Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.62 (caspase-9)
 7,507 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondria constantly undergo fusion and fission that are necessary for the maintenance of organelle fidelity. However, growing evidence has shown that abnormal mitochondrial fusion and fission participate in the regulation of apoptosis. Mitochondrial fusion is able to inhibit apoptosis, whereas mitochondrial fission is involved in the initiation of apoptosis. It remains elusive as to whether mitochondrial fission can regulate DNA fragmentation during apoptosis. Mitochondrial fission is triggered by dynamin-related protein-1 (Drp1), whereas mitofusin 1 (Mfn 1) is able to induce mitochondrial fusion. Here, we report that Drp1 is required for the release of endonuclease G from mitochondria. Knockdown of Drp1 can attenuate DNA fragmentation. Our data further show that Mfn 1 prevents endonuclease G release from mitochondria and the consequent DNA fragmentation. Intriguingly, Mfn 1 could inhibit the activation of caspase-3 and caspase-9, which are necessary for endonuclease G translocation to the nucleus. Our results provide novel evidence that DNA fragmentation is regulated by the mitochondrial fission machinery.
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PMID:Mitochondrial fission controls DNA fragmentation by regulating endonuclease G. 2059 82

Cadmium (Cd) is a toxic metal that is involved in apoptosis. The present study was conducted to investigate the mechanism of Cd-induced apoptosis and the protective effects of vitamin E on rat testes. Thirty-two adult Wistar rats were divided into four groups. The control group was injected with saline and three other groups received Cd, Cd+vitamin E, and vitamin E. Intraperitoneal injection was performed for 28 days. On the 29th day, the rats were slaughtered, their peritoneum was opened, and their left testis removed and weighed. The mRNA expression of apoptosis and mitochondrial dynamics genes were assessed using real-time PCR, and caspase-3/7 activation using the caspase-3/7 Assay. The groups were not significantly different in terms of testicular weight. Compared with the control group, the mRNA expression levels of Bax and caspase-9 genes increased in the rats' testes receiving Cd, the mRNA expression levels of mitofusin 1 (Mfn1) and mitofusin2 (Mfn2) genes decreased, and those of Bcl-2 remained unchanged. Vitamin E was found to significantly decrease the mRNA expression of Bax and caspase-9 genes and increase the mRNA Mfn1, Mfn2, and Bcl-2 in the rats' testes receiving Cd. The ratio of Bax/Bcl-2 and caspase-3/7 activity increased in the Cd-exposed rats compared with the control. Vitamin E remarkably attenuated the Cd-induced effects. According to the obtained results, Cd exerts its apoptotic effects through the mitochondrial pathway by increasing the ratio of Bax/Bcl-2 and activating caspases in the rats' testes, and vitamin E plays a protective role against Cd-induced apoptosis.
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PMID:Protective effects of vitamin E on cadmium-induced apoptosis in rat testes. 3162 Aug 23