Glucose deprivation decreases nitric oxide production via NADPH depletion in immunostimulated rat primary astrocytes.
We have previously reported that the production of nitric oxide (NO) in immunostimulated astrocytes was markedly decreased under glucose-deprived conditions. The present study was undertaken to find the contributing factor(s) for the decreased NO production in glucose-deprived immunostimulated astrocytes. NO production in rat primary astrocytes was stimulated for 24-48 h by cotreatment with lipopolysaccharides (1 microg/ml) and interferon-gamma (100 U/ml). Decreased NO production in immunostimulated astrocytes by glucose deprivation was mimicked by the glycolytic inhibitor 2-deoxyglucose and reversed by addition of pyruvate and lactate. Glucose deprivation did not alter the expression of inducible nitric oxide synthase (iNOS) in immunostimulated astrocytes. Addition of beta-NADPH, but not tetrahydrobiopterine, both of which are essential cofactors for NOS function, completely restored the NO production that was decreased in glucose-deprived immunostimulated astrocytes. Glucose deprivation and immunostimulation synergistically reduced intracellular NADPH level in astrocytes. The results indicate that glucose deprivation decreases NO production in immunostimulated astrocytes by depleting intracellular NADPH, a cofactor of iNOS.
Shin
Chan Young
CY
Department of Pharmacology, College of Pharmacy, Seoul National University, Seoul, South Korea.
Choi
Ji Woong
JW
Ryu
Jae Ryun
JR
Ko
Kwang Ho
KH
Choi
Jung-Jin
JJ
Kim
Hyun-Soo
HS
Kim
Hee-Sun
HS
Lee
Jae-Chul
JC
Lee
Sun Jung
SJ
Kim
Hyoung Chun
HC
Kim
Won-Ki
WK
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D003847:Deoxyglucose / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology*; D005947:Glucose / Q000172:deficiency*; D005978:Glutathione / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D019344:Lactic Acid / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009249:NADP / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D019636:Neurodegenerative Diseases / Q000201:enzymology / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000276:immunology; D019001:Nitric Oxide Synthase / Q000276:immunology / Q000378:metabolism*; D019289:Pyruvic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000276:Adjuvants, Immunologic; D008070:Lipopolysaccharides; D001708:Biopterins; D009569:Nitric Oxide; D019344:Lactic Acid; D009249:NADP; D007371:Interferon-gamma; D019289:Pyruvic Acid; D003847:Deoxyglucose; D019001:Nitric Oxide Synthase; C003402:sapropterin; D005978:Glutathione; D005947:Glucose