Back to Search
Start Over
Resveratrol attenuates vascular endothelial inflammation by inducing autophagy through the cAMP signaling pathway.
- Source :
-
Autophagy [Autophagy] 2013 Dec; Vol. 9 (12), pp. 2033-45. Date of Electronic Publication: 2013 Sep 30. - Publication Year :
- 2013
-
Abstract
- Inflammation participates centrally in all stages of atherosclerosis (AS), which begins with inflammatory changes in the endothelium, characterized by expression of the adhesion molecules. Resveratrol (RSV) is a naturally occurring phytoalexin that can attenuate endothelial inflammation; however, the exact mechanisms have not been thoroughly elucidated. Autophagy refers to the normal process of cell degradation of proteins and organelles, and is protective against certain inflammatory injuries. Thus, we intended to determine the role of autophagy in the antiinflammatory effects of RSV in human umbilical vein endothelial cells (HUVECs). We found that RSV pretreatment reduced tumor necrosis factor ? (TNF/TNF?)-induced inflammation and increased MAP1LC3B2 (microtubule-associated protein 1 light chain 3 ? 2) expression and SQSTM1/p62 (sequestosome 1) degradation in a concentration-dependent manner. A bafilomycin A 1 (BafA1) challenge resulted in further accumulation of MAP1LC3B2 in HUVECs. Furthermore, autophagy inhibitors 3-methyladenine (3-MA), chloroquine as well as ATG5 and BECN1 siRNA significantly attenuated RSV-induced autophagy, which, subsequently, suppressed the downregulation of RSV-induced inflammatory factors expression. RSV also increased cAMP (cyclic adenosine monophosphate) content, the expression of PRKA (protein kinase A) and SIRT1 (sirtuin 1), as well as the activity of AMPK (AMP-activated protein kinase). RSV-induced autophagy in HUVECs was abolished in the presence of inhibitors of ADCY (adenylyl cyclase, KH7), PRKA (H-89), AMPK (compound C), or SIRT1 (nicotinamide and EX-527), as well as ADCY, PRKA, AMPK, and SIRT1 siRNA transfection, indicating that the effects of RSV on autophagy induction were dependent on cAMP, PRKA, AMPK and SIRT1. In conclusion, RSV attenuates endothelial inflammation by inducing autophagy, and the autophagy in part was mediated through the activation of the cAMP-PRKA-AMPK-SIRT1 signaling pathway.
- Subjects :
- Adenine analogs & derivatives
Adenine pharmacology
Adenylyl Cyclase Inhibitors
Adenylyl Cyclases physiology
Carbazoles pharmacology
Endothelium, Vascular pathology
Human Umbilical Vein Endothelial Cells drug effects
Human Umbilical Vein Endothelial Cells physiology
Humans
Inflammation metabolism
Inflammation physiopathology
Isoquinolines pharmacology
Resveratrol
Signal Transduction drug effects
Signal Transduction physiology
Sirtuin 1 antagonists & inhibitors
Sirtuin 1 physiology
Sulfonamides pharmacology
Tumor Necrosis Factor-alpha pharmacology
Vasculitis metabolism
Vasculitis physiopathology
Vasculitis prevention & control
Autophagy drug effects
Cyclic AMP metabolism
Endothelium, Vascular drug effects
Inflammation prevention & control
Stilbenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1554-8635
- Volume :
- 9
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Autophagy
- Publication Type :
- Academic Journal
- Accession number :
- 24145604
- Full Text :
- https://doi.org/10.4161/auto.26336