COA-Cl Evokes Protective Responses Against H 2 O 2 -and 6-OHDA-Induced Toxic Injury in PC12 Cells

• Published in: Neurotoxicity research Vol. 40; no. 6; p. 2061
• Main Authors: Jamal, Mostofa, Tsukamoto, Ikuko, Maki, Takata, Takei, Sella, Konishi, Ryoji, Kinoshita, Hiroshi
• Format: Journal Article
• Language: English
• Published: United States 01.12.2022
• Subjects: Animals; Antioxidants - pharmacology; Apoptosis; bcl-2-Associated X Protein; Cell Survival; Hydrogen Peroxide - toxicity; Neuroprotective Agents - pharmacology; Oxidative Stress; Oxidopamine - toxicity; PC12 Cells; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; Oxidative stress; Hydrogen peroxide; 6-Hydroxydopamine; COA-Cl; PC12 cells
• ISSN: 1476-3524

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 O )- 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 O or 6-OHDA (200 μM) for 24 h. Treatment with COA-Cl attenuated the decrease in cell viability, SOD activity and the Bcl-2/Bax ratio caused by H O . In addition, COA-Cl attenuated the increase in LDH release, ROS production, caspase-3 activity, and apoptosis induced by H O . Further, COA-Cl enhanced the protection of 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 first to demonstrate that COA-Cl potentially protects PC12 cells against toxicity induced by H O and 6-OHDA, implying that COA-Cl could be a promising neuroprotective agent for the treatment of Parkinson's disease.