title: Sodium nitroprusside induces apoptosis of H9C2 cardiac muscle cells in a c-Jun N-terminal kinase-dependent manner.
abstract: Sodium nitroprusside (SNP) induces apoptosis in H9C2 cardiac muscle cells. Treatment with an exogenous NO donor SNP (2 mM) to H9C2 cells resulted in apoptotic morphological changes; a bright blue-fluorescent condensed nuclei and chromatin fragmentation by fluorescence microscope of Hoechst 33258-staining. The activity of caspase-3 like protease was increased during SNP-induced cell death. However, the activity of caspase-1 like protease was not affected by SNP. Pretreatment with Z-VAD-FMK (a pan-caspase inhibitor) or Ac-DEVD-CHO (a specific caspase-3 inhibitor) abrogated the SNP-induced cell death. SNP markedly activated three MAP kinases (JNK/SAPK, ERK and p38 MAP kinase) in the cardiac muscle cells. In this study, selective inhibition of the ERK or p38 MAPK pathway (by PD98059 or SB203580, respectively) had no effect on the extent of SNP-induced apoptosis in cardiac muscle cells. In contrast, inhibition of the JNK pathway by transfection of a dominant negative mutant of JNK markedly reduced the extent of SNP-induced cell death. Taken together, we suggest that JNK/SAPK will be related to SNP-induced apoptosis of H9C2 cardiac muscle cells.
authors.affiliation: Department of Pharmacology and Institute of Cardiovascular Research, Chonbuk National University, South Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Chae
authors.forename: H S
authors.initials: HS
authors.lastname: So
authors.forename: S W
authors.initials: SW
authors.lastname: Chae
authors.forename: J S
authors.initials: JS
authors.lastname: Park
authors.forename: M S
authors.initials: MS
authors.lastname: Kim
authors.forename: J M
authors.initials: JM
authors.lastname: Oh
authors.forename: Y T
authors.initials: YT
authors.lastname: Chung
authors.forename: S H
authors.initials: SH
authors.lastname: Yang
authors.forename: E T
authors.initials: ET
authors.lastname: Jeong
authors.forename: H M
authors.initials: HM
authors.lastname: Kim
authors.forename: R K
authors.initials: RK
authors.lastname: Park
authors.forename: H R
authors.initials: HR
authors.lastname: Kim
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020170:Caspase 1 / Q000378:metabolism; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009206:Myocardium / Q000166:cytology* / Q000201:enzymology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D014162:Transfection
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D003574:Cytochrome c Group; D020030:Nitric Oxide Donors; D009842:Oligopeptides; C099158:acetyl-aspartyl-glutamyl-valyl-aspartal; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D009599:Nitroprusside; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1