title: Senegenin Inhibits Hypoxia/Reoxygenation-Induced Neuronal Apoptosis by Upregulating RhoGDIα.
abstract: Neuronal apoptosis is an important event in hypoxia/reoxygenation (H/R)-induced neuronal injury. Senegenin (Sen), the predominant and most active component in Radix Polygalae root extracts, displays anti-apoptotic and anti-oxidative properties. Sen protects against H/R-induced neuronal apoptosis of highly differentiated PC12 cells and primary cortical neurons. Sen has also been investigated as a source of potential therapeutic targets. In this study, a proteomic approach was used to identify Sen-regulated proteins in PC12 cells. We found that Sen protected against H/R-induced neuronal apoptosis by upregulating RhoGDIα protein expression. The regulatory functions of RhoGDIα were investigated by knocking down RhoGDIα expression in PC12 cells using small interfering RNA (siRNA), followed by quantification of apoptosis and then altering the expression levels of apoptosis-related proteins. Our data show that after silencing RhoGDIα, the neuroprotective effects of Sen on H/R-induced PC12 cell apoptosis were absent. Furthermore, RhoGDIα silencing alleviated the Sen-mediated inhibition of the JNK pathway. Therefore, these findings indicated that Sen attenuates H/R-induced neuronal apoptosis by upregulating RhoGDIα expression and inhibiting the JNK pathway. In addition to the mechanism underlying neuroprotective effects of Sen, RhoGDIα was identified as a putative target of Sen based on a primary rat cortical neuron model of H/R-induced injury.
authors.affiliation: Department of Pathophysiology, Key Laboratory of State Administration of Traditional Chinese Medicine of the People's Republic of China, School of Medicine, Jinan University, No. 601 Huangpu Avenue West, 510632, Guangzhou, Guangdong, China.|Department of Pathology, Municipal People's Hospital, 243000, Maanshan, Anhui, China.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Key Laboratory of State Administration of Traditional Chinese Medicine of the People's Republic of China, School of Medicine, Jinan University, No. 601 Huangpu Avenue West, 510632, Guangzhou, Guangdong, China.
authors.forename: Yandong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pathophysiology, Key Laboratory of State Administration of Traditional Chinese Medicine of the People's Republic of China, School of Medicine, Jinan University, No. 601 Huangpu Avenue West, 510632, Guangzhou, Guangdong, China.
authors.forename: Panhong
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Key Laboratory of State Administration of Traditional Chinese Medicine of the People's Republic of China, School of Medicine, Jinan University, No. 601 Huangpu Avenue West, 510632, Guangzhou, Guangdong, China.|Department of Gynecology, Clifford Hospital, 511495, Guangzhou, Guangdong, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Texas A & M University, College Station, TX 77843, USA.
authors.forename: Minyi
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology, Key Laboratory of State Administration of Traditional Chinese Medicine of the People's Republic of China, School of Medicine, Jinan University, No. 601 Huangpu Avenue West, 510632, Guangzhou, Guangdong, China.
authors.forename: Huadong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Key Laboratory of State Administration of Traditional Chinese Medicine of the People's Republic of China, School of Medicine, Jinan University, No. 601 Huangpu Avenue West, 510632, Guangzhou, Guangdong, China.
authors.forename: Daxiang
authors.initials: D
authors.lastname: Lu
authors.affiliation: Department of Pathophysiology, Key Laboratory of State Administration of Traditional Chinese Medicine of the People's Republic of China, School of Medicine, Jinan University, No. 601 Huangpu Avenue West, 510632, Guangzhou, Guangdong, China. tqirb@jnu.edu.cn.
authors.forename: Renbin
authors.initials: R
authors.lastname: Qi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D015687:Cell Hypoxia / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D061251:Primary Cell Culture; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D004365:Drugs, Chinese Herbal; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D016755:Proto-Oncogene Proteins c-jun; D034741:RNA, Small Interfering; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; C493220:tenuigenin; D048670:MAP Kinase Kinase 4; D010100:Oxygen
keywords: Hypoxia/reoxygenation; PC12 cells; Primary cortical neurons; RhoGDIα; Senegenin