Cross-talk between autophagy and apoptosis regulates testicular injury/recovery induced by cadmium via PI3K with mTOR-independent pathway

Cell Death Dis. 2020 Jan 22;11(1):46. doi: 10.1038/s41419-020-2246-1.

Abstract

Autophagy and apoptosis are two major modes of cell death. A balanced interplay between both is vital for phagocytic clearance of apoptotic testicular cells. Here, generating a SD rats model-treated with cadmium (Cd) to mimic environmental exposure on human, we show that autophagy and apoptosis present synchronous change trends in Cd-induced testicular injury/self-recovery. Further, the cross-talk of autophagy and apoptosis is investigated in four testicular cell lines (GC-1/GC-2/TM3/TM4 cells) respectively. Results reveal that Cd-exposure for five consecutive weeks induces reproductive toxicity in male rats. After one cycle of spermatogenesis within 8 weeks without Cd, toxic effects are ameliorated significantly. In vitro, we find that PI3K inhibitor 3-MA regulates apoptosis by inhibiting autophagy with mTOR-independent pathway in Cd-treated testicular cells. Conclusively, cross-talk between autophagy and apoptosis regulates testicular injury/recovery induced by Cd via PI3K with mTOR-independent pathway.

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Aging / pathology
  • Animals
  • Apoptosis* / drug effects
  • Autophagy* / drug effects
  • Cadmium / toxicity*
  • Cell Line
  • Male
  • Models, Biological
  • Oxidative Stress / drug effects
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Protein Kinase Inhibitors / pharmacology
  • Rats, Sprague-Dawley
  • Reproduction / drug effects
  • Signal Transduction* / drug effects
  • TOR Serine-Threonine Kinases / metabolism*
  • Testis / drug effects
  • Testis / injuries*
  • Testis / pathology*
  • Testis / ultrastructure

Substances

  • Protein Kinase Inhibitors
  • Cadmium
  • 3-methyladenine
  • TOR Serine-Threonine Kinases
  • Adenine