Mitochondrial complex III is involved in proapoptotic BAK-induced microvascular endothelial cell hyperpermeability

Shock
Ed W ChildsNichole D Liggins

Abstract

It has been shown that the intrinsic mitochondrial apoptotic cascade is activated in vascular hyperpermeability after conditions such as hemorrhagic shock. Studies from our laboratory demonstrated mitochondrial reactive oxygen species (ROS) formation in endothelial cells during vascular hyperpermeability. We hypothesized that the participation of mitochondrial ROS in the intrinsic apoptotic cascade results in microvascular endothelial cell hyperpermeability. The purpose of this study was to identify the site(s) of ROS formation in the mitochondrial complex(es) that leads to hyperpermeability. Rat lung microvascular endothelial cell monolayers were pretreated with inhibitors of the complex(es) (I-V) before the activation of the mitochondrial apoptotic cascade using the proapoptotic peptide BAK (BH3). Inhibitors of the xanthine oxidase, nicotinamide adenine dinucleotide phosphate (reduced form) oxidase, NOS, and cytochrome P-450 monooxygenase were also studied. The hyperpermeability was determined by the fluorescence of fluorescein isothiocyanate-albumin that leaked across endothelial cells and ROS production by 2',7& rime;-dichlorofluorescein diacetate. Cytochrome c levels were also measured. BAK (BH3)-transfected cells showed i...Continue Reading

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Citations

Sep 22, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Derek A Drechsel, Manisha Patel
Apr 17, 2008·Shock·Daniel G Remick
Jun 10, 2010·Clinical and Experimental Pharmacology & Physiology·Binu TharakanEd W Childs
Nov 14, 2014·Journal of Physiology and Biochemistry·Devendra A SawantEd W Childs
Oct 4, 2014·Journal of Cardiovascular Translational Research·Devendra A SawantEd W Childs
Jul 14, 2010·Leukemia Research·Anat Gafter-GviliTsipora Malachi
Sep 26, 2009·Free Radical Biology & Medicine·Florian L Muller
Jan 5, 2011·Nursing in Critical Care·Amanda R KnightJanet D Pierce
Jan 1, 2014·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Himakarnika AlluriBinu Tharakan

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