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Redox signaling via oxidative inactivation of PTEN modulates pressure-dependent myogenic tone in rat middle cerebral arteries. PLoS One 2013;8(7):e68498

Date

07/19/2013

Pubmed ID

23861911

Pubmed Central ID

PMC3702596

DOI

10.1371/journal.pone.0068498

Scopus ID

2-s2.0-84879802004   15 Citations

Abstract

The present study examined the level of generation of reactive oxygen species (ROS) and roles of inactivation of the phosphatase PTEN and the PI3K/Akt signaling pathway in response to an increase in intramural pressure-induced myogenic cerebral arterial constriction. Step increases in intraluminal pressure of cannulated cerebral arteries induced myogenic constriction and concomitant formation of superoxide (O2 (.-)) and its dismutation product hydrogen peroxide (H2O2) as determined by fluorescent HPLC analysis, microscopic analysis of intensity of dihydroethidium fluorescence and attenuation of pressure-induced myogenic constriction by pretreatment with the ROS scavenger 4,hydroxyl-2,2,6,6-tetramethylpiperidine1-oxyl (tempol) or Mito-tempol or MitoQ in the presence or absence of PEG-catalase. An increase in intraluminal pressure induced oxidation of PTEN and activation of Akt. Pharmacological inhibition of endogenous PTEN activity potentiated pressure-dependent myogenic constriction and caused a reduction in NPo of a 238 pS arterial KCa channel current and an increase in [Ca(2+)]i level in freshly isolated cerebral arterial muscle cells (CAMCs), responses that were attenuated by Inhibition of the PI3K/Akt pathway. These findings demonstrate an increase in intraluminal pressure induced increase in ROS production triggered redox-sensitive signaling mechanism emanating from the cross-talk between oxidative inactivation of PTEN and activation of the PI3K/Akt signaling pathway that involves in the regulation of pressure-dependent myogenic cerebral arterial constriction.

Author List

Gebremedhin D, Terashvili M, Wickramasekera N, Zhang DX, Rau N, Miura H, Harder DR

Author

David X. Zhang MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Calcium
Catalase
Enzyme Activation
Hydrogen Peroxide
Male
Middle Cerebral Artery
Muscle Contraction
Muscle, Smooth, Vascular
Oxidation-Reduction
Oxidative Stress
PTEN Phosphohydrolase
Polyethylene Glycols
Potassium Channels, Calcium-Activated
Pressure
Rats
Reactive Oxygen Species
Signal Transduction
Superoxides
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a