Regulation of H2S Production and H2S-Dependent Signal Transduction in Endothelial Cells by Shear Stress
Date Issued
2011
Date
2011
Author(s)
Chen, Chang-Ting
Abstract
Hydrogen sulfide (H2S) is a novel gasotransmitter in cardiovascular system, it renders multiple cardioprotective effects. Laminar shear stress is also a cardioprotective factor in cardiovascular system, which shares many similarities in downstream signal transduction pathways with H2S. However, knowledge about the regulation of H2S production by shear stress and the role of H2S in shear-induced signal transduction is still limited. In the present study, efforts were made to investigate the effect of shear stress on H2S production. Furthermore, the role of H2S in shear-induced cell signaling is also discussed.
In cardiovascular system, shear stress exerted by blood flow mainly affects vascular endothelial cells (ECs). Thus, human umbilical vein endothelial cells (HUVECs) and bovine aortic endothelial cells (BAECs) are used in present study. After laminar shear stress stimulation for 30 minutes, H2S production rate is enhanced by 5 fold in BAECs. Three enzymes possibly involved in H2S production—cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and 3-mercapto-sulfurtransferase (3-MST)—are not significantly affected by shear stress in terms of protein and mRNA level, implying the possibility that shear stress enhaces H2S production rate by increasing CSE, CBS, and 3-MST enzyme activities. In order to study the role of H2S in shear-induced cell signaling, CSE, CBS, and 3-MST were knocked down by siRNAs before HUVECs were stimulated by shear stress. Results show that shear-induced Akt phosphorylation is inhibited by CSE, CBS, and 3-MST siRNAs.
In conclusion, shear-induced cardioprotective effect might be partly a result of increased H2S concentration in ECs. Futrther, shear stress induces Akt phosphorylation in a H2S-dependent way.
Subjects
shear stress
hydrogen sulfide
endothelial cells
cardioprotective
Type
thesis
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