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Carnosine protects against Abeta42-induced neurotoxicity in differentiated rat PC12 cells.
- Source :
-
Cellular and molecular neurobiology [Cell Mol Neurobiol] 2008 Feb; Vol. 28 (2), pp. 307-16. Date of Electronic Publication: 2007 Nov 20. - Publication Year :
- 2008
-
Abstract
- (1) The present study was designed to investigate whether histamine is involved in the protective effect of carnosine on Abeta42-induced impairment in differentiated PC12 cells. (2) PC12 cells were exposed to Abeta42 (5 muM) for 24 h after carnosine (5 mM) applied for 18 h. Histamine receptor antagonists (diphenhydramine, zolantidine, thioperamide, clobenpropit) or histidine decarboxylase inhibitor (alpha-fluoromethylhistidine) were added 15 min before carnosine. Cell viability, glutamate release or cell surface expression of NMDA receptor was examined. (3) Abeta42 caused a concentration-dependent reduction of viability in PC12 cells and pretreatment with carnosine ameliorated this impairment. This amelioration was reversed by the H(3) receptor antagonists thioperamide and clobenpropit, but not by either the H(1) receptor antagonist diphenhydramine or the H(2) receptor antagonist zolantidine. Further, alpha-fluoromethylhistidine, an irreversible inhibitor of histidine decarboxylase, also had no effect. In the presence of Abeta42, carnosine significantly decreased glutamate release and carnosine increased the surface expression of NMDA receptor. (4) These results indicate that the mechanism by which carnosine attenuates Abeta42-induced neurotoxicity is independent of the carnosine-histidine-histamine pathway, but may act through regulation of glutamate release and NMDA receptor trafficking.
- Subjects :
- Animals
Benzothiazoles pharmacology
Cell Differentiation
Diphenhydramine pharmacology
Drug Interactions
Glutamic Acid metabolism
Histamine H1 Antagonists pharmacology
Histamine H2 Antagonists pharmacology
Histamine H3 Antagonists pharmacology
Imidazoles pharmacology
Neurons cytology
Neurons metabolism
PC12 Cells
Phenoxypropanolamines pharmacology
Piperidines pharmacology
Rats
Receptors, N-Methyl-D-Aspartate metabolism
Thiourea analogs & derivatives
Thiourea pharmacology
Amyloid beta-Peptides toxicity
Carnosine pharmacology
Neurons drug effects
Neurotoxins toxicity
Peptide Fragments toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 0272-4340
- Volume :
- 28
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cellular and molecular neurobiology
- Publication Type :
- Academic Journal
- Accession number :
- 18027086
- Full Text :
- https://doi.org/10.1007/s10571-007-9235-0