Cherng YG |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=2.437 ------>paper_class3=2 ------>paper_class2=1 ------>vol=26 ------>confirm_bywho=tlc ------>insert_bywho=chc ------>Jurnal_Rank=10.4 ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=1026 ------>medlineContent= ------>unit=E0121 ------>insert_date=20081201 ------>iam=2 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN= ------>authors_c= ------>score=459 ------>journal_name=Journal of Orthopaedic Research ------>paper_name=Apoptotic insults to human chondrocytes induced by sodium nitroprusside are involved in sequential events, including cytoskeletal remodeling, phosphorylation of mitogen-activated protein kinase kinase kinase-1/c-Jun N-terminal kinase, and Bax-mitochondria ------>confirm_date=20081202 ------>tch_id=089055 ------>pmid=18306405 ------>page1=1018 ------>fullAbstract=Nitric oxide (NO) can regulate chondrocyte activities. This study was aimed to evaluate the molecular mechanisms of NO donor sodium nitroprusside (SNP)-induced insults to human chondrocytes. Exposure of human chondrocytes to SNP increased cellular NO levels but decreased cell viability in concentration- and time-dependent manners. SNP time dependently induced DNA fragmentation and cell apoptosis. Treatment with 2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl 3-oxide, an NO scavenger, significantly lowered SNP-induced cell injuries. Administration of SNP interrupted F-actin and microtubule cytoskeletons and stimulated phosphorylation of mitogen-activated protein kinase kinase kinase-1 (MEKK1) and c-Jun N-terminal kinase (JNK). Similar to SNP, cytochalasin D, an inhibitor of F-actin formation, disturbed F-actin polymerization and increased MEKK1 and JNK activations. Overexpression of a dominant negative mutant of MEKK1 (dnMEK1) in human chondrocytes significantly ameliorated SNP-induced cell apoptosis. Exposure to SNP promoted Bax translocation from the cytoplasm to mitochondria, but application of dnMEKK1 lowered the translocation. SNP time dependently decreased the mitochondrial membrane potential, complex I NADH dehydrogenase activity, and cellular ATP levels, but increased the release of cytochrome c from mitochondria to the cytoplasm. Activities of caspase-9, -3, and -6 were sequentially increased by SNP administration. This study shows that SNP can induce apoptosis of human chondrocytes through sequential events, including cytoskeletal remodeling, activation of MEKK1/JNK, Bax translocation, mitochondrial dysfunction, cytochrome c release, caspase activation, and DNA fragmentation. ------>tmu_sno=None ------>sno=20270 ------>authors2=Chang HC ------>authors3=Lin YL ------>authors4=Kuo ML ------>authors5=Chiu WT ------>authors6=Chen RM ------>authors6_c= ------>authors=Cherng YG ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=Apoptotic insults to human chondrocytes induced by sodium nitroprusside are involved in sequential events, including cytoskeletal remodeling, phosphorylation of mitogen-activated protein kinase kinase kinase-1/c-Jun N-terminal kinase, and Bax-mitochondria-mediated caspase activation. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2008 ------>submit_flag=None ------>publish_month=1 |