title: Cytosolic NADP(+)-dependent isocitrate dehydrogenase protects macrophages from LPS-induced nitric oxide and reactive oxygen species.
abstract: Macrophages activated by microbial lipopolysaccharides (LPS) produce bursts of nitric oxide and reactive oxygen species (ROS). Redox protection systems are essential for the survival of the macrophages since the nitric oxide and ROS can be toxic to them as well as to pathogens. Using suppression subtractive hybridization (SSH) we found that cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) is strongly upregulated by nitric oxide in macrophages. The levels of IDPc mRNA and of the corresponding enzymatic activity were markedly increased by treatment of RAW264.7 cells or peritoneal macrophages with LPS or SNAP (a nitric oxide donor). Over-expression of IDPc reduced intracellular peroxide levels and enhanced the survival of H2O2- and SNAP-treated RAW264.7 macrophages. IDPc is known to generate NADPH, a cellular reducing agent, via oxidative decarboxylation of isocitrate. The expression of enzymes implicated in redox protection, superoxide dismutase (SOD) and catalase, was relatively unaffected by LPS and SNAP. We propose that the induction of IDPc is one of the main self-protection mechanisms of macrophages against LPS-induced oxidative stress.
authors.affiliation: Department of Biology, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Oky
authors.initials: O
authors.lastname: Maeng
authors.forename: Yong Chan
authors.initials: YC
authors.lastname: Kim
authors.forename: Han-Jae
authors.initials: HJ
authors.lastname: Shin
authors.forename: Jie-Oh
authors.initials: JO
authors.lastname: Lee
authors.forename: Tae-Lin
authors.initials: TL
authors.lastname: Huh
authors.forename: Kwang-il
authors.initials: KI
authors.lastname: Kang
authors.forename: Young Sang
authors.initials: YS
authors.lastname: Kim
authors.forename: Sang-Gi
authors.initials: SG
authors.lastname: Paik
authors.forename: Hayyoung
authors.initials: H
authors.lastname: Lee
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D007521:Isocitrate Dehydrogenase / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology*
chemical_list: D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D007521:Isocitrate Dehydrogenase; C039355:isocitrate dehydrogenase (NADP+)