22

Cellular stress to ejaculated spermatozoa such as cryopreservation is known to induce caspase-derived, apoptotic signaling. Therefore, the proenzymes and active forms of caspases 1, 3, 8 and 9 were examined by western blot technique in unfrozen and frozen human spermatozoa of infertility patients and of healthy donors. Twenty-two semen samples derived from healthy donors and 26 semen samples of unselected infertility patients were divided into 3 parts, two of them were cryostored at -196 degrees C with 7% or 14% (v/v, final concentration) of glycerol. The caspases were detected by immunoblots with polyclonal rabbit-anti-caspases-antibodies after 15% sodium dodecyl sulfate-polyacrylgel electrophoresis (SDS-PAGE) under reducing conditions. For evaluation of the differences between amounts of caspase protein the luminol/H(2)O(2) method was applied. A significant increase of activated caspase-1 in donors, of caspase-8 in patients and caspase-9 in patients and donors after cryopreservation were found, whereas, the application of 14% glycerol resulted in higher amounts of activated caspase than did 7% glycerol. Possibly, glycerol may also contribute to activation of caspases via direct toxic effects to mitochondria during cryopreservation of spermatozoa. This finding strongly supports an hypothesis of a higher mitochondria-derived apoptosis-sensitivity of spermatozoa in patients than in healthy donors during cryopreservation. Inactive caspase-3 was reduced subsequent to cryopreservation in patients (p<0.05) and non-significant in donors (p<0.05). Active caspase-3 was detectable in all samples but without significant differences between the three assays. It is concluded that mechanisms associated with apoptotic processes deserve attention in cryopreservation of spermatozoa in order to conserve vital sperm functions after thawing.
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PMID:Activation of caspases in human spermatozoa during cryopreservation--an immunoblot study. 1673 10

Echinococcus granulosus is a parasitic cestode causing hydatidosis in intermediate hosts (human and herbivorous). Most symptoms of the disease occur by the pressure exerted on viscera by cysts that are formed upon ingestion of the parasite eggs excreted by definitive hosts (canines). Protoscoleces, the developmental form of the parasite infective to definitive hosts, are formed in the germinal nucleated layer of fertile hydatid cysts. For unknown reasons, some cysts are unable to produce protoscoleces (infertile hydatid cysts). In this study, analysis of DNA fragmentation using TUNEL and agarose gel electrophoresis showed higher levels of apoptosis in infertile cysts as compared to fertile cysts. Additionally, caspase 3 was detected both in fertile and infertile cysts; the activity of this enzyme was found to be higher in infertile cysts. We conclude that apoptosis may be involved in hydatid cyst infertility. This is the first report on the presence of programmed cell death in E. granulosus.
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PMID:Apoptosis as a possible mechanism of infertility in Echinococcus granulosus hydatid cysts. 1703 52

Hydroxysteroid (17beta) dehydrogenase 2 (HSD17B2) has been shown to inactivate both estrogens and androgens and activate 20alpha-hydroxyprogesterone to progesterone. In the present study, we generated transgenic (TG) mice ubiquitously expressing human HSD17B2. The TG mice produced showed growth retardation and delayed eye opening at the postnatal age. Disrupted spermatogenesis was evident in the presence of normal serum and intratesticular testosterone, progesterone, and normal circulating LH concentrations. A proper androgen action in the target tissues was confirmed by normal histological appearance of the prostate and epididymis. Furthermore, quantitative RT-PCR analysis indicated only a slight decrease in androgen-dependent gene expression in the prostate. The disrupted spermatogenesis was not associated with increased germ cell apoptosis as analyzed by caspase-3 activation. However, it resulted in infertility in the HSD17B2 TG males after the age of 3 months, and at the age of 6 months the seminiferous tubules showed a Sertoli cell-only phenotype. The data indicate that the growth retardation and disrupted spermatogenesis are not due to a lack of proper estrogen or androgen action. Interestingly, the testicular phenotype and some of the other phenotypic changes described are typically observed in mice with reduced action of retinoic acid signaling. This, together with the rescue of the testis phenotype by a synthetic retinoic acid receptor agonist (4-[(E)-2-(5, 6, 7, 8-tetrahydro-5, 5, 8, 8-tetramethyl-2-naphthalenyl)-1-propenyl] benzoic acid), suggests a role for HSD17B2 in the action of retinoids, in addition to its oxidative HSD17B activity on sex steroids.
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PMID:Transgenic male mice expressing human hydroxysteroid dehydrogenase 2 indicate a role for the enzyme independent of its action on sex steroids. 1751 Feb 38


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