First isolated and characterized in 1900 by Gulewitsch, carnosine (beta-alanyl-L-hystidine) is a dipeptide commonly present in mammalian tissue, and in particular in skeletal muscle cells; it is responsible for a variety of activities related to the detoxification of the body from free radical species and the by-products of membrane lipids peroxidation, but recent studies have shown that this small molecule also has membrane-protecting activity, proton buffering capacity, formation of complexes with transition metals, and regulation of macrophage function. It has been proposed that carnosine could act as a natural scavenger of dangerous reactive aldehydes from the degradative oxidative pathway of endogenous molecules such as sugars, polyunsaturated fatty acids (PUFAs) and proteins. In particular, it has been recently demonstrated that carnosine is a potent and selective scavenger of alpha,beta-unsaturated aldehydes, typical by-products of membrane lipids peroxidation and considered second messengers of the oxidative stress, and inhibits aldehyde-induced protein-protein and DNA-protein cross-linking in neurodegenerative disorders such as Alzheimer's disease, in cardiovascular ischemic damage, in inflammatory diseases. The research for new and more potent scavengers for HNE and other alpha,beta-unsaturated aldehydes has produced a consistent variety of carnosine analogs, and the present review will resume, through the scientific literature and the international patents, the most recent developments in this field.
"L-Carnosine (β-Ala-His) is a naturally occurring histidine dipeptide, endogenously synthesized and widely found in the brain, muscle, kidney, stomach, and, in large amounts, in the skeletal muscle. This dipeptide has been proved to perform a number of biological functions, including anti-oxidant activity, ability to chelate metal ions, inhibition of protein glycosylation, anti-inflammatory and anti-senescence properties . Another aspect of the effect of L-carnosine concerns its anti-proliferative effect in human cell lines. "
[Show abstract][Hide abstract] ABSTRACT: In recent years considerable attention has been given to the use of natural substances as anticancer drugs. The natural antioxidant dipeptide L-carnosine belongs to this class of molecules because it has been proved to have a significant anticancer activity both in vitro and in vivo. Previous studies have shown that L-carnosine inhibits the proliferation of human colorectal carcinoma cells by affecting the ATP and Reactive Oxygen Species (ROS) production. In the present study we identified the Hypoxia-Inducible Factor 1α (HIF-1α) as a possible target of L-carnosine in HCT-116 cell line. HIF-1α protein is over-expressed in multiple types of human cancer and is the major cause of resistance to drugs and radiation in solid tumours. Of particular interest are experimental data supporting the concept that generation of ROS provides a redox signal for HIF-1α induction, and it is known that some antioxidants are able to suppress tumorigenesis by inhibiting HIF-1α. In the current study we found that L-carnosine reduces the HIF-1α protein level affecting its stability and decreases the HIF-1 transcriptional activity. In addition, we demonstrated that L-carnosine is involved in ubiquitin-proteasome system promoting HIF-1α degradation. Finally, we compared the antioxidant activity of L-carnosine with that of two synthetic anti-oxidant bis-diaminotriazoles (namely 1 and 2, respectively). Despite these three compounds have the same ability in reducing intracellular ROS, 1 and 2 are more potent scavengers and have no effect on HIF-1α expression and cancer cell proliferation. These findings suggest that an analysis of L-carnosine antioxidant pathway will clarify the mechanism underlying the anti-proliferative effects of this dipeptide on colon cancer cells. However, although the molecular mechanism by which L-carnosine down regulates or inhibits the HIF-1α activity has not been yet elucidated, this ability may be promising in treating hypoxia-related diseases.
PLoS ONE 05/2014; 9(5):e96755. DOI:10.1371/journal.pone.0096755 · 3.23 Impact Factor
"Up to now, the physiological and biochemical mechanisms responsible for the anti-neoplastic activity of carnosine are not clear1. Although possible mechanisms of carnosine in tumor have been extensively studied, such as influencing the chaperone activity and hypoxia inducible factor alpha signalling36, reacting with AGEs37, scavenging reactive oxygen species38, and inhibiting phosphorylation of ERK 1/2 and p38 MAP kinase1, few investigations have focused on the effects of carnosine on mTOR signaling pathway. Thus, further experiments in this study were performed in order to understand how carnosine affects the mTOR axis proteins at the molecular level. "
[Show abstract][Hide abstract] ABSTRACT: Carnosine (β-alanyl-L-histidine), described as an enigmatic peptide for its antioxidant, anti-aging and especially antiproliferation properties, has been demonstrated to play an anti-tumorigenic role in certain types of cancer. However, its function in human gastric carcinoma remains unclear. In this study, the effect of carnosine on cell proliferation and its underlying mechanisms were investigated in the cultured human gastric carcinoma cells. The mTOR signaling axis molecules were analyzed in carnosine treated cells. The results showed that treatment with carnosine led to proliferation inhibition, cell cycle arrest in the G0/G1 phase, apoptosis increase, and inhibition of mTOR signaling activation by decreasing the phosphorylation of Akt, mTOR and p70S6K, suggesting that proliferation inhibition of carnosine in human gastric carcinoma was through the inhibition of Akt/mTOR/p70S6K pathway, and carnosine would be a mimic of rapamycin.
Journal of Cancer 04/2014; 5(5):382-9. DOI:10.7150/jca.8024 · 3.27 Impact Factor
"It is also essential for DNA and RNA polymerase activity to aid cell damage that is endogenously synthesized, and widely found in the brain, muscle, kidney, stomach, and, in large amounts, in skeletal muscle (Renner et al., 2010). Carnosine has been proved to play a number of biological functions, including antioxidant activity, as a free radical scavenger, ability to chelate metal ion, anti-inflammatory and antisenescence properties (Guiottoet al.,2005). In addition, carnosine is an inhibitor of protein glycosylation and may prevent the formation of the advanced glycation end-products (AGEs) beta alanyl-L-histidine is present at surprisingly high levels (up to 20 mM) in muscle and nervous tissues in many animals. "
[Show abstract][Hide abstract] ABSTRACT: The present investigation was an attempt to study the enhancememt effect of L-carnosine (beta alanyl-l-histidine) on the influence of vaccination on healthy (non-infected) rabbits treated with Schistosoma mansoni egg antigens, cercariae antigens, and worms antigens as protective agents against infection. This study involved individual injection of three Schistosoma mansoni antigens: soluble egg antigen (SEA), cercarial antigen preparation (CAP) and soluble worm antigen preparation (SWAP), in three rabbit groups, respectively. Three other groups each received the same specific antigen in conjunction with the administration of L-carnosine, biochemical parameters including DNA, RNA, DNA/RNA ratio concentrations in addition ATPase, and acetyl cholinesterase activities were measured in liver, heart, kidney and brain in all groups. Elevation in most parameters was observed in the immunized groups. Carnosine treatment of rabbit groups immunized with SEA, CAP and SWAP in comparison to the non-carnosine-treated immunized groups resulted in amelioration the changes of DNA, RNA, ATPase and acetyl cholinesterase activities in most groups. L-carnosine has a beneficial effect in the amelioration of the changes in biochemical parameters as a result of S. mansoni antigen immunization.
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