ROS-mediated apoptosis of HAPI microglia through p53 signaling following PFOS exposure

Environ Toxicol Pharmacol. 2016 Sep:46:9-16. doi: 10.1016/j.etap.2016.06.025. Epub 2016 Jun 27.

Abstract

Perfluorooctane sulfonate (PFOS), the most extensively studied member of perfluoroalkyl and polyfluoroalkyl substances (PFASs), has been thought to be toxic to the central nervous system (CNS) of mammals. However, the neurotoxic effects of PFOS remain largely unknown. In this study, the effect of PFOS on microglial apoptosis was examined. The results showed that PFOS could significantly reduce the cell viability and mediate cell apoptosis in HAPI microglia, which was closely accompanied with ROS production and p53 overexpression. Moreover, p53 interference significantly ameliorated PFOS-triggered cytotoxic effects in HAPI microglia, including the downregulation of cleaved PARP and cleaved caspase 3. Interestingly, NAC, a ROS inhibitor, inhibited p53 expression, and decreased the apoptosis of HAPI microglia. Taken together, these findings suggest that upregulated production of ROS plays a vital role in PFOS-mediated apoptosis in HAPI microglia via the modulation of p53 signaling.

Keywords: Microglia; PFOS; ROS; apoptosis; p53.

MeSH terms

  • Alkanesulfonic Acids / toxicity*
  • Animals
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Environmental Pollutants / toxicity
  • Enzyme Activation / drug effects
  • Fluorocarbons / toxicity*
  • Microglia / drug effects*
  • Microglia / metabolism
  • Microglia / pathology
  • Poly(ADP-ribose) Polymerases / metabolism
  • Rats
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / drug effects
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Alkanesulfonic Acids
  • Environmental Pollutants
  • Fluorocarbons
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53
  • perfluorooctane sulfonic acid
  • Poly(ADP-ribose) Polymerases
  • Caspase 3