Toxic effects of beta-amyloid(25-35) on immortalised rat brain endothelial cell: protection by carnosine, homocarnosine and beta-alanine.
The effect of a truncated form of the neurotoxin beta-amyloid peptide (A beta25-35) on rat brain vascular endothelial cells (RBE4 cells) was studied in cell culture. Toxic effects of the peptide were seen at 200 microg/ml A beta using a mitochondrial dehydrogenase activity (MTT) reduction assay, lactate dehydrogenase release and glucose consumption. Cell damage could be prevented completely at 200 microg/ml A beta and partially at 300 microg/ml A beta, by the dipeptide carnosine. Carnosine is a naturally occurring dipeptide found at high levels in brain tissue and innervated muscle of mammals including humans. Agents which share properties similar to carnosine, such as beta-alanine, homocarnosine, the anti-glycating agent aminoguanidine, and the antioxidant superoxide dismutase (SOD), also partially rescued cells, although not as effectively as carnosine. We postulate that the mechanism of carnosine protection lies in its anti-glycating and antioxidant activities, both of which are implicated in neuronal and endothelial cell damage during Alzheimer's disease. Carnosine may therefore be a useful therapeutic agent.
Preston
J E
JE
Institute of Gerontology, King's College London, UK. j.preston@kcl.ac.uk
Hipkiss
A R
AR
Himsworth
D T
DT
Romero
I A
IA
Abbott
J N
JN
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002336:Carnosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002461:Cell Line, Transformed; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D013482:Superoxide Dismutase / Q000494:pharmacology; D015091:beta-Alanine / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D006146:Guanidines; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D015091:beta-Alanine; C005038:homocarnosine; D002336:Carnosine; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; C004479:pimagedine