Shear stress regulates endothelial cell autophagy via redox regulation and Sirt1 expression
0301 basic medicine
Forkhead Box Protein O1
Intracellular Signaling Peptides and Proteins
Forkhead Transcription Factors
Protein Serine-Threonine Kinases
Autophagy-Related Protein 7
Mechanotransduction, Cellular
Autophagy-Related Protein 5
03 medical and health sciences
Gene Expression Regulation
Genes, Reporter
Hemorheology
Mutation
Autophagy
Human Umbilical Vein Endothelial Cells
Autophagy-Related Protein-1 Homolog
Diffusion Chambers, Culture
Humans
Original Article
Luciferases
Microtubule-Associated Proteins
Oxidation-Reduction
Cell Line, Transformed
DOI:
10.1038/cddis.2015.193
Publication Date:
2015-07-16T12:48:04Z
AUTHORS (10)
ABSTRACT
Disturbed cell autophagy is found in various cardiovascular disease conditions. Biomechanical stimuli induced by laminar blood flow have important protective actions against the development of vascular diseases. However, impacts and underlying mechanisms shear stress on autophagic process endothelial cells (ECs) are not entirely understood. Here we investigated human ECs. We that flow, but oscillatory or low-magnitude promoted autophagy. Time-course analysis cessation experiments confirmed this effect was a transient adaptive response appeared to be sustained physiological action. Flow had no mammalian target rapamycin-ULK pathway, whereas it significantly upregulated Sirt1 expression. Inhibition blunted stress-induced Overexpression wild-type Sirt1, deacetylase-dead mutant, sufficient induce Using both gain- loss-of-function experiments, showed Sirt1-dependent activation FoxO1 critical mediating Shear also deacetylation Atg5 Atg7. Moreover, expression were redox dependent, might act as redox-sensitive transducer reactive oxygen species-elicited Functionally, demonstrated flow-conditioned more resistant oxidant-induced injury, cytoprotective abolished after inhibition In summary, these results suggest Sirt1-mediated ECs may novel mechanism which produces its vascular-protective actions.
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