title: Curcumin I protects the dopaminergic cell line SH-SY5Y from 6-hydroxydopamine-induced neurotoxicity through attenuation of p53-mediated apoptosis.
abstract: Oxidative stress (OS) plays a pivotal role in the pathogenesis of Parkinson's disease (PD). 6-Hydroxydopamine (6-OHDA) is a neurotoxin used to induce oxidative cell death of dopaminergic neurons in experimental models of PD. Curcumin I, or diferuloylmethane is a pure compound isolated from Curcuma longa Linn. that has been reported to have neuroprotective properties. The precise mechanism, however, remains unclear. This study aims to elucidate the mechanisms by which curcumin I exerts its effects, using 6-OHDA-induced neurotoxicity in the human dopaminergic cell line SH-SY5Y. In our experiments, pretreatment with curcumin I improved cell viability, and significantly reduced reactive oxygen species (ROS). Further investigations revealed a reduction of p53 phosphorylation and decrease of the Bax/Bcl-2 ratio, as measured by mRNA expression and protein level. Taken together, these findings indicate that curcumin I protects dopaminergic neurons from 6-OHDA-induced toxicity via the reduction of ROS production, and subsequent attenuation of p53 phosphorylation and reduction of the Bax/Bcl-2 ratio.
authors.affiliation: Department of Pharmacology, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand.
authors.forename: Yamaratee
authors.initials: Y
authors.lastname: Jaisin
authors.forename: Anusorn
authors.initials: A
authors.lastname: Thampithak
authors.forename: Benjawan
authors.initials: B
authors.lastname: Meesarapee
authors.forename: Piyanee
authors.initials: P
authors.lastname: Ratanachamnong
authors.forename: Apichart
authors.initials: A
authors.lastname: Suksamrarn
authors.forename: Laddawal
authors.initials: L
authors.lastname: Phivthong-Ngam
authors.forename: Noppawan
authors.initials: N
authors.lastname: Phumala-Morales
authors.forename: Sukumal
authors.initials: S
authors.lastname: Chongthammakun
authors.forename: Piyarat
authors.initials: P
authors.lastname: Govitrapong
authors.forename: Yupin
authors.initials: Y
authors.lastname: Sanvarinda
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D009410:Nerve Degeneration / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016627:Oxidopamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D009498:Neurotoxins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D016627:Oxidopamine; D003474:Curcumin; D004298:Dopamine