Complex Effects of Putative DRP-1 Inhibitors on Stress Responses in Mouse Heart and Rat Cardiomyoblasts

2020
Written By CCRG

Wendt, L., Vider, J., Hoe, L., Du Toit, E., Peart, J. N., & Headrick, J. P. (2020). Complex Effects of Putative DRP-1 Inhibitors on Stress Responses in Mouse Heart and Rat Cardiomyoblasts. The Journal of pharmacology and experimental therapeutics, 372(1), 95–106. https://doi.org/10.1124/jpet.119.258897

Dynamin-related protein-1 (DRP-1)-dependent mitochondrial fission may influence cardiac tolerance to ischemic or oxidative stress, presenting a potential "cardioprotective" target. Effects of dynamin inhibitors [mitochondrial division inhibitor 1 (MDIVI-1) and dynasore] on injury, mitochondrial function, and signaling proteins were assessed in distinct models: ischemia-reperfusion (I-R) in mouse hearts and oxidative stress in rat H9c2 cardiomyoblasts. Hearts exhibited substantial cell death [approx. 40 IU lactate dehydrogenase (LDH) efflux] and dysfunction (approx. 40 mmHg diastolic pressure, approx. 40% contractile recovery) following 25 minutes' ischemia.

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