title: Resveratrol induces Sirt1-dependent apoptosis in 3T3-L1 preadipocytes by activating AMPK and suppressing AKT activity and survivin expression.
abstract: Resveratrol is a natural polyphenolic compound with anti-inflammatory, antioxidant and neuroprotective properties, and it serves as a chemopreventive and chemotherapeutic agent. However, only very limited data have been obtained regarding the effects of resveratrol on preadipocytes, and the mechanisms of these effects remain largely unknown. In this study, murine 3T3-L1 preadipocytes were incubated with resveratrol, and cell apoptosis was investigated. Resveratrol caused S-phase arrest to inhibit cell proliferation and significantly increased the lactate dehydrogenase leaking ratio. Hoechst 33258 staining and transmission electron microscopy revealed the ultrastructural changes in nuclear chromatins of apoptotic cells. Furthermore, resveratrol activated the mitochondrial signaling with decreases in the mitochondrial membrane potential, cytochrome c release and the activation of caspase 9 and caspase 3. Resveratrol treatment also increased the protein level of Sirt1. By using small interfering RNAs of Sirt1, adenosine-monophosphate-activated protein kinase (AMPK) α, survivin and the AMPK agonist (5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside) and specific inhibitors for protein kinase B (AKT) or caspases, it was demonstrated that activation of Sirt1 inhibited AKT activation and further decreased the expression of survivin. It could also increase AMPK activation. Both signaling pathways activated mitochondrion-mediated pathway. Our findings clarified the apoptotic effects of resveratrol in 3T3-L1 preadipocytes and revealed the involved pathway including AMPK, AKT and survivin, suggesting its potential therapeutic application in the treatment or prevention of obesity and related metabolic symptoms.
authors.affiliation: Guangzhou Center for Disease Control and Prevention, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Sifan
authors.initials: S
authors.lastname: Chen
authors.forename: Xincai
authors.initials: X
authors.lastname: Xiao
authors.forename: Xiang
authors.initials: X
authors.lastname: Feng
authors.forename: Wenxue
authors.initials: W
authors.lastname: Li
authors.forename: Niman
authors.initials: N
authors.lastname: Zhou
authors.forename: Lin
authors.initials: L
authors.lastname: Zheng
authors.forename: Yanshuang
authors.initials: Y
authors.lastname: Sun
authors.forename: Zili
authors.initials: Z
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D052438:Adipocytes, White / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors / Q000494:pharmacology; D020169:Caspases / Q000737:chemistry / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D020868:Gene Silencing; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000077185:Resveratrol; D016196:S Phase / Q000187:drug effects; D015290:Second Messenger Systems / Q000187:drug effects*; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology*; D000077022:Survivin; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; C117749:Birc5 protein, mouse; D061945:Caspase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D013267:Stilbenes; D000077022:Survivin; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; D020169:Caspases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D000077185:Resveratrol