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KMID : 0578320100290030245
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Molecules and Cells
2010 Volume.29 No. 3 p.245 ~ p.250
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Suppression of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 by Cell-Permeable Superoxide Dismutase in Lipopolysaccharide-Stimulated BV-2 Microglial Cells
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Lee Ji-Ae
Song Ha-Yong
Lee Su-Jin
Seo Won-Yong
Sin Dong-Hyeon
Goh Ah-Ra
Choi Soo-Young
Park Jin-Seu
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Abstract
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Oxidative stress plays a pivotal role in uncontrolled neu-roinflammation leading to many neurological diseases including Alzheimer’s. One of the major antioxidant en-zymes known to prevent deleterious effects due to oxidative stress is Cu,Zn-superoxide dismutase (SOD). In this study, we examined the regulatory function of SOD on the LPS-induced signaling pathways leading to NF-kappaB activation, expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in BV-2 cells using cell-permeable SOD. Treatment of BV-2 cells with cell-permeable SOD led to a decrease in LPS-induced reactive oxygen species (ROS) generation and significantly inhibited protein and mRNA levels of iNOS and COX-2 up-regulated by LPS. Production of NO and PGE2 in LPS stimulated BV-2 cells was significantly abrogated by pretreatment with a cell-permeable SOD fusion protein. Furthermore, cell-permeable SOD inhibited LPS-induced NF-kappaB DNA-binding activity and activation of MAP kinases including ERK, JNK, and p38 in BV-2 cells. These data indicate that SOD has a regulatory function for LPS-induced NF-kappaB activation leading to expression of iNOS and COX-2 in BV-2 cells and suggest that cell-permeable SOD is a feasible therapeutic agent for regulation of ROS-related neurological diseases.
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KEYWORD
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COX-2, iNOS, LPS, NF-κB, ROS, superoxide dismutase
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