Bone Morphogenic Protein-7 Contributes to Cerebral Ischemic Preconditioning Induced-Ischemic Tolerance by Activating p38 Mitogen-Activated Protein Kinase Signaling Pathway |
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Authors: | Junhong Guan Han Li Tao Lv Duo Chen Ye Yuan Shengtao Qu |
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Institution: | 1. Department of Neurosurgery, Shengjing Hospital, China Medical University, 36 Sanhao Street, Shenyang, 110004, People’s Republic of China 2. Department of Emergency Medicine, Shengjing Hospital, China Medical University, Shenyang, 110004, People’s Republic of China
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Abstract: | Cerebral ischemic preconditioning (IPC), which refers to a transient and noninjurious ischemia is able to induce tolerance against the subsequent lethal ischemia, including ischemic stroke. We have previously reported that bone morphogenic protein-7 (BMP-7) contributes to the neuroprotective effects of IPC-induced ischemic tolerance, and thus ameliorates the following ischemia/reperfusion (I/R) injury in rats. Consequently, in the present study, we continued to explore the underlying regulatory mechanisms involved in BMP-7-mediated cerebral IPC in the rat model of ischemic tolerance. Male Wistar rats were preconditioned by 15-min middle cerebral artery occlusion (MCAO). After 2-day reperfusion, these animals were subjected to prolonged MCAO for 2 h. Our results showed that the phosphorylated p38 mitogen-activated protein kinase (MAPK) paralleling to BMP-7 was up-regulated by IPC in rat brain. Inactivation of p38 MAPK by pretreatment of SB203580, a p38 MAPK-specific suppressor, weakened the protective effect of IPC on CA1 neurons. Moreover, the enhanced phosphorylation of p38 MAPK induced by IPC was attenuated when the endogenous BMP-7 was inhibited by BMP-7 antagonist noggin. Besides, blockade of p38 MAPK signal transduction pathway via SB203580 abrogated the protective effects of exogenous BMP-7 against cerebral infraction. These present findings suggest that BMP-7 contributes to cerebral IPC-induced ischemic tolerance via activating p38 MAPK signaling pathway. |
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