Inhibition of Nrf2/HO-1 signaling pathway exacerbates Copper homeostasis in cerebral ischemia

Ischemic stroke is the third leading cause of death in the world, and oxidative stress is the key pathological mechanism of cerebral ischemia. The Nrf2/HO-1 signaling pathway is an endogenous defense system that regulates oxidative stress in the brain, and is involved in the imbalance regulation of copper homeostasis. The brain is one of the main target organs for copper accumulation, and copper is involved in the formation of myelin sheaths and the regulation of synaptic activity and signaling cascades. Imbalance of copper homeostasis leads to metabolic abnormalities and toxic effects on cells, and the mechanisms involved in cerebral ischemic injury are unknown. In this study, we found for the first time that the expression of copper homeostatic imbalance markers was elevated after cerebral ischemia, and the silencing of Nrf2 promoted the further elevation of copper homeostatic imbalance-related markers, which suggests that copper homeostatic imbalance is involved in the pathological process of cerebral ischemic neurological injury and that Nrf2/HO-1 signaling pathway is closely related to copper homeostatic imbalance in cerebral ischemia. Our study provides an experimental basis for further investigation of cuproptosis in cerebral ischemia.