Cookies help us deliver our services. By using our services, you agree to our use of cookies. More information

Rekuviene 2017 Neurosci Lett

From Bioblast
Publications in the MiPMap
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.

» PMID: 28527718

Rekuviene E, Ivanoviene L, Borutaite V, Morkuniene R (2017) Neurosci Lett

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 

2017-08