Immunostimulation of rat primary astrocytes decreases intracellular ATP level.
In this study we investigated the effect of immunostimulation on intracellular ATP level in rat glial cells. Rat primary astrocytes or C6 glioma cells were treated for 48 h with IFN-gamma, LPS or IFN-gamma plus LPS. These treatments increased NO production from the cells and a synergistic increase in NO production was observed with IFN-gamma plus LPS. Intracellular ATP level was decreased to about half the control level at the highest concentration of IFN-gamma (100 U/ml) plus LPS (1 microg/ml) without affecting cell viability. The level of intracellular ATP was inversely correlated with the extent of NO production from the glial cells. The increase in NO production is at least 6 h ahead of the initiation of ATP depletion, and NOS inhibitor N(G)-nitro-L-arginine (NNA) or Nomega-nitro-L-arginine methyl ester (L-NAME) inhibited NO production and ATP depletion. Exogenous addition of peroxynitrite generator 3-morpholinosydnonimine (SIN-1) and to a lesser extent NO generator S-nitroso-N-acetylpenicillamine (SNAP) depleted intracellular ATP level in a dose-dependent manner. The results from the present study imply that immunostimulation of rat glial cells decreases the intracellular ATP level without affecting cell viability. Considering the role of astrocytes as an essential regulator of the extracellular environment in the brain, the immunostimulation-induced decrease in intracellular ATP level may participate in the pathogenesis of various neurological diseases.
Shin
C Y
CY
Department of Pharmacology, College of Pharmacy, Seoul National University, San 56-1, Shillim-Dong, Kwanak-Gu, 151-742, Seoul, South Korea.
Choi
J W
JW
Ryu
J R
JR
Ryu
J H
JH
Kim
W
W
Kim
H
H
Ko
K H
KH
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018836:Inflammation Mediators / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D007424:Intracellular Fluid / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009566:Nitrates; D019335:Nitroarginine; C039642:peroxynitric acid; D009569:Nitric Oxide; C002385:linsidomine; D026423:S-Nitroso-N-Acetylpenicillamine; D007371:Interferon-gamma; D000255:Adenosine Triphosphate; D008981:Molsidomine; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D010396:Penicillamine; D019331:NG-Nitroarginine Methyl Ester