A glutamatergic mechanism for aluminum toxicity in astrocytes |
| |
Authors: | H. Ronald Zielke Marian J. Jackson J. Tyson Tildon Stephen R. Max |
| |
Affiliation: | 1. Department of Pediatrics, University of Maryland School of Medicine, 655 W. Baltimore St., 21201, Baltimore, MD 2. Medical Biotechnology Center, University of Maryland School of Medicine, 21201, Baltimore, MD 3. Department of Neurology, University of Maryland School of Medicine, 21201, Baltimore, MD 4. Department of Biological Chemistry, University of Maryland School of Medicine, 21201, Baltimore, MD 5. Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, Catonsville, MD
|
| |
Abstract: | The effect of aluminum on the metabolism of glutamate and glutamine in astrocytes was studied to provide information about a possible biochemical mechanism for aluminum neurotoxicity and its potential contribution to neurodegenerative disease. Exposure of cultured rat brain astrocytes for 3–4 d to 5–7.5 mM aluminum lactate increased glutamine synthetase activity by 100–300% and diminished glutaminase activity by 50–85%. Increased glutamine synthetase enzyme activity was accompanied by an elevated level of glutamine synthetase mRNA. Alterations in glutaminase and glutamine synthetase following aluminum exposure caused increased intracellular glutamine levels, decreased intracellular glutamate levels, and increased conversion of glutamate to glutamine and the release of the latter into the extracellular space. The results of these changes may alter the availability of neurotransmitter glutamate in vivo and may be a mechanism for the aluminum neurotoxicity observed in individuals exposed to the metal during dialysis procedures and other situations. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|