title: Reversal of Beta-Amyloid-Induced Neurotoxicity in PC12 Cells by Curcumin, the Important Role of ROS-Mediated Signaling and ERK Pathway.
abstract: Progressive accumulation of beta-amyloid (Aβ) will form the senile plaques and cause oxidative damage and neuronal cell death, which was accepted as the major pathological mechanism to the Alzheimer's disease (AD). Hence, inhibition of Aβ-induced oxidative damage and neuronal cell apoptosis by agents with potential antioxidant properties represents one of the most effective strategies in combating human AD. Curcumin (Cur) a natural extraction from curcuma longa has potential of pharmacological efficacy, including the benefit to antagonize Aβ-induced neurotoxicity. However, the molecular mechanism remains elusive. The present study evaluated the protective effect of Cur against Aβ-induced cytotoxicity and apoptosis in PC12 cells and investigated the underlying mechanism. The results showed that Cur markedly reduced Aβ-induced cytotoxicity by inhibition of mitochondria-mediated apoptosis through regulation of Bcl-2 family. The PARP cleavage, caspases activation, and ROS-mediated DNA damage induced by Aβ were all significantly blocked by Cur. Moreover, regulation of p38 MAPK and AKT pathways both contributed to this protective potency. Our findings suggested that Cur could effectively suppress Aβ-induced cytotoxicity and apoptosis by inhibition of ROS-mediated oxidative damage and regulation of ERK pathway, which validated its therapeutic potential in chemoprevention and chemotherapy of Aβ-induced neurotoxicity.
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Cun-Dong
authors.initials: CD
authors.lastname: Fan
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Xiao-Ting
authors.initials: XT
authors.lastname: Fu
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Qing-Jian
authors.initials: QJ
authors.lastname: Wu
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Hou
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Ming-Feng
authors.initials: MF
authors.lastname: Yang
authors.affiliation: School of Basic Medicine, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Sun
authors.affiliation: School of Basic Medicine, Taishan Medical University, Taian, 271000, Shandong, China. fxy007800@163.com.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Fu
authors.affiliation: Departments of Rehabilitation, Taian Central Hospital, Taian, 271000, Shandong, China. zhengzc1965@126.com.
authors.forename: Zun-Cheng
authors.initials: ZC
authors.lastname: Zheng
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China. blsun88@163.com.
authors.forename: Bao-Liang
authors.initials: BL
authors.lastname: Sun
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); D003474:Curcumin
keywords: Apoptosis; Beta-amyloid; Curcumin; Neurotoxicity; Oxidative damage