Dual-specificity phosphatase 1 regulates cell cycle progression and apoptosis in cumulus cells by affecting mitochondrial function, oxidative stress, and autophagy

Am J Physiol Cell Physiol. 2019 Dec 1;317(6):C1183-C1193. doi: 10.1152/ajpcell.00012.2019. Epub 2019 Sep 18.

Abstract

Dual-specificity phosphatase 1 (DUSP1) is differentially expressed in cumulus cells of different physiological states, but its specific function and mechanism of action remain unclear. In this study, we explored the effects of DUSP1 expression inhibition on cell cycle progression, proliferation, apoptosis, and lactate and cholesterol levels in cumulus cells and examined reactive oxygen species levels, mitochondrial function, autophagy, and the expression of key cytokine genes. The results showed that inhibition of DUSP1 in cumulus cells caused abnormal cell cycle progression, increased cell proliferation, decreased apoptosis rates, increased cholesterol synthesis and lactic acid content, and increased cell expansion. The main reason for these effects was that inhibition of DUSP1 reduced ROS accumulation, increased glutathione level and mitochondrial membrane potential, and reduced autophagy levels in cells. These results indicate that DUSP1 limits the biological function of bovine cumulus cells under normal physiological conditions and will greatly contribute to further explorations of the physiological functions of cumulus cells and the interactions of the cumulus-oocyte complex.

Keywords: DUSP1; apoptosis; autophagy; cumulus cells; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Autophagy / genetics
  • Cattle
  • Cell Cycle / genetics*
  • Cell Proliferation / genetics
  • Cholesterol / metabolism
  • Cumulus Cells / cytology
  • Cumulus Cells / metabolism*
  • Dual Specificity Phosphatase 1 / antagonists & inhibitors
  • Dual Specificity Phosphatase 1 / genetics*
  • Dual Specificity Phosphatase 1 / metabolism
  • Female
  • Gene Expression Regulation
  • Glutathione / metabolism
  • Lactic Acid / metabolism
  • Membrane Potential, Mitochondrial / genetics
  • Mitochondria / physiology*
  • Oxidative Stress
  • Primary Cell Culture
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • Lactic Acid
  • Cholesterol
  • Dual Specificity Phosphatase 1
  • Glutathione