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)

Differentiating male germ cells express a testis-specific form of cytochrome c (Cyt c(T)) that is distinct from the cytochrome c expressed in somatic cells (Cyt c(S)). To examine the role of Cyt c(T) in germ cells, we generated mice null for Cyt c(T). Homozygous Cyt c(T)(-/-) pups were statistically underrepresented (21%) but developed normally and were fertile. However, spermatozoa isolated from the cauda epididymis of Cyt c(T)-null animals were less effective in fertilizing oocytes in vitro and contain reduced levels of ATP compared to wild-type sperm. Sperm from Cyt c(T)-null mice contained a greater number of immotile spermatozoa than did samples from control mice, i.e., 53.1% +/- 13.7% versus 33.2% +/- 10.3% (P < 0.0001) for vas deferens sperm and 40.1% +/- 9.6% versus 33.2% +/- 7.5% (P = 0.0104) for epididymal sperm. Cyt c(T)-null mice often exhibit early atrophy of the testes after 4 months of age, losing germ cells as a result of increased apoptosis. However, no difference in the activation of caspase-3, -8, or -9 was detected between the Cyt c(T)(-/-) testes and controls. Our data indicate that the Cyt c(T)-null testes undergo early atrophy equivalent to that which occurs during aging as a consequence of a reduction in oxidative phosphorylation.
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PMID:Testis-specific cytochrome c-null mice produce functional sperm but undergo early testicular atrophy. 1210 Dec 47

Gene expression was measured during t10c12-CLA-induced body fat reduction in a polygenic obese line of mice. Adult mice (n = 185) were allotted to a 2 x 2 factorial experiment consisting of either nonobese (ICR-control) or obese (M16-selected) mice fed a 7% fat, purified diet containing either 1% linoleic acid (LA) or 1% t10c12-CLA. Body weight (BW) by day 14 was 12% lower in CLA- compared with LA-fed mice (P < 0.0001). By day 14, t10c12-CLA reduced weights of epididymal, mesenteric, and brown adipose tissues, as a percentage of BW, in both lines by 30, 27, and 58%, respectively, and increased liver weight/BW by 34% (P < 0.0001). Total RNA was isolated and pooled (4 pools per tissue per day) from epididymal adipose (days 5 and 14) of the obese mice to analyze gene expression profiles using Agilent mouse oligo microarray slides representing > 20,000 genes. Numbers of genes differentially expressed by greater than or equal to twofold in epididymal adipose (days 5 and 14) were 29 and 125, respectively. It was concluded that, in adipose tissue, CLA increased expression of uncoupling proteins (1 and 2), carnitine palmitoyltransferase system, tumor necrosis factor-alpha (P < 0.05), and caspase-3 but decreased expression of peroxisome proliferator-activated receptor-gamma, glucose transporter-4, perilipin, caveolin-1, adiponectin, resistin, and Bcl-2 (P < 0.01). In conclusion, this experiment has revealed candidate genes that will be useful in elucidating mechanisms of adipose delipidation.
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PMID:Functional genomic characterization of delipidation elicited by trans-10, cis-12-conjugated linoleic acid (t10c12-CLA) in a polygenic obese line of mice. 1588 70

The effect of exercise training on tumor necrosis factor-alpha (TNF-alpha) signaling was investigated in rat epididymal adipocytes. Incubation of isolated adipocytes with TNF-alpha (20 ng/ml) for 5 h enhanced the expression of the inhibitor apoptosis protein 2 (IAP2) gene without any enhancement of caspase-3 activity in both the sedentary control (C) and exercise-trained (TR) groups. However, the ability of TNF-alpha to enhance IAP2 gene expression was significantly greater in TR than in C rats. The basal expression of the IkappaB kinase beta (IKK beta) gene and that of the BCL-x(L) gene were also higher in TR than in C rats. Mn-superoxidedismutase contents in adipocytes were higher in TR than in C rats. Moreover, no apoptotic nucleuses of adipocytes in response to acute exercise were observed in either group at least up to 5 h after exercise. Exercise training also enhanced the inhibitory effect of TNF-alpha on the gene expression of the fatty acid synthase (FAS), a lipogenic enzyme, suggesting that fatty acid synthesis may be reduced. Thus, exercise training enhanced TNF-alpha signaling directed toward the expressions of survival signals and the suppression of FAS gene expression.
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PMID:Exercise training enhances tumor necrosis factor-alpha-induced expressions of anti-apoptotic genes without alterations in caspase-3 activity in rat epididymal adipocytes. 1612 69

B-cell lymphoma 2 (BCL2) family kin (BFK) is a recently identified novel protein that is similar to proteins of the BCL2 family. In the present study, we discovered that the mouse Bfk transcript is expressed at the highest level in the epididymis. Two transcripts of 0.9 and 2.6 kb in size were identified, with alternative exon 4 structures, resulting in a difference in the last three to five amino acids of the variants. However, the 0.9-kb transcript was found to be the predominant form in the epididymis and mammary gland, another tissue with strong Bfk expression. Epididymal Bfk expression was regulated both by androgens and other testicular factors. It is thus one of the few initial-segment enriched genes under androgen control, the majority of them being regulated by other testicular factors. BFK protein was expressed specifically in the principal cells of the epididymis. Its nuclear localization was evident in the initial segment and caput epididymis and in the epithelium of pregnant female mammary gland. The expression of BFK-enhanced green fluorescent protein recombinant protein in epididymal cells further confirmed the predominant nuclear localization of BFK with nucleo-cytoplasmic shuttling. Overexpressing BFK in epididymal cells did not induce apoptosis. However, enhanced caspase 3 activation was observed in the presence of BFK upon staurosporine-induced apoptosis. This suggests that BFK may have a proapoptotic role only after the process has been initiated by other mechanisms. Being exceptionally highly expressed in the initial segment, Bfk is suggested to have a role in the differentiation of this segment of the epididymis.
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PMID:Bfk, a novel member of the bcl2 gene family, is highly expressed in principal cells of the mouse epididymis and demonstrates a predominant nuclear localization. 1741 10

Toxicity of the polychlorinated biphenyls (PCBs) depends on their molecular structure. Mechanisms by prenatal exposure to a non-dioxin-like PCB, 2,2',3,4',5',6-hexachlorobiphenyl (PCB 132) that may act on reproductive pathways in male offspring are relatively unknown. The purpose was to determine whether epididymal sperm function and expression of apoptosis-related genes were induced or inhibited by prenatal exposure to PCB 132. Pregnant rats were treated with a single dose of PCB 132 at 1 or 10 mg/kg on gestational day 15. Male offspring were killed and the epididymal sperm counts, motility, velocity, reactive oxygen species (ROS) generation, sperm-oocyte penetration rate (SOPR), testicular histopathology, apoptosis-related gene expression and caspase activation were assessed on postnatal day 84. Prenatal exposure to PCB 132 with a single dose of 1 or 10 mg/kg decreased cauda epididymal weight, epididymal sperm count and motile epididymal sperm count in adult offspring. The spermatozoa of PCB 132-exposed offspring produced significantly higher levels of ROS than the controls; ROS induction and SOPR reduction were dose-related. In the low-dose PCB 132 group, p53 was significantly induced and caspase-3 was inhibited. In the high-dose group, activation of caspase-3 and -9 was significantly increased, while the expressions of Fas, Bax, bcl-2, and p53 genes were significantly decreased. Gene expression and caspase activation data may provide insight into the mechanisms by which exposure to low-dose or high-dose PCB 132 affects reproduction in male offspring in rats. Because the doses of PCB 132 administered to the dams were approximately 625-fold in low-dose group and 6250-fold higher in high-dose group than the concentration in human tissue levels, the concentrations are not biologically or environmentally relevant. Further studies using environmentally relevant doses are needed for hazard identification.
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PMID:Exposure in utero to 2,2',3,3',4,6'-hexachlorobiphenyl (PCB 132) impairs sperm function and alters testicular apoptosis-related gene expression in rat offspring. 1744 52

2-Bromopropane (2-BP) was used as an alternative for ozone-depleting solvents, which caused reproductive disorders in male workers and laboratory animals. A recent study indicated that 2-BP impaired antioxidant cellular defences and enhanced lipid peroxidation (LPO). Melatonin is a powerful endogenous antioxidant. We hypothesized that reactive oxygen species (ROS) and lipid peroxidation are involved in 2-BP-induced testicular toxicities. To test the hypothesis, we investigated the effects of melatonin on 2-BP-induced testicular toxicities. Rats were intraperitoneally injected with 2-BP (1g/kg) with or without melatonin (5mg/kg), then sacrificed on 7th day after 2-BP injection. Epididymal and testicular tissues were examined for biochemical and histopathological changes. Apoptotic cells in testis were detected by TUNEL staining and immunohistochemistry for active caspase-3. Exposure to 2-BP significantly decreased epididymal sperm count and morphological normal sperms. 2-BP also induced vacuolation and atrophy of the seminiferous tubules, reduction of spermatogonia and apoptosis of germ cells. 2-BP significantly increased TBARS levels in plasma and epididymis, and decreased GSH content in testis and epididymis. Pretreatment with melatonin counteracted 2-BP-induced oxidative stress, ameliorated apoptosis in testis and attenuated histopathological damage in testis. In addition, pretreatment with melatonin significantly attenuated 2-BP-induced sperm morphological changes. We conclude that pretreatment with melatonin attenuates 2-BP-induced testicular toxicity through its ROS scavenging and anti-apoptotic effects.
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PMID:Melatonin pretreatment attenuates 2-bromopropane-induced testicular toxicity in rats. 1906 34

Lead is a ubiquitous environmental and industrial pollutant that may have toxic effects on the male. Vitamins may protect against toxic effects of lead in the liver and reproductive system, which is confirmed by our initial research. The aim of this study was to further investigate the protective effects of vitamins (ascorbic acid combined with thiamine) on lead acetate (Pb)-induced reproductive toxicities in mice and study the possible mechanisms underlying these effects. Forty-five male mice were randomly divided into 3 groups, 15 mice in each and received daily intragastric administration with control, Pb (20 mg/kg), and Pb+vitamins (ascorbic acid of 420 mg/kg+thiamine of 30 mg/kg) for 6 weeks, respectively. The Pb-treated animals showed significant decreases in the epididymal sperm count and motility compared to the control group, while the Pb+vitamins group had significant increases for these variables. Moreover, an increasing apoptosis of germinal cells induced by Pb was reduced by vitamin treatment. Pb induced the activation of Caspase-3, Fas/Fas-L and Bcl-2 with elevated levels, and the adaptor protein primarily regulated signaling through Fas and required for Fas-induced apoptosis. In conclusion, ascorbic acid combined with thiamine exhibited protective effect on reproductive system by inhibiting Pb-induced excessive cell apoptosis.
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PMID:The protective effect of ascorbic acid and thiamine supplementation against damage caused by lead in the testes of mice. 1922 66

Treatment of p53(-/-) mice orally with caffeine, voluntary exercise or their combination for 2 weeks prior to a single irradiation with UVB (i) decreased the weight of the epididymal fat pads by 22, 40 and 56%, (ii) decreased the thickness of the dermal fat layer by 10, 26 and 42%, (iii) increased the number of apoptotic sunburn cells by 29, 100 and 489%, (iv) increased the number of caspase-3-positive cells by 33, 117 and 667% and (v) increased the number of mitotic cells with cyclin B1-positive staining by 40, 210 and 510%, respectively. Pearson's correlation coefficient indicated a statistically significant inverse relationship between the level of tissue fat and the number of mitotic cells with cyclin B1 in p53(-/-) mice but not in p53(+/+) littermates. Western blot analysis indicated that treatment of p53(-/-) mice with caffeine together with exercise increased the level of cyclin B1 significantly more than in p53(+/+) mice. p53(-/-) mice, but not p53(+/+) mice, treated with caffeine during exercise exhibited a dramatic decrease in the level of survivin. Our results suggest that voluntary exercise in combination with oral caffeine may exert a synergistic increase in UVB-induced apoptosis and that tissue fat may be a more important modulator of apoptosis and carcinogenesis in p53-deficient mice than in p53-normal mice. The stimulatory effects on apoptosis in p53(-/-) mice by the combination treatment might be associated with increased levels of cyclin B1 and decreased levels of survivin.
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PMID:Oral administration of caffeine during voluntary exercise markedly decreases tissue fat and stimulates apoptosis and cyclin B1 in UVB-treated skin of hairless p53-knockout mice. 1992 39

In the adult rat, the superior spermatic nerve (SSN) and inferior spermatic nerve (ISN) are involved in regulating testosterone secretion and spermatogenesis, in addition to endocrine control mechanisms. However, there are currently few data on how the testis nerve supply regulates testicular development and related mechanisms. The present study was thus designed to investigate the regulating effects of testis nerve supply to testicular maturation, spermatogenesis and the involved mechanisms from prepuberty to adulthood in rats. We transected the SSNs and ISNs of rats on postnatal day (PD) 30 and then analyzed changes in testicular morphology and cauda epididymal sperm content, cell proliferation and apoptosis and primary spermatocyte meiosis on PD60 and PD90. The results demonstrated that testicular denervation significantly reduced testis mass, cauda epididymal sperm counts and serum testosterone concentrations. Proliferating cell nuclear antigen (PCNA) and cleaved caspase-3 immunohistochemistry staining proved that the denervation had no influence on the proliferation of spermatogonia and primary spermatocytes, but obviously promoted the apoptosis of round spermatids and Leydig cells. It is novel that denervation reduced the meiotic activation of zygotene and pachytene spermatocytes through the expression of synaptonemal complex protein 3 (SCP3)-a marker of meiosis. In addition, RT-PCR showed that testis denervation significantly decreased testis 3beta-hydroxysteroid dehydrogenase 1 (3beta-HSD1) and luteinizing hormone receptor (LHR) mRNA levels, but had no obvious influence on testis follicle stimulating hormone receptor (FSHR) mRNA expression. These results suggest that the testicular nerve supply plays an important role in supporting seminiferous tubule development and spermatogenesis from prepuberty to adulthood.
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PMID:Testicular denervation in prepuberty rat inhibits seminiferous tubule development and spermatogenesis. 2042 80

The aim of this study was to investigate the different testicular toxicity and the role of apoptosis in the possible mechanism induced by the two isomers of bromopropanes (BPs) in the same dosage. Following the 14-day treatment with a single dose of 1-BP and 2-BP (1 g/kg), male rats were killed and a series of experiments were performed. 1-BP and 2-BP both significantly decreased the epididymal sperm count, while only 2-BP induced an increase in sperms with abnormal heads. Morphological evaluation showed that 1-BP did not cause morphological changes in seminiferous epithelium, but 2-BP treatment resulted in the disappearance of spermatogonia, atrophy of the seminiferous tubules and degeneration of germ cells. 2-BP significantly increased the TUNEL-positive cells and the activation of caspase-3 and decreased the genes and proteins expression of Bax, Bcl-2 and p53. In contrast, there were no significant changes in the expression of apoptosis-related genes and proteins in 1-BP group, though the TUNEL-positive cells were significantly increased. Taken together, this study indicated that those two isomers both have toxicity in male rats, however, the testicular toxicity and the role of apoptosis in the toxic mechanism induced by 1-BP and 2-BP may be different.
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PMID:Apoptosis contributes to testicular toxicity induced by two isomers of bromopropanes. 2055 30


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