title: Cdk5 is required for the neuroprotective effect of transforming growth factor-β1 against cerebral ischemia-reperfusion.
abstract: Transforming Growth Factor β1 (TGF-β1), a well-known neuroprotective and neurotrophic factor in the central nervous system, is also involved in the repair process responses after ischemia-reperfusion injury. Herein, we found that TGF-β1 enhanced Cdk5 expression while decreased Tunel-positive cells compared with the ischemia group, and roscovitine(Cdk5 inhibitor) treatment could blunt these effects. In vitro study, TGF-β1 facilitated Cdk5/p35 complex, the proliferation, neurite growth and differentiation of PC12 cells, effects of which could be blunted by roscovitine and Cdk5 silencing. Moreover, ERK1/2 inhibitor SCH772984 abrogated the effects of TGF- β1 on Cdk5 and Bax levels. Taken together, we conclude that Cdk5 contributes to the neuroprotective function of TGF- β1 via ERK1/2 signaling.
authors.affiliation: Department of Physiology and Neurobiology, Xinxiang Medical University, China; Sino-UK Joint Laboratory of Brain Functions and Injury, Science and Technology Department of Henan Province, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Physiology and Neurobiology, Xinxiang Medical University, China; Sino-UK Joint Laboratory of Brain Functions and Injury, Science and Technology Department of Henan Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Toxicology, School of Public Health, Xinxiang Medical University, China.
authors.forename: Liyun
authors.initials: L
authors.lastname: Gao
authors.affiliation: College of Physical Education, Shanxi University, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Physiology and Neurobiology, Xinxiang Medical University, China.
authors.forename: Conglin
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Physiology and Neurobiology, Xinxiang Medical University, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of Physiology and Neurobiology, Xinxiang Medical University, China.
authors.forename: Xiaoqiu
authors.initials: X
authors.lastname: Luo
authors.affiliation: School of Life Science and Technology, Xinxiang Medical University, China. Electronic address: 141043@xxmu.edu.cn.
authors.forename: Xinshu
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007191:Indazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D034622:RNA Interference; D051381:Rats; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077546:Roscovitine; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D007191:Indazoles; D018696:Neuroprotective Agents; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011687:Purines; C587178:SCH772984; D053773:Transforming Growth Factor beta1; D051028:bcl-2-Associated X Protein; D000077546:Roscovitine; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse
keywords: Cdk5; Ischemia-reperfusion; PC12 cells; Roscovitine; TGF-β