Selenoprotein P Regulates PCB-Induced Oxidative Stress and Toxicity in Human Keratinocytes

Strategic Insights -

Research conducted by W. Xiao and colleagues at the University of Iowa has demonstrated that selenoprotein P (SEPP1) plays a crucial role in regulating oxidative stress and toxicity induced by polychlorinated biphenyls (PCBs) in human keratinocytes. The study, published in Free Radical Biology & Medicine, found that SEPP1 downregulation was significantly associated with an increase in oxidative stress and toxicity in HaCaT human skin keratinocytes treated with 1-(4-Chlorophenyl)-benzo-2,5-quinone (4-ClBQ), a metabolite of PCB3.

Key Takeaways:

  • SEPP1 downregulation was significantly associated with an 8-to 10-fold decrease in expression in 4-ClBQ-treated HaCaT human skin keratinocytes.
  • Overexpression of Mn-superoxide dismutase or catalase or treatment with N-acetyl-l-cysteine suppressed 4-ClBQ-induced toxicity.
  • Sodium selenite supplementation suppressed 4-ClBQ-induced decrease in SEPP1 expression, which was associated with a significant inhibition in cell death.
  • HaCaT cells overexpressing SEPP1 were resistant to 4-ClBQ-induced oxidative stress and toxicity.
  • These results demonstrate that SEPP1 represents a previously unrecognized regulator of PCB-induced biological effects.

Statistics:

  • 92 oxidative stress-response genes were analyzed using TaqMan Array Human Antioxidant Mechanisms (Life Technologies).
  • 8-to 10-fold decrease in SEPP1 expression in 4-ClBQ-treated HaCaT human skin keratinocytes.
  • 4-ClBQ-induced toxicity was suppressed by overexpression of Mn-superoxide dismutase or catalase or treatment with N-acetyl-l-cysteine.
  • Sodium selenite supplementation suppressed 4-ClBQ-induced decrease in SEPP1 expression by 50%.

Sources:

  • Selenoprotein P regulates 1-(4-Chlorophenyl)-benzo-2,5-quinone-induced oxidative stress and toxicity in human keratinocytes. Free Radical Biology & Medicine, 2013;65():70-7. (Elsevier - www.elsevier.com; Free Radical Biology & Medicine - www.elsevier.com/wps/product/cws_home/525469)