Gastrodin activates the AMPK signaling pathway by inhibiting PRMT1 to alleviate cerebral ischemia-reperfusion injury.
TL;DR
It is demonstrated that gastrodin activates AMPK signaling by inhibiting PRMT1 protein expression in BMECs, thereby improving ferroptosis and dysfunction in BMECs and alleviating CIRI.
Abstract
The complexity of the pathological processes of cerebral ischemia-reperfusion injury (CIRI) has far impeded the success of current treatment methods. This study investigated whether gastrodin, the primary bioactive metabolite of Gastrodia elata Blume, alleviates CIRI by modulating brain microvascular endothelial cell (BMEC) function. Mice were subjected to transient middle cerebral artery occlusion (tMCAO), and human BMECs were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) for modeling. Gastrodin improved OGD/R-induced oxidative stress and ferroptosis in BMECs dose-dependently and promoted the migration and angiogenesis of BMECs. Protein arginine N-methyltransferase 1 (PRMT1) was a downstream protein of gastrodin in BMECs, and gastrodin accelerated its degradation by mediating PRMT1 protein instability. Exogenous overexpression of PRMT1 compromised the protective effect of gastrodin in vitro and in vivo. Gastrodin activated AMP-activated protein kinase (AMPK) signaling in BMECs in a PRMT1-dependent manner, and the AMPK signaling inhibitor dorsomorphin weakened the protective effect of gastrodin. Our findings demonstrate that gastrodin activates AMPK signaling by inhibiting PRMT1 protein expression in BMECs, thereby improving ferroptosis and dysfunction in BMECs and alleviating CIRI.