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

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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 (H2O2)- 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 H2O2 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 H2O2. In addition, COA-Cl attenuated the increase in LDH release, ROS production, caspase-3 activity, and apoptosis induced by H2O2. 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 H2O2 and 6-OHDA, implying that COA-Cl could be a promising neuroprotective agent for the treatment of Parkinson’s disease.

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Authors and Affiliations

  1. Department of Forensic Medicine, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan

    Mostofa Jamal, Sella Takei & Hiroshi Kinoshita

  2. Department of Pharmaco-Bio-Informatics, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Ikuko Tsukamoto, Takata Maki & Ryoji Konishi

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  1. Mostofa Jamal
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  2. Ikuko Tsukamoto
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All authors whose names appear on the submission (1) made substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data, or the creation of new software used in the work; (2) drafted the work or revised it critically for important intellectual content; (3) approved the version to be published; and (4) agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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12640_2022_587_MOESM1_ESM.ppt

Supplementary file1 (PPT 335 KB) Fig. 7 Full gels for all Western blot images used for quantification in Fig. 4

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Jamal, M., Tsukamoto, I., Maki, T. et al. COA-Cl Evokes Protective Responses Against H2O2-and 6-OHDA-Induced Toxic Injury in PC12 Cells. Neurotox Res 40, 2061–2071 (2022). https://doi.org/10.1007/s12640-022-00587-3

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