Preserving mitochondrial function by inhibiting GRP75 ameliorates neuron injury under ischemic stroke

Ischemic stroke is a life-threatening disease, which is closely related to neuron damage during ischemia. Mitochondrial dysfunction is essentially involved in the pathophysiological process of ischemic stroke. Mitochondrial calcium overload contributes to the development of mitochondrial dysfunction. However, the underlying mechanisms of mitochondrial calcium overload are far from being fully revealed. In the present study, middle cerebral artery obstruction (MCAO) was performed in vivo and oxygen and glucose deprivation (OGD) in vitro. The results indicated that both MCAO and OGD induced significant mitochondrial dysfunction in vivo and in vitro. The mitochondria became fragmented under hypoxia conditions, accompanied with upregulation of the heat shock protein 75 kDa glucose-regulated protein (GRP75). Inhibition of GRP75 was able to effectively ameliorate mitochondrial calcium overload and preserve mitochondrial function, which may provide evidence for further translational studies of ischemic diseases.

Automated summary

Ischemic stroke is closely related to mitochondrial dysfunction, with mitochondrial calcium overload playing a key role in the pathophysiological process. Inhibiting GRP75 can effectively ameliorate mitochondrial function and potentially provide evidence for translational studies of ischemic diseases.