Mitogen-activated protein kinase phosphatase 1 negatively regulates MAPK signaling in mouse hypothalamus

Neurosci Lett. 2014 May 21:569:49-54. doi: 10.1016/j.neulet.2014.03.032. Epub 2014 Mar 28.

Abstract

Mitogen-activated protein kinase phosphatase 1 (MKP-1) is shown to negatively regulate MAPK signaling in various peripheral tissues as well as the central nervous system such as cortex, striatum and hippocampus. In this study, we examined whether MKP-1 regulates MAPK signaling in the mouse hypothalamus. Intraperitoneal injection of TNFα significantly increased MKP-1 mRNA expression in paraventricular and arcuate nuclei in the hypothalamus. TNFα treatment induced increases in MKP-1 expression at both mRNA and protein levels, accompanied by the inactivation of MAPK signaling in mouse hypothalamic explants. Inhibition of MKP-1 by its inhibitor or siRNA increased MAPK activity in the explants. Our data indicate that MKP-1 negatively regulates MAPK signaling in the mouse hypothalamus.

Keywords: Hypothalamus; Inflammation; MAPK; MKP-1.

MeSH terms

  • Animals
  • Dual Specificity Phosphatase 1 / antagonists & inhibitors
  • Dual Specificity Phosphatase 1 / genetics
  • Dual Specificity Phosphatase 1 / metabolism*
  • Hypothalamus / metabolism*
  • MAP Kinase Signaling System*
  • Male
  • Mice, Inbred C57BL
  • Organ Culture Techniques
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • RNA, Messenger
  • RNA, Small Interfering
  • Tumor Necrosis Factor-alpha
  • Dual Specificity Phosphatase 1
  • Dusp1 protein, mouse