Ferroptosis is an iron-dependent pathway of regulated cell death. But the exact mechanism of ferroptosis in ischemic stroke remains unclear. We hypothesize that conventional protein kinase cγ (cPKCγ) can attenuate neuronal death by regulating ferroptosis. In this study, primary cultured cortical neurons were used to establish 1 h oxygen-glucose deprivation (OGD) and reoxygenation (R) 0-12 h (i.e., 1 h OGD/R 0-12 h) as in vitro models of cell ischemia. After 1 h OGD/R 0-12 h, cyclooxygenase 2 (COX2) and acyl-CoA synthetase long-chain family member 4 (ACSL4) levels increased, and glutathione peroxidase 4 (GPx4) levels decreased significantly. Concurrently, GPx4 activity decreases, and iron levels increased. The inhibition of ferroptosis by Liproxstatin-1 ameliorated OGD-induced neuronal injury. Liproxstatin-1 administration prominently induced GPx4 expression and suppressed COX2 expression. Additionally, Liproxstatin-1 administration substantially reduced iron accumulation and rescued GPx4 activity, accompanying by prominent changes in lipid peroxidation indicators. cPKCγ knockdown significantly aggravated neuronal death, and increased GPx4 depletion and COX2 and ACSL4 levels, thus dramatically increasing iron accumulation and GPx4 inactivation. Changes in lipid peroxidation indicators were also significantly increased. Ferroptosis is closely associated with OGD-induced ischemic injury, and cPKCγ can attenuate ischemic injury after OGD via ferroptosis suppression.
Keywords: Conventional protein kinase cγ; Ferroptosis; Iron accumulation; Lipid peroxidation; Oxygen–glucose deprivation/reoxygenation.
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