Rekuviene 2017 Neurosci Lett
|Rekuviene E, Ivanoviene L, Borutaite V, Morkuniene R (2017) Rotenone decreases ischemia-induced injury by inhibiting mitochondrial permeability transition in mature brains. Neurosci Lett 653:45-50.
Abstract: The mitochondrial permeability transition pore (mPTP) is thought to be implicated in brain ischemia-induced cell death. Here we sought to determine whether complex I (CI) of the mitochondrial electron transfer-pathway may be involved in regulation of mPTP opening during ischemia and whether a specific inhibitor of this complex - rotenone can protect against ischemia-induced cell death in an experimental model of total ischemia in adult rat brains. Anesthetized Wistar rats were administered a single injection of rotenone (0.01mg/kg) to the tail vein and brains were removed and subjected to 120min ischemia. We found that intravenous injection of rotenone 20min before ischemia increased resistance to Ca2+-induced mPTP opening and decreased production of reactive oxygen species (ROS) in mitochondria isolated from ischemia-damaged cortex and cerebellum. Rotenone administration before ischemia decreased infarct size in both brain regions (cortex and cerebellum). Rotenone added directly to normal, non-ischemic cortical or cerebellar mitochondria increased their resistance to Ca2+-induced mPTP opening at concentration which fully inhibited NAD-dependent mitochondrial respiration. Our data demonstrate that rotenone used intravenously may be protective against acute brain ischemia-induced injuries by inhibition of mPTP opening and ROS production. These findings suggest that CI of mitochondrial electron transfer-pathway plays a role in mPTP regulation during cerebral ischemia in mature brains and that agents acting on CI activity may be clinically useful for stroke therapy.
Copyright © 2017 Elsevier B.V. All rights reserved. • Keywords: Brain ischemia, Cell death, Complex I, Mitochondrial permeability transition pore, ROS, Rotenone • Bioblast editor: Kandolf G • O2k-Network Lab: LT Kaunas Borutaite V
Labels: MiParea: Respiration, Pharmacology;toxicology
Stress:Ischemia-reperfusion, Permeability transition Organism: Rat Tissue;cell: Nervous system Preparation: Isolated mitochondria Enzyme: Complex I, Complex II;succinate dehydrogenase Regulation: Inhibitor
Pathway: N, S, NS HRR: Oxygraph-2k