H2S mediates apoptosis in response to inflammation through PI3K/Akt/NFκB signaling pathway

Biotechnol Lett. 2020 Mar;42(3):375-387. doi: 10.1007/s10529-019-02782-3. Epub 2019 Dec 23.

Abstract

Objectives: Hydrogen sulfide (H2S) is involved in regulating cell apoptosis and proliferation. However, The effects and mechanism of H2S on the apoptosis of mammary epithelial cells that suffer from an inflammatory response remain unknown.

Results: An inflammatory cell model was used to explore whether exogenous H2S regulates lipopolysaccharides (LPS)-induced cell proliferation and apoptosis. We found that H2S affected cell viability, the inflammatory response and apoptosis in LPS-treated cells in a concentration-dependent manner. Moreover, exogenous H2S rescued LPS-induced cystathionine γ-lyase (CSE) inhibition and cystathionine β-synthase (CBS) synthesis. Interestingly, in cells undergoing inflammation-induced apoptosis, H2S activated the PI3K/Akt and NFκB signal pathways both tested concentrations. Akt appeared to be a key crosstalk molecule that played a "bridge" role.

Conclusions: H2S regulates LPS-induced inflammation and apoptosis by activating the PI3K/Akt/NFκB signaling pathway. Hence, NaHS may be clinically useful for preventing or treating mastitis.

Keywords: Apoptosis; H2S; LPS; MAC-T cells; PI3K/Akt/NFκB pathway.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cattle
  • Cell Line
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Female
  • Hydrogen Sulfide / pharmacology*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Mammary Glands, Animal / metabolism*
  • Mammary Glands, Animal / pathology
  • NF-kappa B / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects*

Substances

  • NF-kappa B
  • Proto-Oncogene Proteins c-akt
  • Hydrogen Sulfide