Abstract: Carnosine (β-alanyl-L-histidine) and related peptides such as
homocarnosine (γ-amino-butyryl-histidine), balenine
β-alanyl-L-3-methylhistidine) and anserine
β-alanyl-L-1-methylhistidine) are histidine-containing dipeptides (HD)
particularly abundant in excitable tissues such as nervous system and skeletal
muscle. Although their biochemical role is still unknown, several evidences
indicate that these endogenous compounds act as quenchers of reactive and
cytotoxic carbonyl species. In this presentation we will review the structural
evidences and ex vivo data supporting this hypothesis. We first elucidated the
reaction mechanism of carnosine as quencher of α, β-unsaturated
aldehydes such as 4-hydroxy-trans-2,3-nonenal (HNE) and acrolein (ACR) and then
demonstrated the efficacy of carnosine and related peptides as detoxifying
agents of HNE in spontaneously oxidized rat skeletal muscle, by detecting the
corresponding HNE-Michael adducts in the crude biological matrix by liquid
chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS).
Finally, we set-up and validated a sensitive, selective and specific
LC-ESI-MS/MS method for the determination of HD and of the corresponding
HNE-Michael adducts to monitor their profile in physiological (aging) and
pathological conditions (diabetes, atherosclerosis) characterized by a
carbonyl-mediated degenerative overload. The results obtained, beside to give a
contribution to the understanding of the biochemical role of
histidine-dipeptides, provide a strong rational to the design of novel
derivatives, active as exogenous agents able to detoxify carbonyl
compounds.
