title: Thymoquinone Inhibits Angiotensin II-Induced Proliferation and Migration of Vascular Smooth Muscle Cells Through the AMPK/PPARγ/PGC-1α Pathway.
abstract: The proliferation and migration of vascular smooth muscle cells (VSMCs) play crucial roles in the pathogenesis of diabetes and its complications. Thymoquinone (TQ) is the primary bioactive component of Nigella sativa L. seed oil, which exhibits antihyperglycemic effect in diabetic rats, but its role in VSMC proliferation and migration has not been investigated. The results of MTT assay and flow cytometry assay indicated that TQ dose-dependently inhibited angiotensin II (Ang II)-induced VSMCs' cell cycle progression, as well as cyclin D1 expression, whereas p21 expression was altered conversely. TQ dose-dependently suppressed Ang II-induced VSMC migration accompanied by reduced MMP-9 expression. In addition, we observed the elevated reactive oxygen species (ROS) generation and NADPH oxidase activity and reduced superoxide dismutase activity in Ang II-treated VSMCs, which were dose-dependently reversed by TQ. Western blot analysis indicated that TQ dose-dependently restored Ang II-inhibited expression of p-AMPK, PPARγ, and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) proteins. Furthermore, adenosine monophosphate-activated protein kinase (AMPK) inhibitor Compound C and PGC-1α siRNA transfection abrogated the activation of TQ on Ang II-inhibited AMPK/PPARγ/PGC-1α signaling, but abolished the inhibitory effects of TQ on Ang II-induced VSMC proliferation and migration, as well as ROS generation. Taken together, these results demonstrated that TQ inhibited Ang II-induced VSMC proliferation and migration through the AMPK/PPARγ/PGC-1α pathway.
authors.affiliation: 1 Department of Internal Medicine, Hong-Hui Hospital, Xi'an Jiaotong University , College of Medicine, Xi'an, People's Republic of China .
authors.forename: Xing
authors.initials: X
authors.lastname: Pei
authors.affiliation: 1 Department of Internal Medicine, Hong-Hui Hospital, Xi'an Jiaotong University , College of Medicine, Xi'an, People's Republic of China .
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Li
authors.affiliation: 2 Department of Endocrinology, Ankang City Central Hospital , Ankang, People's Republic of China .
authors.forename: Heming
authors.initials: H
authors.lastname: Chen
authors.affiliation: 1 Department of Internal Medicine, Hong-Hui Hospital, Xi'an Jiaotong University , College of Medicine, Xi'an, People's Republic of China .
authors.forename: Yong
authors.initials: Y
authors.lastname: Han
authors.affiliation: 1 Department of Internal Medicine, Hong-Hui Hospital, Xi'an Jiaotong University , College of Medicine, Xi'an, People's Republic of China .
authors.forename: Yigang
authors.initials: Y
authors.lastname: Fan
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D016227:Benzoquinones / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics* / Q000378:metabolism; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D016227:Benzoquinones; D050759:Cyclin-Dependent Kinase Inhibitor p21; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D019938:Cyclin D1; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D055372:AMP-Activated Protein Kinases; C003466:thymoquinone