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)

Cadmium is a common environmental and occupational hazard and its adverse effect on reproductive organ has been well documented. The present study is planned to delineate the mechanism of Cd toxicity in rat testes. Our study shows that Cd causes apoptosis in sertoli-germ cells which is governed by oxidative stress. We assayed ROS, GSH and MMP to ensure the role of oxidative stress, further confirmed it by thiol modulators. The initial biochemical response shown in sertoli-germ cells was a significant rise in intracellular calcium followed by a drastic fall in MMP and then ROS generation. The downstream events included cytochrome c release leading to caspase-3 activation and culminating in cell death via apoptosis. Furthermore Cd disrupted the spermatogenic pathway as evident by suppression in tesmin and LDH-X levels.
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PMID:Interplay of early biochemical manifestations by cadmium insult in sertoli-germ coculture: an in vitro study. 2166 5

The widespread use of tributyltin (TBT) as biocides in antifouling paints and agricultural chemicals has led to environmental and marine pollution. Human exposure occurs mainly through TBT contaminated seafood and drinking water. It is a well known endocrine disruptor in mammals, but its molecular mechanism in testicular damage is largely unexplored. This study was therefore, designed to ascertain effects of tributyltin chloride (TBTC) on sertoli-germ cell co-culture in ex-vivo and in the testicular tissue in-vivo conditions. An initial Ca(2+) rise followed by ROS generation and glutathione depletion resulted in oxidative damage and cell death. We observed p38 and JNK phosphorylation, stress proteins (Nrf2, MT and GST) induction and mitochondrial depolarization leading to caspase-3 activation. Prevention of TBTC reduced cell survival and cell death by Ca(2+) inhibitors and free radical scavengers specify definitive role of Ca(2+) and ROS. Sertoli cells were found to be more severely affected which in turn can hamper germ cells functionality. TBTC exposure in-vivo resulted in increased tin content in the testis with enhanced Evans blue leakage into the testicular tissue indicating blood-testis barrier disruption. Tesmin levels were significantly diminished and histopathological studies revealed marked tissue damage. Our data collectively indicates the toxic manifestations of TBTC on the male reproductive system and the mechanisms involved.
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PMID:Tributyltin chloride induced testicular toxicity by JNK and p38 activation, redox imbalance and cell death in sertoli-germ cell co-culture. 2405