KMID : 0043320030260110937
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Archives of Pharmacal Research 2003 Volume.26 No. 11 p.937 ~ p.942
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JNK/SAPK Is Required in Nitric Oxide-Induced Apoptosis in Osteoblasts
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Kang Young-Jin
Chae Soo-Wan
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Abstract
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Nitric oxide(NO) induces apoptosis in human osteoblasts. Treatment with exogenous NO donors, SNAP (S-Nitroso-N-acelylpenicillamine) and SNP (sodium nitroprusside), to MG-63 osteoblasts resulted in apoptotic morphological changes, as shown by a bright blue-fluorescent condensed nuclei and chromatin fragmentation by fluorescence microscope of Hoechst 33258-staining. The activities of caspase-9 and the subsequent caspase-3-like cysteine proteases were increased during NO-induced cell death. Pretreatment with Z-VAD-FMK (a pancaspase inhibitor) or Ac-DEVD-CHO (a specific caspase-3 inhibitor) abrogated the NO-induced cell death. The NO donor markedly activated JNK, a stress-activated protein kinase in the human osteoblasts. This study showed that the inhibition of the JNK pathway markedly reduced NO-induced cell death. But neither PD98059 (MEK inhibitor) nor SB203580 (p38 MAPK inhibitor) had any effect on NO-induced death. Taken together, these results suggest that JNK/SAPK may be related to NO-induced apoptosis in MG-63 human osteoblasts.
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KEYWORD
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Nitric oxide, S-Nitroso-N-acetylpenicillamine, Sodium nitroprusside, Apoptosis, MG-63 human osteoblasts
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