TIGAR overexpression diminishes radiosensitivity of parotid gland fibroblast cells and inhibits IR-induced cell autophagy

Int J Clin Exp Pathol. 2015 May 1;8(5):4823-9. eCollection 2015.

Abstract

Our previous study proved that TP53-induced glycolysis and apoptosis regulator (TIGAR) abrogation is able to radiosensitize glioma cells. Whether TIGAR over-expression has radio-protective effect in human parotid gland cells is still unknown. In this study human parotid gland fibroblast Hs 917.T cells were transfected with pcDNA3.1-TIGAR, and clonogenic assay was performed to investigate the radiosensitivity of Hs 917.T cells over-expressing pcDNA3.1 or pcDNA3.1-TIGAR. Western blot was carried out to demonstrate the autophagy activity of cells being irradiated, and immunofluorescence assay was used to evaluate the DNA damage repair process of irradiated Hs 917.T cells. It was revealed that TIGAR over-expression could diminish the radiosensitivity of Hs 917.T cells, and the autophagy level induced by ionizing radiation (IR) was also decreased by TIGAR transfection. The mechanism might rely on TIGAR over-expression induced ROS scavenging and NADPH increasing. Using autophagy inhibitor, it was also elaborated that IR-induced autophagy in Hs 917.T cells was protective autophagy but not traumatic autophagy.

Keywords: TIGAR; autophagy; parotid gland cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins
  • Autophagy / genetics*
  • Cell Line
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Parotid Gland / cytology*
  • Parotid Gland / metabolism
  • Phosphoric Monoester Hydrolases
  • Radiation Tolerance / genetics*
  • Reactive Oxygen Species / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Intracellular Signaling Peptides and Proteins
  • Reactive Oxygen Species
  • Phosphoric Monoester Hydrolases
  • TIGAR protein, human