COA-Cl Evokes Protective Responses Against H2O2-and 6-OHDA-Induced Toxic Injury in PC12 Cells

Abstract

COA-Cl, a novel adenosine-like nucleic acid analog, has recently been shown to exert neuroprotective effects and to increase dopamine levels both in vivo and in vitro. Therefore, we hypothesized that COA-Cl could protect dopaminergic neurons against toxic insults. Thus, the present study aimed to investigate the protective effects of COA-Cl against hydrogen peroxide (H 2 O 2 )-and 6-hydroxydopamine (6-OHDA)induced toxicity in PC12 cells, and to elucidate the possible mechanisms. PC12 cells were incubated with COA-Cl (100 µM) with or without H 2 O 2 or 6-OHDA (200 µM) for 24 h. Exposure to H 2 O 2 resulted in a decrease in cell viability in a dose-dependent manner. H 2 O 2 enhanced lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) production and caspase-3 activity, and decreased superoxide dismutase (SOD) activity and the Bcl-2/Bax protein ratio. H 2 O 2 also triggered apoptosis as measured by TUNEL analysis. However, treatment with COA-Cl attenuated the decrease in cell viability, SOD activity and the Bcl-2/Bax ratio caused by H 2 O 2 . In addition, COA-Cl attenuated the increase in LDH release, ROS production, caspase-3 activity and apoptosis. 6-OHDA also dose-dependently decreased cell viability and the Bcl-2/Bax ratio, and increased LDH release. However, COA-Cl greatly protected PC12 cells against the toxicity caused by 6-OHDA, as evidenced by an increase in cell viability and the Bcl-2/Bax ratio, and a decrease in LDH release. Our results are the rst to demonstrate that COA-Cl potentially protects PC12 cells against toxicity induced by H 2 O 2 and 6-OHDA, implying that COA-Cl could be a promising neuroprotective agent for the treatment of Parkinson's disease.