title: Carnosine protects neurons against oxidative stress and modulates the time profile of MAPK cascade signaling.
abstract: Carnosine is a known protector of neuronal cells against oxidative injury which prevents both apoptotic and necrotic cellular death. It was shown earlier that carnosine serves as an intracellular buffer of free radicals. Using the model of ligand-dependent oxidative stress in neurons, we have shown that homocysteine (HC) initiates long-term activation of extracellular signal regulated kinase, isoforms 1 and 2 (ERK 1/2) and Jun N-terminal kinase (JNK) which corresponds to exitotoxic effect resulting in cellular death. L-carnosine (β-alanyl-L-histidine) protects neurons from both excitotoxic effect of homocysteine and cellular death. Its analogs, β-alanyl-D-histidine (D-carnosine) and L-histidyl-β-alanine, restricted accumulation of free radicals and delayed activation of ERK1/2 and JNK in neuronal cells, but did not promote neuronal viability.
authors.affiliation: Department of Biochemistry, School of Biology, Room 141, M.V. Lomonosov Moscow State University, Lenin's Hills, Bldg 1/12, 119992, Moscow, Russia.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Kulebyakin
authors.forename: Larisa
authors.initials: L
authors.lastname: Karpova
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Lakonsteva
authors.forename: Mikhail
authors.initials: M
authors.lastname: Krasavin
authors.forename: Alexander
authors.initials: A
authors.lastname: Boldyrev
mesh_terms: D000818:Animals; D002336:Carnosine / Q000494:pharmacology*; D002470:Cell Survival; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006710:Homocysteine / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D006710:Homocysteine; D002336:Carnosine; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases