Vam3, a derivative of resveratrol, attenuates cigarette smoke-induced autophagy.
OBJECTIVE
To appraise the efficacy of Vam3 (Amurensis H), a dimeric derivative of resveratrol, at inhibiting cigarette smoke-induced autophagy.


METHODS
Human bronchial epithelial cells were treated with cigarette smoke condensates, and a chronic obstructive pulmonary disease (COPD) model was established by exposing male BALB/c mice to cigarette smoke. The protein levels of the autophagic marker microtubule-associated protein 1A/1B-light chain 3 (LC3), Sirtuin 1 (Sirt1), and foxhead box O 3a (FoxO3a) were examined using Western blotting and Immunohistochemistry. LC3 punctae were detected by immunofluorescence. The levels of FoxO3a acetylation were examined by immunoprecipitation. The level of intracellular oxidation was assessed by detecting ROS and GSH-Px.


RESULTS
Vam3 attenuated cigarette smoke condensate-induced autophagy in human bronchial epithelial cells, and restored the expression levels of Sirt1 and FoxO3a that had been reduced by cigarette smoke condensates. Similar protective effects of Vam3, reducing autophagy and restoring the levels of Sirt1 and FoxO3a, were observed in the COPD animal model. Additionally, Vam3 also diminished the oxidative stress that was induced by the cigarette smoke condensates.


CONCLUSIONS
Vam3 decreases cigarette smoke-induced autophagy via up-regulating/restoring the levels of Sirt1 and FoxO3a and inhibiting the induced oxidative stress.
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Pharmaceutical, National Key Laboratory of Natural Pharmaceutical Active Substance and Function, Beijing, China.
Ji
J
Shi
Ning
N
Yin
Ling-ling
LL
Xuan
Chun-suo
CS
Yao
Ai-min
AM
Meng
Qi
Q
Hou
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001343:Autophagy / Q000187:drug effects*; D001980:Bronchi / Q000166:cytology*; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects / Q000188:drug therapy / Q000378:metabolism*; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
D000975:Antioxidants; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D013267:Stilbenes; D056564:Sirtuin 1; D000077185:Resveratrol