Cyclic-AMP Inhibits Nitric Oxide-Induced Apoptosis in Human Osteoblast : The Regulation of Capase-3, -6, -9 and the Release of Cytochrome c in Nitric Oxide-Induced Apoptosis by cAMP

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概要

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• 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)(0.6mM) 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.

• 社団法人日本薬学会の論文
• 2001-05-01

著者

• Jeong Hyun-ja

  Dep. Of Anatomy School Of Medicine Chonbuk National Univ.

• Na Ho-jeong

  韓国

• AN Nyeon-Hyoung

  College of Pharmacy, Wonkwang University

• Kim Hyung-min

  韓国

• CHAE HAN-JUNG

  Department of Dental Pharmacology, School of Dentistry, Wonkwang University

• CHAE SOO-WAN

  Department of Pharmacology and Institute of Cardiovascular Research, School of Medicine, Chonbuk Nat

• KIM HYUNG-RYONG

  Department of Dental Pharmacology, School of Dentistry, Wonkwang University

• Chae Han-jung

  Dep. Of Pharmacology And Inst. Of Cardiovascular Res. School Of Medicine Chonbuk National Univ.

• Chae Han-jung

  Department Of Dental Pharmacology And Wonkwang Dental Research Institute School Of Dentistry Wonkwan

• KIM Jong-Hwan

  Department of Gynecology, School of Oriental Medicine, Wonkwang University

• KIM Chul-Won

  Department of Gynecology, School of Oriental Medicine, Wonkwang University

• YOO Sim-Keun

  Department of Gynecology, School of Oriental Medicine, Wonkwang University

• KIM Hong-Hee

  National Research Laboratory for Bone Metabolism and Research Center for Proteinous Materials, Chosu

• LEE Zang-Hee

  National Research Laboratory for Bone Metabolism and Research Center for Proteinous Materials, Chosu

• Jung H‐s

  Division In Anatomy And Developmental Biology Department Of Oral Biology College Of Dentistry Yonsei

• Yoo Sim-keun

  Department Of Gynecology School Of Oriental Medicine Wonkwang University

• Kim Chul-won

  Department Of Gynecology School Of Oriental Medicine Wonkwang University

• Kim Hong-hee

  National Research Laboratory For Bone Metabolism

• Lee Zang-hee

  National Research Laboratory For Bone Metabolism And Research Center For Proteinous Materials Chosun

• Jung K

  Laboratory Of Immunomodulator Korea Research Institute Of Bioscience And Biotechnology

• Kim H‐m

  Kyung Hee Univ. Seoul Kor

• Kim Hyung

  College Of Oriental Medicine Kyung Hee University

• Chae Soo-wan

  Dep. Of Pharmacology And Inst. Of Cardiovascular Res. School Of Medicine Chonbuk National Univ.

• Chae Soo-wan

  Department Of Pharmacology And Institute Of Cardiovascular Research School Of Medicine Chonbuk Natio

• Kim Jong-hwan

  Robot Intelligence Technology Laboratory Department Of Electrical Engineering And Computer Science K

• Jung Hyuk-sang

  Department Of Anatomy College Of Oriental Medicine Kyung Hee University

• Kim J‐h

  Korea Res. Inst. Of Bioscience And Biotechnology Daejeon Kor

• Na Ho‐jeong

  College Of Pharmacy Wonkwang University

• Kim Hyung‐min

  Dep. Of Anatomy School Of Medicine Chonbuk National Univ.

• Kim H.

  韓国

• Kim H‐m

  Yonsei Univ. School Of Medicine

• Kang Jang-sook

  Department Of Dental Pharmacology School Of Dentistry Wonkwang University

• Kang Jang-sook

  Department Of Dental Pharmacology School Of Dentistry Wonkwan University

• Jung H‐a

  Coll. Of Oriental Medicine And Inst. Of Oriental Medicine Kyung Hee Univ.

• Na Ho‐jeong

  Dep. Of Pharmacology Coll. Of Oriental Medicine Inst. Of Oriental Medicine Kyung Hee Univ.

• Kim Hong‐joon

  Department Of Veterinary Medicine College Of Life Sciences Research Institute For Subtropical Agricu

• An Nyeon-hyoung

  College Of Pharmacy School Of Oriental Medicine Wonkwang University

• Kim Jong-hwan

  Department Of Electrical And Electronic Engineering College Of Engineering Yonsei University

• Chae Hang-Jung

  Department of Dental Pharmacology and Wonkwang Dental Research Institute, School of Dentistry, Wonkwang University

• Kim Hyung-Ryong

  Department of Dental Pharmacology and Wonkwang Biomaterial Implant Research Institute, School of Dentistry, Wonkwang University

• Kim Jong-Hwan

  Department of Electrical & Electronic Engineering, College of Engineering, Yonsei University, 134 Shinchon-dong, Seodaemoon-ku, Seoul 120-749, Korea

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