Suppression of inducible nitric oxide synthase and cyclooxygenase-2 by cell-permeable superoxide dismutase in lipopolysaccharide-stimulated BV-2 microglial cells

Molecules and Cells
Ji Ae LeeJinseu Park

Abstract

Oxidative stress plays a pivotal role in uncontrolled neuro-inflammation leading to many neurological diseases including Alzheimer's. One of the major antioxidant enzymes 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 upregulated 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 f...Continue Reading

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Citations

Apr 24, 2012·Clinical and Experimental Pharmacology & Physiology·Yoko S KanekoToshiharu Nagatsu
Nov 28, 2014·Journal of Translational Medicine·Saima GulMuhammad Zia-Ul-Haq
Feb 19, 2011·Biochemical and Biophysical Research Communications·Yea-Hyun LeemSang-Ho Lee
Jun 4, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Dong-Joo KwonJinseu Park
Dec 30, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Govindhan Annamalai, Kathiresan Suresh

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