Carnosine
Use of carnosine as a natural anti-senescence drug for human beings.
Wang AM, Ma C, Xie ZH, Shen F Department of Biochemistry, Harbin Medical University, Harbin, 150086, PR China. Wangam@ems.hrbmu.edu.cn.
Biochemistry (Mosc) 2000 Jul;65(7):869-71
Carnosine is an endogenous free-radical scavenger. The latest research has indicated that apart from the function of protecting cells from oxidation-induced stress damage, carnosine appears to be able to extend the lifespan of cultured cells, rejuvenate senescent cells, inhibit the toxic effects of amyloid peptide (Abeta), malondialdehyde, and hypochlorite to cells, inhibit glycosylation of proteins and protein-DNA and protein-protein cross-linking, and maintain cellular homeostasis. Also, carnosine seems to delay the impairment of eyesight with aging, effectively preventing and treating senile cataract and other age-related diseases. Therefore, carnosine may be applied to human being as a drug against aging.
A role for carnosine in cellular maintenance.
Holliday R, McFarland GA CSIRO Division of Molecular Science, Sydney, N. S. W. 1670, Australia. gail.mcfarland@molsci.csiro.au.
Biochemistry (Mosc) 2000 Jul;65(7):843-8
The dipeptide L-carnosine has beneficial effects on cultured human fibroblasts. Physiological concentrations in standard media prolong their in vitro lifespan and strongly reduce the normal features of senescence. Late passage cells in normal medium are rejuvenated when transferred to medium containing carnosine, and become senescent when carnosine is removed. In the absence of pyruvate, carnosine is cytotoxic to neoplastic and transformed human and rodent cells. None of these effects are seen with its optical isomer, D-carnosine.
Carnosine reacts with a glycated protein.
Brownson C, Hipkiss AR Division of Biomolecular Science, GKT School of Biomedical Sciences, King's College London, Guy's Campus, London Bridge, London, UK.
Free Radic Biol Med 2000 May 15;28(10):1564-70
Oxidation and glycation induce formation of carbonyl (CO) groups in proteins, a characteristic of cellular aging. The dipeptide carnosine (beta-alanyl-L-histidine) is often found in long-lived mammalian tissues at relatively high concentrations (up to 20 mM). Previous studies show that carnosine reacts with low-molecular-weight aldehydes and ketones. We examine here the ability of carnosine to react with ovalbumin CO groups generated by treatment of the protein with methylglyoxal (MG). Incubation of MG-treated protein with carnosine accelerated a slow decline in CO groups as measured by dinitrophenylhydrazine reactivity. Incubation of [(14)C]-carnosine with MG-treated ovalbumin resulted in a radiolabeled precipitate on addition of trichloroacetic acid (TCA); this was not observed with control, untreated protein. The presence of lysine or N-(alpha)-acetylglycyl-lysine methyl ester caused a decrease in the TCA-precipitable radiolabel. Carnosine also inhibited cross-linking of the MG-treated ovalbumin to lysine and normal, untreated alpha-crystallin. We conclude that carnosine can react with protein CO groups (termed "carnosinylation") and thereby modulate their deleterious interaction with other polypeptides. It is proposed that, should similar reactions occur intracellularly, then carnosine's known "anti-aging" actions might, at least partially, be explained by the dipeptide facilitating the inactivation/removal of deleterious proteins bearing carbonyl groups.
A possible new role for the anti-ageing peptide carnosine.
Hipkiss AR, Brownson C Biomolecular Sciences Division, GKT School of Biomedical Sciences, King's College London, UK. alan.hipkiss@kcl.ac.uk
Cell Mol Life Sci 2000 May;57(5):747-53
The naturally occurring dipeptide carnosine (beta-alanyl-L-histidine) is found in surprisingly large amounts in long-lived tissues and can delay ageing in cultured human fibroblasts. Carnosine has been regarded largely as an anti-oxidant and free radical scavenger. More recently, an anti-glycating potential has been discovered whereby carnosine can react with low-molecular-weight compounds that bear carbonyl groups (aldehydes and ketones). Carbonyl groups, arising mostly from the attack of reactive oxygen species and low-molecular-weight aldehydes and ketones, accumulate on proteins during ageing. Here we propose, with supporting evidence, that carnosine can react with protein carbonyl groups to produce protein-carbonyl-carnosine adducts ('carnosinylated' proteins). The various possible cellular fates of the carnosinylated proteins are discussed. These proposals may help explain anti-ageing actions of carnosine and its presence in non-mitotic cells of long-lived mammals.
[Carnosine stabilization of the normal erythrocyte membranes and in experimental diabetes]. [Article in Russian]
Korobov VN, Maurisio RB, Mukalov IO, Stvolinskii SL
Patol Fiziol Eksp Ter 2000 Apr-Jun;(2):13-5
The effect of carnosine on red blood cell membranes was studied in the in vitro and in vivo experiments. Carnosine (70-720 microM) is shown to protect healthy donors' red blood cells from acidic hemolysis increasing population of stable red blood cells and postponing time to maximal rate of hemolysis. It was demonstrated on the model of streptozotocin-induced diabetes in rats that carnosine treatment (50 mg/kg/day during 7 days, per os) prevents a decrease in the hemolytic stability of red blood cells in diabetic animals. The findings suggest usefulness of carnosine as a possible treatment of diabetes patients.
Effects of carnosine and related compounds on the stability and morphology of erythrocytes from alcoholics.
Prokopieva VD, Bohan NA, Johnson P, Abe H, Boldyrev AA Mental Health Research Institute, Medical Academy of Sciences of Russia, Tomsk, Russia.
Alcohol Alcohol 2000 Jan;35(1):44-8
The effects of carnosine and related compounds on erythrocytes from alcoholics were studied. In their presence, erythrocytes showed an increased ability to resist haemolysis and showed a more normal morphology, with carnosine and N-acetyl-carnosine being the most effective compounds. These beneficial properties of the dipeptides do not appear to be directly related to their antioxidant or buffering properties.
[Carnosine in patients with type I diabetes mellitus]. [Article in Slovak]
Gayova E, Kron I, Suchozova K, Pavlisak V, Fedurco M, Novakova B Ist Department of Internal Medicine, Medical Faculty, Safarikiensis University, Kosice, Slovakia. internal.ke@mailbox.sk
Bratisl Lek Listy 1999 Sep;100(9):500-2
Examination of carnosine in patients with diabetes mellitus type I, showed that the plasma levels of carnitine were non significantly increased compared to the levels in healthy population, while the levels in red cells were decreased Lowered levels of carnosine in red cells could point out similar deficit in other cells. Due to low levels in cells carnosine is less available for metabolic processes, like antioxidant reactions and its participation in antioxidants defense reactions is limited non-enzymatic glycosylation of proteins. Therefore it should be supplemented. (Tab. 1, Fig. 1, Ref. 15.)