The role of MAPK and FAS death receptor pathways in testicular germ cell apoptosis induced by lead

Acta Biochim Biophys Sin (Shanghai). 2009 Sep;41(9):800-7. doi: 10.1093/abbs/gmp069.

Abstract

The aim of the present study is to investigate gene expression involved in the signal pathway of MAPK and death signal receptor pathway of FAS in lead-induced apoptosis of testicular germ cells. First, cell viabilities were determined by MTT assay. Second, using single cell gel-electrophoresis test (comet assay) and TUNEL staining technique, apoptotic rate and cell apoptosis localization of testicular germ cells were measured in mice treated with 0.15%, 0.3%, and 0.6% lead, respectively. Third, the immunolocalization of K-ras, c-fos, Fas, and active caspase-3 proteins was determined by immunohistochemistry. Finally, changes in the translational levels of K-ras, c-fos, Fas, and active caspase-3 were further detected by western blot analysis. Our results showed that lead could significantly induce testicular germ cell apoptosis in a dose-dependent manner (P<0.01). The mechanisms were closely related to the increased expressions of K-ras, c-fos, Fas, and active caspase-3 in apoptotic germ cells. In conclusion, K-ras/c-fos and Fas/caspase-3 death signaling receptor pathways were involved in the lead-induced apoptosis of the testicular germ cells in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Fas-Associated Death Domain Protein / metabolism*
  • Gene Expression
  • Lead / toxicity*
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology*
  • Male
  • Mice
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Spermatozoa / drug effects
  • Spermatozoa / physiology*

Substances

  • Fas-Associated Death Domain Protein
  • Lead
  • Mitogen-Activated Protein Kinase Kinases