title: Mark4 promotes oxidative stress and inflammation via binding to PPARγ and activating NF-κB pathway in mice adipocytes.
abstract: MAP/Microtubule affinity-regulating kinase 4 (Mark4) plays an important role in the regulation of microtubule organization, adipogenesis and apoptosis. However, the role of Mark4 plays in oxidative stress and inflammation are poorly understood. In this study, we found Mark4 was induced by high fat diet (HFD) while PPARγ was elevated significantly in mice adipocytes. Further analyses revealed Mark4 impaired mitochondrial oxidative respiration and increased reactive oxygen species (ROS) production. At same time, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) were greatly reduced. By treating cells with H2O2 and vitamin E (VE), Mark4 accentuated oxidative stress along with increased mRNA level of inflammatory factor interleukin-6 (IL-6) and decreased leptin mRNA. Furthermore, we found PPARγ bind to Mark4 promoter region and inhibited Mark4 expression. We showed PPARγ interacted with Mark4 and inhibited the stimulating effect of Mark4 on oxidative stress and inflammation. Finally, we demonstrated that the IKKα/NF-κB signal pathway was involved in Mark4 induced oxidative stress and inflammation, while PTDC, a special inhibitor of NF-κB signal pathway, reduced oxidative stress and inflammation. Thus, our study indicated that Mark4 was a potential drug target for treating metabolic diseases.
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Zhenjiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Yizhe
authors.initials: Y
authors.lastname: Chen
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Luo
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Weina
authors.initials: W
authors.lastname: Cao
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Zhongjie
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Xueting
authors.initials: X
authors.lastname: Lin
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, 712100, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress; D010101:Oxygen Consumption / Q000187:drug effects; D047495:PPAR gamma / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D004041:Dietary Fats; D016328:NF-kappa B; D047495:PPAR gamma; D017382:Reactive Oxygen Species; C482979:MARK4 protein, mouse; D017346:Protein Serine-Threonine Kinases