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The journal of applied pharmacology : the official journal of the Korean Society of Applied Pharmacology v.12 no.4, 2004년, pp.209 - 214  
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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  );
  • 초록

    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.

  • 주제어

    Lead ( .   primary glial cells .   lipopolysaccharide .   nitric oxide .   iNOS.  

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 저자의 다른 논문

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    2. 2005 "Adenosine and Purine Nucleosides Prevent the Disruption of Mitochondrial Transmembrane Potential by Peroxynitrite in Rat Primary Astrocytes" Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea 28 (7): 810~815    
  • Ryu, Jae-Ryun (4)

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