Carnosine interaction with nitric oxide and astroglial cell protection.
The neuropeptide carnosine (beta-amyloid peptide aggregation has been demonstrated. Carnosine protection against peroxynitrite damage is particularly relevant, but until now there has been no evidence of any direct interaction with nitric oxide. In this study we examined the protection that carnosine provides against nitric oxide (NO)-induced cell death in primary rat astroglial cell cultures treated with lipopolysaccharide (LPS) and interferon gamma (INFgamma), a well-known neurotoxic proinflammatory condition. A correlation was found between cell protection and NO free-radical scavenging activity of carnosine. Moreover, by competitive spectrophotometric measurement and electrospray mass spectrometry analysis in cell-free experiments, we demonstrated a direct interaction of the dipeptide with NO. A comparison of carnosine with its homologues or derivatives (homocarnosine and carcinine) as well as with its amino acid constituents (L-histidine and beta-alanine) highlighted that only histidine showed significant scavenging activity. Therefore, carnosine shows direct NO-trapping ability and may be a valuable multifunctional molecule in the treatment of neurodegenerative disorders.
Nicoletti
Vincenzo Giuseppe
VG
Dipartimento di Scienze Chimiche, Università degli Studi di Catania, Catania, Italy. nicovigi@unict.it
Santoro
Anna Maria
AM
Grasso
Giulia
G
Vagliasindi
Laura Irene
LI
Giuffrida
Maria Laura
ML
Cuppari
Christian
C
Purrello
Vittoria Spina
VS
Stella
Anna Maria Giuffrida
AM
Rizzarelli
Enrico
E
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002336:Carnosine / Q000008:administration & dosage / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology*; D006639:Histidine / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar
D004338:Drug Combinations; D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D009498:Neurotoxins; D009569:Nitric Oxide; D006639:Histidine; D007371:Interferon-gamma; D002336:Carnosine