| Melatonin suppresses NO-induced apoptosis via induction of Bcl-2 expression in PGT-beta immortalized pineal cells. | |
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MedLine Citation:
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PMID: 12220328 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In the present study, we investigated whether melatonin would prevent nitric oxide (NO)-induced apoptotic death of PGT-beta immortalized pineal cells. To examine the protective effect of melatonin, cytotoxicity assay, DNA fragmentation analysis, caspase-3 activity assay, and Western blotting for caspase-3 and poly(ADP-ribose) polymerase (PARP) were performed. Treatment of cells with S-nitroso-N-acetylpenicillamine (SNAP), an NO donor, was shown to induce apoptotic cell death in a dose-dependent manner, and pretreatment with melatonin (0.1 mm) attenuated the occurrence of NO-induced apoptotic cell death. DNA fragmentation in response to NO was also arrested by melatonin. Caspase-3 activity induced by NO was decreased with melatonin treatment. Furthermore, the active fragments of caspase-3 and PARP were almost completely absent following exposure to melatonin. To elucidate the protective mechanisms of action of melatonin, Western blot analyses for Bcl-2 expression and cytochrome c release were carried out. Pretreatment with melatonin (0.1 mm) induced the expression of Bcl-2 and suppressed the release of cytochrome c into the cytosol, thereby arresting NO-induced apoptotic cell death. These results suggest that the antiapoptotic effect of melatonin is associated with induction of Bcl-2 expression in PGT-beta cells, which in turn blocks caspase-3 activation and inhibits cytochrome c release into the cytosol. |
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Authors:
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Yeong-Min Yoo; Sung-Vin Yim; Sung-Soo Kim; Hyun Yong Jang; Ho Zoo Lea; Geun-Cheal Hwang; Jong-Woo Kim; Soon-Ae Kim; Hee Jae Lee; Chang-Ju Kim; Joo-Ho Chung; Kang-Hyun Leem |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of pineal research Volume: 33 ISSN: 0742-3098 ISO Abbreviation: J. Pineal Res. Publication Date: 2002 Oct |
Date Detail:
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Created Date: 2002-09-10 Completed Date: 2003-03-17 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8504412 Medline TA: J Pineal Res Country: Denmark |
Other Details:
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Languages: eng Pagination: 146-50 Citation Subset: IM |
Affiliation:
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Department of Biology, College of Natural Science, Kangwon National University, Chunchon, South Korea. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects* Caspase 3 Caspases / metabolism Cell Line Cytochrome c Group / metabolism DNA Fragmentation / drug effects Melatonin / pharmacology* Mice Nitric Oxide Donors / pharmacology* Pineal Gland / cytology*, drug effects*, metabolism Poly(ADP-ribose) Polymerases / metabolism Proto-Oncogene Proteins c-bcl-2 / biosynthesis* S-Nitroso-N-Acetylpenicillamine / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Cytochrome c Group; 0/Nitric Oxide Donors; 0/Proto-Oncogene Proteins c-bcl-2; 73-31-4/Melatonin; 79032-48-7/S-Nitroso-N-Acetylpenicillamine; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
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