ROS-independent preconditioning in neurons via activation of mitoK(ATP) channels by BMS-191095

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Tamás GáspárD W Busija

Abstract

Previously, we have shown that the selective mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel opener BMS-191095 (BMS) induces neuronal preconditioning (PC); however, the exact mechanism of BMS-induced neuroprotection remains unclear. In this study, we have identified key components of the cascade resulting in delayed neuronal PC with BMS using isolated rat brain mitochondria and primary cultures of rat cortical neurons. BMS depolarized isolated mitochondria without an increase in reactive oxygen species (ROS) generation and induced rapid phosphorylation of Akt and glycogen synthase kinase-3beta. Long-term (3 days) treatment of neurons with BMS resulted in sustained mitochondrial depolarization, decreased basal ROS generation, and elevated ATP levels. This treatment also elicited almost complete protection against glutamate excitotoxicity, which could be abolished using the phosphoinositide 3-kinase (PI3K) inhibitor wortmannin, but not with the superoxide dismutase (SOD) mimetic M40401. Long-term BMS treatment induced a PI3K-dependent increase in the expression and activity of catalase without affecting manganese SOD and copper/zinc-dependent SOD. Finally, the catalase inhibitor 3-aminotriazole dose-dependently antagon...Continue Reading

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Citations

Jan 5, 2011·Translational Stroke Research·Jeffrey M Gidday
Sep 2, 2010·Journal of Medicinal Chemistry·Fraser F FlemingBrian C Shook
Oct 31, 2008·American Journal of Physiology. Cell Physiology·Ferenc DomokiDavid W Busija
Mar 23, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Adam InstitorisDavid W Busija
Aug 24, 2012·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Manisha NautiyalDebra I Diz
Nov 14, 2008·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Prasad V G KatakamDavid W Busija
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May 31, 2011·Best Practice & Research. Clinical Anaesthesiology·Stacy L Fairbanks, Ansgar M Brambrink
Mar 10, 2016·Biochimica Et Biophysica Acta·Michał LaskowskiAdam Szewczyk
Jul 31, 2008·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Keita MayanagiDavid W Busija
Sep 2, 2015·Canadian Journal of Physiology and Pharmacology·Alexandra PetruşNorbert Jost
Mar 13, 2012·Biochimica Et Biophysica Acta·Anna Kajma, Adam Szewczyk
Dec 30, 2008·Biochimica Et Biophysica Acta·Mario ZorattiIldikò Szabò
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Dec 25, 2015·American Journal of Physiology. Renal Physiology·Bryan A WilsonMark C Chappell
Jun 16, 2014·American Journal of Physiology. Heart and Circulatory Physiology·Prasad V G KatakamDavid W Busija
Jun 16, 2009·Brain Research·Tamás GáspárDavid W Busija

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Methods Mentioned

BETA
Assay
scraping
electrophoresis
X-ray
Reverse Transcription-PCR
PCR

Software Mentioned

SPSS
SigmaStat
Zeiss

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