title: Bone morphogenic protein-7 contributes to cerebral ischemic preconditioning induced-ischemic tolerance by activating p38 mitogen-activated protein kinase signaling pathway.
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.
authors.affiliation: Department of Neurosurgery, Shengjing Hospital, China Medical University, 36 Sanhao Street, Shenyang, 110004, People's Republic of China, junhong.guan@hotmail.com.
authors.forename: Junhong
authors.initials: J
authors.lastname: Guan
authors.forename: Han
authors.initials: H
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Lv
authors.forename: Duo
authors.initials: D
authors.lastname: Chen
authors.forename: Ye
authors.initials: Y
authors.lastname: Yuan
authors.forename: Shengtao
authors.initials: S
authors.lastname: Qu
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism*; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology*; D007093:Imidazoles / Q000737:chemistry; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology*; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D010766:Phosphorylation; D011725:Pyridines / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D007093:Imidazoles; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580