The anti-apoptotic and anti-autophagic effects of EPO through PI3K/Akt/mTOR signaling pathway in MAC-T cells

Res Vet Sci. 2022 Dec:149:1-10. doi: 10.1016/j.rvsc.2022.06.005. Epub 2022 Jun 12.

Abstract

Lipopolysaccharide (LPS) is an important inflammatory and infected factor of bacterial mastitis, which treated bovine mammary epithelial cells (MAC-T) in our previous studies, as mastitis cells model in vitro. Erythropoietin (EPO) is a well-known hematopoietic hormone with antioxidative, anti-apoptotic, and anti-inflammatory roles. We hypothesized that EPO might regulate the apoptosis and autophagy to attenuate the inflammation of mastitis. Western blot, RT-PCR, transmission electron microscope analysis and Annexin V-FITC/PI were used to evaluate the regulation of EPO on apoptosis and autophagy in inflammatory MAC-T cells. These results demonstrated that EPO promoted the proliferation of MAC-T cells. Meanwhile, EPO had a better anti-inflammatory effect in MAC-T cells with LPS treatment. Certainly, EPO also showed anti-apoptotic and anti-autophagic effects. Interestingly, we found that the beneficial effect of EPO on inflammatory MAC-T cells depended on the PI3K/Akt/mTOR signaling pathway, which was involved in the regulation of apoptosis and autophagy. Generally, this study provides an insight for EPO to inhibit apoptosis and autophagy of inflammatory MAC-T cells via PI3K/Akt/mTOR signaling pathway.

Keywords: Apoptosis; Autophagy; Erythropoietin; Inflammation; MAC-T cells; PI3K/Akt/mTOR signaling.

MeSH terms

  • Animals
  • Apoptosis
  • Autophagy
  • Cattle
  • Cattle Diseases*
  • Erythropoietin* / pharmacology
  • Female
  • Lipopolysaccharides / pharmacology
  • Mastitis* / veterinary
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • T-Lymphocytes / metabolism
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Lipopolysaccharides
  • Erythropoietin
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases