Cyclic-AMP Inhibits Nitric Oxide-Induced Apoptosis in Human Osteoblast: The Regulation of Caspase-3, -6, -9 and the Release of Cytochrome c in Nitric Oxide-Induced Apoptosis by cAMP.
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- CHAE Han-Jung
- Department of Dental Pharmacology and Wonkwang Dental Research Institute, School of Dentistry, Wonkwang University Department of Pharmacology and Institute of Cardiovascular Research, School of Medicine, Chonbuk National University
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- CHAE Soo-Wan
- Department of Pharmacology and Institute of Cardiovascular Research, School of Medicine, Chonbuk National University
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- AN Nyeon-Hyoung
- College of Pharmacy, and School of Oriental Medicine, Wonkwang University
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- KIM Jong-Hwan
- Department of Gynecology, and School of Oriental Medicine, Wonkwang University
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- KIM Chul-Won
- Department of Gynecology, and School of Oriental Medicine, Wonkwang University
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- YOO Sim-Keun
- Department of Gynecology, and School of Oriental Medicine, Wonkwang University
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- KIM Hong-Hee
- National Research Laboratory for Bone Metabolism and Research Center for Proteinous Materials, Chosun University
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- LEE Zang-Hee
- National Research Laboratory for Bone Metabolism and Research Center for Proteinous Materials, Chosun University
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- KIM Hyung-Ryong
- Department of Dental Pharmacology and Wonkwang Dental Research Institute, School of Dentistry, Wonkwang University
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Abstract
Nitric oxide (NO) induces apoptotic cell death and cAMP has a significantly protective effect on NO-induced cytotoxicity in human osteoblasts, MG-63 cells. Treatment with S-nitroso-N-acetylpenicillamine (SNAP)(0.6 mM) resulted in genomic DNA fragmentation, characteristic of apoptosis. However, concomitant incubation of the cells with either DBcAMP or forskolin markedly inhibited SNAP-induced apoptosis in a dose-dependent manner. Furthermore, pretreatment of MG-63 cells with H-89 or KT5720, which is known to inhibit cAMP-dependent protein kinase (PKA), abolished the protective effect of DBcAMP and forskolin on SNAP-induced apoptosis. In this study, we explored the involvement of caspases in the regulatory mechanism of SNAP-induced apoptosis by cAMP. Our data show that DBcAMP or forskolin blocked SNAP-induced caspase-3-like cysteine protease activation and that H-89, a PKA inhibitor, reversed the cAMP-induced regulatory effect of caspase-3 like protease. Consistent with the results, cAMP inhibited the proteolytic cleavage of caspase-3, -6, -9 and cytochrome c release to cytoplasm. The inhibition of caspase-3 activation did not block SNAP-induced cytochrome c release to cytoplasm, suggesting that caspase-3 activation may occur downstream of cytochrome c release. In summary, these findings show that the exposure of MG-63 cells to cAMP analogs renders them more resistant to NO-induced damage and suggests the presence of regulatory mechanisms of the cell death pathway by cAMP in which caspase-3, -6, and -9 and cytochrome c release serves to mediate NO-induced apoptosis.
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 24 (5), 453-460, 2001
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390001204626609664
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- NII Article ID
- 110003638491
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- NII Book ID
- AA10885497
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- COI
- 1:CAS:528:DC%2BD3MXjt1alsb8%3D
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 5763814
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- PubMed
- 11379759
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed