The cell-permeable mitochondrial calcium uniporter inhibitor Ru265 preserves cortical neuron respiration after lethal oxygen glucose deprivation and reduces hypoxic/ischemic brain injury.

ABSTRACT: The mitochondrial calcium (Ca²⁺) uniporter (MCU) mediates high-capacity mitochondrial Ca²⁺ uptake implicated in ischemic/reperfusion cell death. We have recently shown that inducible MCU ablation in Thy1-expressing neurons renders mice resistant to sensorimotor deficits and forebrain neuron loss in a model of hypoxic/ischemic (HI) brain injury. These findings encouraged us to compare the neuroprotective effects of Ru360 and the recently identified cell permeable MCU inhibitor Ru265. Unlike Ru360, Ru265 (2-10 µM) reached intracellular concentrations in cultured cortical neurons that preserved cell viability, blocked the protease activity of Ca²⁺-dependent calpains and maintained mitochondrial respiration and glycolysis after a lethal period of oxygen-glucose

SUBMITTER: Novorolsky RJ 

PROVIDER: S-EPMC7238378 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature