Mark4 promotes oxidative stress and inflammation via binding to PPARγ and activating NF-κB pathway in mice adipocytes

Sci Rep. 2016 Feb 18;6:21382. doi: 10.1038/srep21382.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism*
  • Animals
  • Dietary Fats / adverse effects
  • Dietary Fats / pharmacology
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Male
  • Mice
  • Mitochondria / metabolism
  • NF-kappa B / metabolism*
  • Oxidative Stress*
  • Oxygen Consumption / drug effects
  • PPAR gamma / metabolism*
  • Protein Binding / drug effects
  • Protein Serine-Threonine Kinases / metabolism*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction*

Substances

  • Dietary Fats
  • NF-kappa B
  • PPAR gamma
  • Reactive Oxygen Species
  • MARK4 protein, mouse
  • Protein Serine-Threonine Kinases