title: Regulation of stress-associated scaffold proteins JIP1 and JIP3 on the c-Jun NH2-terminal kinase in ischemia-reperfusion.
abstract: Ischemia-reperfusion (IR)-induced cell apoptosis involves the activation of c-Jun NH2-terminal kinase (JNK). The activation of JNK requires the presence of scaffold proteins called JNK-interacting proteins (JIP), which bind several members of a signaling cascade for proper signaling specificity. In this study, the expression of scaffold proteins JIP1 and JIP3 and their roles in the regulation of JNK activity were investigated in simulated IR in a cell model (H9c2). JIP1 protein expression was significantly decreased, whereas JIP3 protein expression was increased in IR H9c2 cells. Adenovirus-induced overexpression of JIP1 reduced IR-induced JNK activity and apoptosis. Conversely, overexpression of JIP3 increased JNK activity and apoptosis following IR. Depletion of endogenous JIP1 by siRNA treatment increased the IR-induced JNK activity, whereas siRNA-mediated depletion of endogenous JIP3 inhibited JNK activity. These results suggest that JIP1 and JIP3 play important roles in the activation of JNK during simulated IR challenge in H9c2 cells.
authors.affiliation: Centre for Research and Treatment of Atherosclerosis, University of Manitoba, Winnipeg, Canada.
authors.forename: Bing
authors.initials: B
authors.lastname: Xu
authors.forename: Yaling
authors.initials: Y
authors.lastname: Zhou
authors.forename: Karmin
authors.initials: K
authors.lastname: O
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Choy
authors.forename: Grant N
authors.initials: GN
authors.lastname: Pierce
authors.forename: Yaw L
authors.initials: YL
authors.lastname: Siow
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D004789:Enzyme Activation; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000201:enzymology*; D015425:Myocardial Reperfusion; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000502:physiology*; D034622:RNA Interference; D051381:Rats
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C110528:Mapk8ip1 protein, rat; D009419:Nerve Tissue Proteins; C554781:mapk8ip3 protein, rat; D048031:JNK Mitogen-Activated Protein Kinases