Cigarette smoke-induced autophagy is regulated by SIRT1-PARP-1-dependent mechanism: implication in pathogenesis of COPD.
Autophagy is a fundamental cellular process that eliminates long-lived proteins and damaged organelles through lysosomal degradation pathway. Cigarette smoke (CS)-mediated oxidative stress induces cytotoxic responses in lung cells. However, the role of autophagy and its mechanism in CS-mediated cytotoxic responses is not known. We hypothesized that NAD(+)-dependent deacetylase, sirtuin 1 (SIRT1) plays an important role in regulating autophagy in response to CS. CS exposure resulted in induction of autophagy in lung epithelial cells, fibroblasts and macrophages. Pretreatment of cells with SIRT1 activator resveratrol attenuated CS-induced autophagy whereas SIRT1 inhibitor, sirtinol, augmented CS-induced autophagy. Elevated levels of autophagy were induced by CS in the lungs of SIRT1 deficient mice. Inhibition of poly(ADP-ribose)-polymerase-1 (PARP-1) attenuated CS-induced autophagy via SIRT1 activation. These data suggest that the SIRT1-PARP-1 axis plays a critical role in the regulation of CS-induced autophagy and have important implications in understanding the mechanisms of CS-induced cell death and senescence.
Hwang
Jae-woong
JW
Department of Environmental Medicine, University of Rochester Medical Center, NY, USA.
Chung
Sangwoon
S
Sundar
Isaac K
IK
Yao
Hongwei
H
Arunachalam
Gnanapragasam
G
McBurney
Michael W
MW
Rahman
Irfan
I
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002460:Cell Line; D016922:Cellular Senescence / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D056564:Sirtuin 1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012906:Smoke / Q000009:adverse effects; D012907:Smoking / Q000009:adverse effects*
D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012906:Smoke; C499320:PARP1 protein, human; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C447939:SIRT1 protein, human; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1