title: Role of PKC-delta during hypoxia in heart-derived H9c2 cells.
abstract: In the present study, we investigated the role of protein kinase C (PKC) isoforms during hypoxia in heart-derived H9c2 cells. Hypoxia caused a rapid translocation of PKC-delta from soluble to particulate fraction and a downregulation of PKC-epsilon and PKC-zeta, whereas PKC-alpha and PKC-beta I remained unaltered. When H9c2 cells were pretreated with PKC-delta inhibitor rottlerin (3 microM), hypoxia-induced apoptotic and necrotic cell death were significantly increased. Hypoxic insult also caused an activation of extracellular signal-regulated protein kinase (ERK) and p38 MAPK with no change in c-Jun NH(2)-terminal protein kinase (JNK) phosphorylation. Hypoxia-induced cell death was increased by treatment with ERK1/2 inhibitor U0126 (10 microM), but attenuated by p38 MAPK inhibitor SB202190 (10 microM). Treatment with rottlerin completely blocked the hypoxia-induced ERK phosphorylation, whereas it significantly increased p38 MAPK phosphorylation. The hypoxia-induced translocation of PKC-delta was not altered by U0126 and/or SB202190. From these results, it is suggested that hypoxia causes a rapid translocation of PKC-delta and subsequently ERK activation and p38 inactivation, rendering H9c2 cells resistant to hypoxia-induced cell death.
authors.affiliation: Department of Physiology, School of Medicine, Ajou University, Suwon 442-749, Korea.
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Kim
authors.forename: Chang-Hyun
authors.initials: CH
authors.lastname: Moon
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Min Hwa
authors.initials: MH
authors.lastname: Kim
authors.forename: Soo Hwan
authors.initials: SH
authors.lastname: Lee
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Baik
authors.forename: Yi-Sook
authors.initials: YS
authors.lastname: Jung
mesh_terms: D018929:Cell Culture Techniques; D016923:Cell Death; D015687:Cell Hypoxia; D006801:Humans; D048052:Mitogen-Activated Protein Kinase 3 / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology* / Q000201:enzymology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000494:pharmacology*; D051745:Protein Kinase C-delta
chemical_list: C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D048052:Mitogen-Activated Protein Kinase 3