title: Effects of c-Jun N-terminal kinase on Activin A/Smads signaling in PC12 cell suffered from oxygen-glucose deprivation.
abstract: Activin A (Act A), a member of transforming growth factor-β (TGF-β) superfamily, is an early gene in response to cerebral ischemia. Growing evidences confirm the neuroprotective effect of Act A in ischemic injury through Act A/Smads signal activation. In this process, regulation networks are involved in modulating the outcomes of Smads signaling. Among these regulators, crosstalk between c-Jun N-terminal kinase (JNK) and Smads signaling has been found in the TGF-β induced epithelial-mesenchymal transition. However, in neural ischemia, the speculative regulation between JNK and Act A/Smads signaling pathways has not been clarified. To explore this issue, an Oxygen Glucose Deprivation (OGD) model was introduced to nerve-like PC12 cells. We found that JNK signal activation occurred at the early time of OGD injury (1 h). Act A administration suppressed JNK phosphorylation. In addition, JNK inhibition could elevate the strength of Smads signaling and attenuate neural apoptosis after OGD injury. Our results indicated a negative regulation effect of JNK on Smads signaling in ischemic injury. Taken together, JNK, as a critical site for neural apoptosis and negative regulator for Act A/Smads signaling, was presumed to be a molecular therapeutic target for ischemia.
authors.affiliation: Jilin University Department of Neurology, China-Japan Union Hospital Changchun China.
authors.forename: J Q
authors.initials: JQ
authors.lastname: Wang
authors.affiliation: Jilin University Clinical Medicine of Norman Bethune Medical Department Changchun China.
authors.forename: Z H
authors.initials: ZH
authors.lastname: Xu
authors.affiliation: Jilin University Department of Neurology, China-Japan Union Hospital Changchun China.
authors.forename: W Z
authors.initials: WZ
authors.lastname: Liang
authors.affiliation: Jilin University Department of Neurology, China-Japan Union Hospital Changchun China.
authors.forename: J T
authors.initials: JT
authors.lastname: He
authors.affiliation: Jilin University Department of Neurology, China-Japan Union Hospital Changchun China.
authors.forename: Y
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Jilin University Department of Neurology, China-Japan Union Hospital Changchun China.
authors.forename: H Y
authors.initials: HY
authors.lastname: Liu
authors.affiliation: Jilin University Department of Neurology, China-Japan Union Hospital Changchun China.
authors.forename: L X
authors.initials: LX
authors.lastname: Xue
authors.affiliation: Jilin University Key Laboratory for Molecular Enzymology & Engineering, The Ministry of Education Changchun China.
authors.forename: W
authors.initials: W
authors.lastname: Shi
authors.affiliation: Jilin University Department of Neurology, China-Japan Union Hospital Changchun China.
authors.forename: Y K
authors.initials: YK
authors.lastname: Shao
authors.affiliation: Jilin University Department of Neurology, China-Japan Union Hospital Changchun China mangjing@jlu.edu.cn.
authors.forename: J
authors.initials: J
authors.lastname: Mang
authors.affiliation: Jilin University Department of Neurology, China-Japan Union Hospital Changchun China xuzhongxin999@aliyun.com.
authors.forename: Z X
authors.initials: ZX
authors.lastname: Xu
mesh_terms: D028341:Activins / Q000494:pharmacology*; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D020932:Nerve Growth Factor / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D000873:Anthracenes; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C422405:activin A; D028341:Activins; C432165:pyrazolanthrone; D020932:Nerve Growth Factor; D048031:JNK Mitogen-Activated Protein Kinases; D005947:Glucose; D010100:Oxygen