Selenium Antagonizes the Lead-Induced Apoptosis of Chicken Splenic Lymphocytes In Vitro by Activating the PI3K/Akt Pathway

Biol Trace Elem Res. 2018 Mar;182(1):119-129. doi: 10.1007/s12011-017-1088-x. Epub 2017 Jul 5.

Abstract

Lead (Pb) pollution has become one of the most serious global ecological problems. In animals, Pb ingestion induces apoptosis in many tissues. However, the mechanisms by which Pb induces apoptosis in chicken splenic lymphocytes in vitro via the PI3K/Akt pathway and the antagonistic effect of selenium (Se) on Pb remain unclear. Therefore, we established the in vitro Se-Pb interaction model in chicken splenic lymphocytes and examined the frequency of apoptotic cells using acridine orange/ethidium bromide (AO/EB) staining and the TdT-mediated dUTP nick end labeling assay and detected the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT), as well as the levels of malondialdehyde (MDA) and reactive oxygen species (ROS). The expression of PI3K/Akt pathway-related genes was also examined by qRT-PCR and western blotting. MDA and ROS levels were markedly increased, whereas the activities of GPx, SOD, and CAT were significantly decreased; the levels of the PI3K, Akt, and Bcl-2 messenger RNAs (mRNAs) and proteins were decreased; and the levels of the p53, Bax, cytochrome c (Cyt-c), caspase 3, and caspase 9 mRNAs and proteins were increased in the Pb group. In addition, the frequency of apoptotic cells was also significantly increased by the Pb treatment. However, Se supplementation during Pb exposure observably attenuated Pb-induced apoptosis; increased the levels of the PI3K, Akt, and Bcl-2 mRNAs and proteins; and decrease the levels of the p53, Bax, Cyt-c, caspase 3, and caspase 9 mRNAs and proteins in the chicken spleen. In conclusion, Pb exposure causes oxidative stress, inhibits the PI3K/Akt pathway, and subsequently induces apoptosis in chicken splenic lymphocytes in vitro, and these effects are partially attenuated by Se supplementation. To the best of our knowledge, this study is the first to reveal the antagonistic effect of Se on Pb-induced apoptosis of chicken splenic lymphocytes in vitro via the activation of the PI3K/Akt pathway.

Keywords: Chicken; Lead; PI3K/Akt pathway; Selenium; Splenic lymphocytes.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Avian Proteins / genetics
  • Avian Proteins / metabolism
  • Catalase / metabolism
  • Cells, Cultured
  • Chickens
  • Drug Antagonism
  • Gene Expression / drug effects
  • Glutathione Peroxidase / metabolism
  • Lead / pharmacology*
  • Lymphocytes / cytology
  • Lymphocytes / drug effects*
  • Lymphocytes / metabolism
  • Malondialdehyde / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Reactive Oxygen Species / metabolism
  • Selenium / pharmacology*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Spleen / cytology
  • Superoxide Dismutase / metabolism

Substances

  • Avian Proteins
  • Reactive Oxygen Species
  • Lead
  • Malondialdehyde
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Selenium