Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Lead increases Nitric Oxide Production in Immunostimulated Glial Cells

  • Choi, Min-Sik (Department of Pharmacology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Shin, Chan-Young (Department of Pharmacology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Ryu, Jae-Ryun (Department of Pharmacology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Lee, Woo-Jong (Department of Pharmacology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Cheong, Jae-Hoon (College of Pharmacy, Sahmyook University) ;
  • Choi, Chang-Rak (Department of Neurosurgery, St.Marys Hospital, The Catholic University of Korea) ;
  • Kim, Won-Ki (Department of Pharmacology, Ewha Institute of Neuroscience, Ewha Medical School) ;
  • Ko, Kwang-Ho (Department of Pharmacology, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
  • Published : 2004.12.01
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Abstract

Lead has long been considered as a toxic environmental pollutant that severely damages the central nervous system. In various neurogenerative diseases, actrocytes become activated by proinflammatory cytokines. In the present study, we investigated whether lead (Pb$^{2+}$) affects inducible nitric oxide synthase (iNOS) expression in activated glial cells. Rat primary glial cells were stimulated with lipopolysaccharide (LPS, 1 ${\mu}$g/ml) plus IFN$_{\gamma}$(100 U/ml). Pre-treatment of Pb$^{2+}$ increased nitric oxide (NO) production in LPS/IFN$_{\gamma}$-stimulated glial cells. Lead itself, however, suppressed the basal production of NO in control glial cells. Addition of the iNOS inhibitors L-NAME (1 mM) and L-NNA (800 ${\mu}$M) prevented the Pb$^{2+}$-induced increase in NO production. Western blot analysis showed that pre-treatment of Pb$^{2+}$ augmented LPS/IFN$_{\gamma}$-induced increase in iNOS immunoreactivity, which was well correlated with the increased NO production. In addition, pre-treatment of Pb$^{2+}$ synergistically increased the iNOS mRNA expression induced by LPS and IFN${\gamma}$. The present results indicate that lead intoxication adversely affect brain function by potentiating iNOS expression and NO production in activated glial cells observed in various neurodegenerative diseases.

Keywords

References

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