title: Strategy to Suppress Oxidative Damage-Induced Neurotoxicity in PC12 Cells by Curcumin: the Role of ROS-Mediated DNA Damage and the MAPK and AKT Pathways.
abstract: Oxidative damage plays a key role in causation and progression of neurodegenerative diseases. Inhibition of oxidative stress represents one of the most effective ways in treating human neurologic diseases. Herein, we evaluated the protective effect of curcumin on PC12 cells against H2O2-induced neurotoxicity and investigated its underlying mechanism. The results indicated that curcumin pre-treatment significantly suppressed H2O2-induced cytotoxicity, inhibited the loss of mitochondrial membrane potential (Δψm) through regulation of Bcl-2 family expression, and ultimately reversed H2O2-induced apoptotic cell death in PC12 cells. Attenuation of caspase activation, poly(ADP-ribose) polymerase (PARP) cleavage, DNA damage, and accumulation of reactive oxygen species (ROS) all confirmed its protective effects. Moreover, curcumin markedly alleviated the dysregulation of the MAPK and AKT pathways induced by H2O2. Taken together, our findings suggest that the strategy of using curcumin could be a highly effective way in combating oxidative damage-mediated human neurodegenerative diseases.
authors.affiliation: School of Basic Medicine, Taishan Medical University, Taian, 271000, Shandong, China.|Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Fu
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: Department of Neurosurgery, Huxi Hospital, Jining Medical University, Shanxian, 274300, Shandong, China.
authors.forename: Ming-Zhi
authors.initials: MZ
authors.lastname: Cao
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Li
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Xiao-Yi
authors.initials: XY
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: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Zong-Yong
authors.initials: ZY
authors.lastname: Zhang
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Lei-Lei
authors.initials: LL
authors.lastname: Mao
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.
authors.forename: Feng-Ze
authors.initials: FZ
authors.lastname: Wang
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China.|Department of Neurology and Center of Cerebrovascular Disease Research, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China. tsmc_nks@tsmc.edu.cn.
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. blsun@tsmc.edu.cn.|Department of Neurology, Affiliated Hospital of Taishan Medical University, Taian, 271000, Shandong, China. blsun@tsmc.edu.cn.
authors.forename: Bao-Liang
authors.initials: BL
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004249:DNA Damage; D006861:Hydrogen Peroxide / Q000633:toxicity; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008954:Models, Biological; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D009498:Neurotoxins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; D003474:Curcumin
keywords: Apoptosis; Curcumin; Neurodegenerative diseases; Oxidative damage; Reactive oxygen species