title: Effects of malonate C60 derivatives on activated microglia.
abstract: Activated microglia in acute and chronic neurodegenerative disease of the central nervous system (CNS) can produce large amounts of free radicals, such as reactive oxygen species (ROS), which subsequently contribute to neuropathogenesis. Thus, it is believed that the induction of microglial deactivation can reduce neuronal injury. Buckminsterfullerene (C60) derivatives that possess free radical scavenging properties have been demonstrated to prevent neuronal cell death caused by excitotoxic insult. In this study, we investigated the biological role of two malonic acid C60 derivatives referred as trans-2 and trans-3 on microglia in the presence of the endotoxin lipopolysaccharide (LPS). Treatment of LPS-activated microglia with trans-2 and trans-3 induced a significant degree of transformation of amoeboid microglia to the ramified phenotype. To understand the mechanism underlying this C60 mediated microglial morphological transformation, we examined the production of proinflammatory cytokines, interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), as well as the final NO products (nitrate and nitrite) in the microglial culture supernatant. Although inducible nitric oxide (iNOS) mRNA and protein expression in LPS-activated microglia were slightly decreased by trans-2 and trans-3, levels of nitrate and nitrite were unaffected. Paradoxically, trans-2 and trans-3 were found to increase the release of IL-1beta in the activated microglial culture. However, trans-2 and trans-3 improved the activity of the antioxidant enzyme, superoxide dismutase (SOD) in LPS-treated microglia. Therefore, our results suggest that the C60 derivatives might increase microglial SOD enzymatic activity which causes microglial morphological transformation from the activated amoeboid phenotype to the resting ramified form.
authors.affiliation: Department of Biology, National Cheng Kung University, Tainan City, Taiwan. stzeng@mail.ncku.edu
authors.forename: Shun-Fen
authors.initials: SF
authors.lastname: Tzeng
authors.forename: Jia-Ling
authors.initials: JL
authors.lastname: Lee
authors.forename: Jon-Sun
authors.initials: JS
authors.lastname: Kuo
authors.forename: Chung-Shi
authors.initials: CS
authors.lastname: Yang
authors.forename: Periyagamy
authors.initials: P
authors.lastname: Murugan
authors.forename: Lin
authors.initials: L
authors.lastname: Ai Tai
authors.forename: Kuo
authors.initials: K
authors.lastname: Chu Hwang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D020536:Enzyme Activators / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008314:Malonates / Q000494:pharmacology*; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D020536:Enzyme Activators; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008314:Malonates; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C464488:m2C60 compound; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D013482:Superoxide Dismutase