The effect of ammonium chloride on metabolism of primary neurons and neuroblastoma cells in vitro.
Hyperammonemia is a consistent finding in many metabolic disorders. The excess ammonia (NH4Cl) interferes with brain energy metabolism possibly in part by inhibiting the tricarboxylic acid (TCA) cycle. Inhibition of the TCA cycle may result in depletion of ATP in the brain cells. In this study, the acute and chronic effect of NH4Cl (7.5 mM and 15 mM) on the metabolism of isolated neurons and neuroblastoma cells was examined. These cells were treated with NH4Cl for 15 minutes and 24 hours. Morphologic and metabolic toxicity were greater in neuroblastoma cells than in primary neurons. Following 15 minutes treatment, concentration of lactate increased significantly in neuroblastoma cells but, the concentration of other metabolites did not change significantly in neuroblastoma cells and in primary neurons. Following 24 hours treatment, the glucose utilization increased in both cell types. This high utilization of glucose in neuroblastoma cells was in concert with an increase in lactate and decrease in glutamate and ATP. In primary neurons, following 24 hours treatment, the glucose utilization significantly increased, but the concentration of the other metabolites did not change significantly. Neuroblastoma cells consumed more glucose than primary neurons in absence of NH4Cl, but generated the same amount of lactate as neurons.
Haghighat
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N
Department of Cell Biology and Anatomy, Finch University of Health Sciences/The Chicago Medical School, North Chicago, Illinois 60064, USA. haghighn@finchcms.edu
McCandless
D W
DW
Geraminegad
P
P
D000255:Adenosine Triphosphate / Q000378:metabolism; D000643:Ammonium Chloride / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005333:Fetus; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000378:metabolism / Q000503:physiopathology; D022124:Hyperammonemia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D019344:Lactic Acid / Q000378:metabolism; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
D000643:Ammonium Chloride; D010725:Phosphocreatine; D019344:Lactic Acid; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D005947:Glucose