title: Activation-induced cell death of rat astrocytes.
abstract: Inflammatory activation of astrocytes has been implicated in various neurodegenerative diseases. The elimination of activated astrocytes by apoptosis or the deactivation may be the mechanisms for auto-regulation of activated astrocytes. To test the possibility of apoptotic elimination of activated astrocytes, we examined a potential correlation between activation state of astrocytes and their viability using C6 rat glial cells and rat primary astrocyte cultures exposed to a variety of inflammatory stimuli such as lipopolysaccharide, interferon-gamma, and tumor necrosis factor-alpha. Nitric oxide production was measured to evaluate inflammatory activation of astrocytes. We found that: (i) the activation of astrocytes by the combination of lipopolysaccharide and inflammatory cytokines, but not by either alone, led to nitric oxide production followed by apoptotic cell death; (ii) the amount of nitric oxide produced by activated astrocytes was inversely proportional to the viability of the cells; (iii) inhibition of nitric oxide synthase by N-monomethyl L-arginine blocked death of activated astrocytes; and (iv) nitric oxide donors induced apoptosis of astrocytes in a caspase-dependent manner. Taken collectively, our results suggest that activated astrocytes produce nitric oxide as an autocrine mediator of caspase-dependent apoptosis, and this type of programmed cell death of astrocytes may be the underlying mechanism for the auto-regulation of inflammatory activation of astrocytes.
authors.affiliation: Department of Herbal Pharmacology, Graduate School of East-West Medical Science, Kyung Hee University, Hoegi-dong, Tongdaemun-ku, 130-701, Seoul, South Korea. ksuk@nms.kyunghee.ac.kr
authors.forename: K
authors.initials: K
authors.lastname: Suk
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Hur
authors.forename: Y S
authors.initials: YS
authors.lastname: Kim
authors.forename: M
authors.initials: M
authors.lastname: Lee
authors.forename: S
authors.initials: S
authors.lastname: Cha
authors.forename: S
authors.initials: S
authors.lastname: Yeou Kim
authors.forename: H
authors.initials: H
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D020169:Caspases / Q000502:physiology; D002478:Cells, Cultured; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004338:Drug Combinations; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D020030:Nitric Oxide Donors; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D020169:Caspases