Molecular Signaling Pathway in Manganese-Induced Neurotoxicity

Krishnan Prabhakaran
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Krishnan Prabhakaran: Department of Biology, Norfolk State University, USA

Biomedical Journal of Scientific & Technical Research, 2023, vol. 54, issue 1, 45390-45396

Abstract: Exposure to high levels of manganese [Mn] has been shown to cause a Parkinson’s-like syndrome known as ‘Manganism. Present study has attempted to elucidate the cellular and molecular pathways involved in manganese toxicity employing an immortalized dopaminergic cell line. Mn-treated cells exhibited a concentration-dependent apoptosis that was caspase dependent. Mn induced a rapid surge of intracellular reactive oxygen species [ROS] generation, followed by p38 mitogen-activated protein kinase [MAPK] activation and nuclear accumulation of hypoxia-inducible factor-1alpha [HIF-1alpha]. Activation of p38 MAPK and HIF1alpha accumulation were attenuated by N-acetyl-L-cysteine, GSH [antioxidants], 1400W [specific iNOS inhibitor], or a selective p38 MAPK inhibitor [SB203580]. Finally, RNAi knockdown of HIF-1 alpha protected the cells from Mn. These results indicate that Mn activated the HIF-1alpha-mediated signaling pathway which served as an initiator of Mn induced apoptosis in neuronal cells.

Keywords: Journals on Medical Drug and Therapeutics; Journals on Emergency Medicine; Physical Medicine and Rehabilitation; Journals on Infectious Diseases Addiction Science and Clinical Pathology; Open Access Clinical and Medical Journal; Journals on Biomedical Science; List of Open Access Medical Journal; Journals on Biomedical Engineering; Open Access Medical Journal; Biomedical Science Articles; Journal of Scientific and Technical Research (search for similar items in EconPapers)
Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:abf:journl:v:54:y:2023:i:1:p:45390-45396

DOI: 10.26717/BJSTR.2023.54.008490

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