Protective Effect of Norepinephrine, Dopamine and N-Methyldopamine Against Chemically-Induced Oxidative Ferroptosis in HT22 Neuronal Cells: Protein Disulfide Isomerase as a Mechanistic Target for Protection. (PubMed, Free Radic Biol Med) - Jun 3, 2025 - "In this study, we identify that three chemicals of the endogenous catecholamine family, i.e., norepinephrine, dopamine and N-methyldopamine, are capable of inhibiting PDI and can effectively protect against oxidative ferroptosis in cultured HT22 hippocampal neurons after challenged with different ferroptosis inducers, including erastin, RSL3, glutamate, sulfasalazine and l-buthionine-(S,R)-sulfoximine. Mechanistically, inhibition of PDI by norepinephrine, dopamine and N-methyldopamine or PDI knockdown by siRNAs each markedly reduces iNOS and nNOS activation (dimerization) and NO accumulation, and these changes are associated with reduced accumulation of cellular reactive oxygen species (ROS) and lipid-ROS and alleviation of chemically-induced ferroptotic neuronal death. Collectively, the findings of this study reveal that certain oxidative derivatives of catecholamine neurotransmitters, which may be highly cytotoxic, also possess the unique ability to rescue..."
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Bao Ting Zhu; Ming-Jie Hou; Qiushi Guo
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