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JNK/SAPK Is Required in Nitric Oxide-Induced Apoptosis in Osteoblasts  

Kang, Young-Jin (Department of Pharmacology, College of Medicine, Gyeongsang National University, Institute of Health Science)
Chae, Soo-Wan (Department of Pharmacology and Institute of Cardiovascular Research, Chonbuk National University Medical School)
Publication Information
Archives of Pharmacal Research / v.26, no.11, 2003 , pp. 937-942 More about this Journal
Abstract
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.
Keywords
Nitric oxide; S-Nitroso-N-acetylpenicillamine; Sodium nitroprusside; Apoptosis; MG-63 human osteoblasts;
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