Activated AMPK promoted the decrease of lactate production in rat Sertoli cells exposed to Zearalenone

Ecotoxicol Environ Saf. 2021 Sep 1:220:112367. doi: 10.1016/j.ecoenv.2021.112367. Epub 2021 May 27.

Abstract

Zearalenone, which is ubiquitous in grains and animal feed, is a mycotoxin that can cause serious damage to animals and humans. Sertoli cells (SCs) can be used to study ZEA male reproductive toxicity in vitro. SCs provide energy for germ cells, where AMPK regulates intracellular energy. In order to explore the regulatory effect of AMPK on ZEA-induced lactate decline, we activated AMPK by AICAR and then inhibited AMPK by Compound C with ZEA-treated SCs for 24 h to detect intracellular lactate production-related indicators. Cell viability in the presence of 20 μmol/L ZEA and either 50 μmol/L AICAR or 5 μmol/L Compound C, respectively, did not damage SCs, and could effectively either activate or inhibit AMPK. Inhibition of AMPK promoted the production of pyruvate and lactate via increased expression of the glycolysis-related genes Pgam1 and the lactate production-related proteins GLUT1, LDHA, and MCT4. Activating AMPK inhibited the production of lactate and pyruvate by suppressing the expression of glycolysis-related genes HK1, Pgam1, and Gpi1 and that of lactate production-related proteins LDHA and MCT4. Zearalenone destroys the energy balance in SCs, activates P-AMPK, which inhibit the production of lactate and pyruvate in SCs. This also leads to the decrease of energy supply of SCs to spermatogenic cells, damages to reproductive system.

Keywords: AMPK; Pyruvate; Sertoli cells; Zearalenone; lactate.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Energy Metabolism / drug effects
  • Estrogens, Non-Steroidal / toxicity*
  • Glycolysis / drug effects
  • Glycolysis / genetics
  • Lactic Acid / metabolism*
  • Male
  • Pyruvic Acid / metabolism
  • Rats
  • Sertoli Cells / drug effects*
  • Sertoli Cells / metabolism
  • Zearalenone / toxicity*

Substances

  • Estrogens, Non-Steroidal
  • Lactic Acid
  • Zearalenone
  • Pyruvic Acid
  • AMP-Activated Protein Kinases