Shear stress regulates cystathionine γ lyase expression to preserve endothelial redox balance and reduce membrane lipid peroxidation

Publication date: Available online 13 November 2019Source: Redox BiologyAuthor(s): Sofia-Iris Bibli, Jiong Hu, Matthias S. Leisegang, Janina Wittig, Sven Zukunft, Andrea Kapasakalidi, Beate Fisstlhaller, Diamantis Tsilimigras, Georgios Zografos, Konstantinos Filis, Ralf P. Brandes, Andreas Papapetropoulos, Fragiska Sigala, Ingrid FlemingAbstractCystathionine γ lyase (CSE) is the major source of hydrogen sulfide-derived species (H2Sn) in endothelial cells and plays an important role in protecting against atherosclerosis. Here we investigated the molecular mechanisms underlying the regulation of CSE expression in endothelial cells by fluid shear stress/flow. Fluid shear stress decreased CSE expression in human and murine endothelial cells and was negatively correlated with the transcription factor Krüppel-like factor (KLF) 2. CSE was identified as a direct target of the KLF2-regulated microRNA, miR-27b and high expression of CSE in native human plaque-derived endothelial cells, was also inversely correlated with KLF2 and miR-27b levels. One consequence of decreased CSE expression was the loss of Prx6 sulfhydration (on Cys47), which resulted in Prx6 hyperoxidation, decamerization and inhibition, as well as a concomitant increase in endothelial cell reactive oxygen species and lipid membrane peroxidation. H2Sn supplementation in vitro was able to reverse the redox state of Prx6. Statin therapy, which is known to activate KLF2, also decreased CSE expression but increased CSE act...
Source: Redox Biology - Category: Biology Source Type: research