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Mol. Cells 2010; 29(3): 245-250

Published online March 31, 2010

https://doi.org/10.1007/s10059-010-0031-1

© The Korean Society for Molecular and Cellular Biology

Suppression of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 by Cell-Permeable Superoxide Dismutase in Lipopolysaccharide-Stimulated BV-2 Microglial Cells

Ji Ae Lee1,3, Ha Yong Song1,3, Sung Mi Ju1, Su Jin Lee1, Won Yong Seo1, Dong Hyeon Sin1, Ah Ra Goh1, Soo Young Choi1,2, and Jinseu Park1,2,*

1Department of Biomedical Science and Medical and Bio-material Research Center Hallym University, Chunchon 200-702, Korea, 2Research Institute for Bioscience and Biotechnology, College of Natural Sciences, Hallym University, Chunchon 200-702, Korea, 3These authors contributed equally to this work.

Correspondence to : *Correspondence: jinpark@hallym.ac.kr

Received: July 6, 2009; Revised: November 27, 2009; Accepted: November 27, 2009

Abstract

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.

Keywords COX-2, iNOS, LPS, NF-κB, ROS, superoxide dismutase

Article

Research Article

Mol. Cells 2010; 29(3): 245-250

Published online March 31, 2010 https://doi.org/10.1007/s10059-010-0031-1

Copyright © The Korean Society for Molecular and Cellular Biology.

Suppression of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 by Cell-Permeable Superoxide Dismutase in Lipopolysaccharide-Stimulated BV-2 Microglial Cells

Ji Ae Lee1,3, Ha Yong Song1,3, Sung Mi Ju1, Su Jin Lee1, Won Yong Seo1, Dong Hyeon Sin1, Ah Ra Goh1, Soo Young Choi1,2, and Jinseu Park1,2,*

1Department of Biomedical Science and Medical and Bio-material Research Center Hallym University, Chunchon 200-702, Korea, 2Research Institute for Bioscience and Biotechnology, College of Natural Sciences, Hallym University, Chunchon 200-702, Korea, 3These authors contributed equally to this work.

Correspondence to:*Correspondence: jinpark@hallym.ac.kr

Received: July 6, 2009; Revised: November 27, 2009; Accepted: November 27, 2009

Abstract

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.

Keywords: COX-2, iNOS, LPS, NF-κB, ROS, superoxide dismutase

Mol. Cells
Aug 31, 2022 Vol.45 No.8, pp. 513~602
COVER PICTURE
Cryo-EM structure of human porphyrin transporter ABCB6 (main figure) shows that binding of hemin (inset, magenta) in concert with two glutathione molecules (cyan) primes ABCB6 for high ATP turnover (Kim et al., pp. 575-587).

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