Curcumin I protects the dopaminergic cell line SH-SY5Y from 6-hydroxydopamine-induced neurotoxicity through attenuation of p53-mediated apoptosis

• Published in: Neuroscience letters Vol. 489; no. 3; pp. 192 - 196
• Main Authors: Jaisin, Yamaratee, Thampithak, Anusorn, Meesarapee, Benjawan, Ratanachamnong, Piyanee, Suksamrarn, Apichart, Phivthong-ngam, Laddawal, Phumala-Morales, Noppawan, Chongthammakun, Sukumal, Govitrapong, Piyarat, Sanvarinda, Yupin
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 11-02-2011; Elsevier
• Subjects: 6-OHDA; Apoptosis - drug effects; Bax/Bcl-2 ratio; bcl-2-Associated X Protein - metabolism; Biological and medical sciences; Cell Line, Tumor; Cell Survival - drug effects; Curcuma longa; Curcumin - pharmacology; Curcumin I; Dopamine - metabolism; Fundamental and applied biological sciences. Psychology; Humans; Nerve Degeneration - prevention & control; Neurons - drug effects; Neurons - pathology; Neuroprotective Agents - pharmacology; Neurotoxins - antagonists & inhibitors; Neurotoxins - pharmacology; Oxidopamine - antagonists & inhibitors; Oxidopamine - pharmacology; p53; Phosphorylation; Proto-Oncogene Proteins c-bcl-2 - metabolism; Reactive Oxygen Species - metabolism; ROS; Tumor Suppressor Protein p53 - metabolism; Vertebrates: nervous system and sense organs; 6-OHDA; ROS; Curcumin I; Bax/Bcl-2 ratio; p53; Dopamine; p53 Protein; Catecholamine; Oxidopamine; Neurotoxicity; Cell line; Cell death; Neurotransmitter; Curcumin; Apoptosis
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2010.12.014

▶ Curcumin I prevents 6-OHDA-induced oxidative-damage in SH-SY5Y cells. ▶ It inhibits 6-OHDA-induced increase in Bax/Bcl-2 ratio in dose-dependent manner. ▶ It suppresses the phosphorylation of p53. ▶ It may be used as adjunctive therapy in oxidative stress-induced neurodegeneration.
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.