Critical role for the protons in FRTL-5 thyroid cells: nuclear sphingomyelinase induced-damage

Int J Mol Sci. 2014 Jun 27;15(7):11555-65. doi: 10.3390/ijms150711555.

Abstract

Proliferating thyroid cells are more sensitive to UV-C radiations than quiescent cells. The effect is mediated by nuclear phosphatidylcholine and sphingomyelin metabolism. It was demonstrated that proton beams arrest cell growth and stimulate apoptosis but until now there have been no indications in the literature about their possible mechanism of action. Here we studied the effect of protons on FRTL-5 cells in culture. We showed that proton beams stimulate slightly nuclear neutral sphingomyelinase activity and inhibit nuclear sphingomyelin-synthase activity in quiescent cells whereas stimulate strongly nuclear neutral sphingomyelinase activity and do not change nuclear sphingomyelin-synthase activity in proliferating cells. The study of neutral sphingomyelinase/sphingomyelin-synthase ratio, a marker of functional state of the cells, indicated that proton beams induce FRTL-5 cells in a proapoptotic state if the cells are quiescent and in an initial apoptotic state if the cells are proliferating. The changes of cell life are accompanied by a decrease of nuclear sphingomyelin and increase of bax protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line
  • Epithelial Cells / metabolism
  • Epithelial Cells / radiation effects
  • Protons*
  • Rats
  • Sphingomyelin Phosphodiesterase / metabolism*
  • Thyroid Gland / cytology
  • Transferases (Other Substituted Phosphate Groups) / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Protons
  • bcl-2-Associated X Protein
  • Transferases (Other Substituted Phosphate Groups)
  • phosphatidylcholine-ceramide phosphocholine transferase
  • Sphingomyelin Phosphodiesterase