Activation of p38 MAPK participates in brain ischemic tolerance induced by limb ischemic preconditioning by up-regulating HSP 70.
This study investigates whether activation of p38 MAPK by the up-regulation of HSP 70 participates in the induction of brain ischemic tolerance by limb ischemic preconditioning (LIP). Western blot and immunohistochemical assays indicated that p38 MAPK activation occurred earlier than HSP 70 induction in the CA1 region of the hippocampus after LIP. P-p38 MAPK expression was up-regulated at 6h and reached its peak 12h after LIP, while HSP 70 expression was not significantly increased until 1 day and peaked 2 days after LIP. Neuropathological evaluation by thionin staining showed that quercetin (4 ml/kg, 50mg/kg, intraperitoneal injection), an inhibitor of HSP 70, blocked the protective effect of LIP against delayed neuronal death that is normally induced by lethal brain ischemic insult, indicating that HSP 70 participates in the induction of brain ischemic tolerance by LIP. Furthermore, SB 203580, an inhibitor of HSP 70, inhibited HSP 70 activation in the CA1 region of the hippocampus induced by LIP either with or without the presence of subsequent brain ischemic insult. Based on the above results, it can be concluded that activation of p38 MAPK participates in the brain ischemic tolerance induced by LIP at least partly by the up-regulation of HSP 70 expression.
Sun
Xiao-Cai
XC
Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, PR China.
Xian
Xiao-Hui
XH
Li
Wen-Bin
WB
Li
Li
L
Yan
Cai-Zhen
CZ
Li
Qing-Jun
QJ
Zhang
Min
M
D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000473:pathology; D004198:Disease Susceptibility; D004789:Enzyme Activation; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D006614:Hindlimb / Q000098:blood supply*; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry; D019194:Ischemic Preconditioning; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D018840:HSP70 Heat-Shock Proteins; D007093:Imidazoles; D011725:Pyridines; D011794:Quercetin; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580