Copper induces energy metabolic dysfunction and AMPK-mTOR pathway-mediated autophagy in kidney of broiler chickens

Ecotoxicol Environ Saf. 2020 Dec 15:206:111366. doi: 10.1016/j.ecoenv.2020.111366. Epub 2020 Sep 30.

Abstract

To explore the effects of copper (Cu) on energy metabolism and AMPK-mTOR pathway-mediated autophagy in kidney, a total of 240 one-day-old broiler chickens were randomized into four equal groups and fed on the diets with different levels of Cu (11, 110, 220, and 330 mg/kg) for 49 d. Results showed that excess Cu could induce vacuolar degeneration and increase the number of autophagosomes in kidney, and the adenosine triphosphate (ATP) level and mRNA levels of energy metabolism-related genes were decreased with the increasing dietary Cu level. Moreover, immunohistochemistry and immunofluorescence showed that the positive expressions of Beclin1 and LC3-II were mainly located in cytoplasm of renal tubular epithelial cells and increased significantly with the increasing levels of Cu. The mRNA levels of Beclin1, Atg5, LC3-I, LC3-II, Dynein and the protein levels of Beclin1, Atg5, LC3-II/LC3-I and p-AMPKα1/AMPKα1 were markedly elevated in treated groups compared with control group (11 mg/kg Cu). However, the mRNA and protein levels of p62 and p-mTOR/mTOR were significantly decreased with the increasing levels of Cu. These results suggest that impaired energy metabolism induced by Cu may lead to autophagy via AMPK-mTOR pathway in kidney of broiler chickens.

Keywords: AMPK-mTOR; Autophagy; Copper; Energy metabolism; Kidney.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Autophagosomes / drug effects
  • Autophagosomes / metabolism
  • Autophagy / drug effects*
  • Chickens
  • Copper / toxicity*
  • Dietary Exposure / adverse effects
  • Dietary Exposure / analysis
  • Energy Metabolism / drug effects*
  • Energy Metabolism / genetics
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Copper
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases