Carnosine and Related Peptides: Therapeutic Potential in Age-Related Disorders

Cararo, José H.; Streck, Emílio L.; Schuck, Patrícia Fernanda; Ferreira, Gustavo da Costa

doi:10.14336/ad.2015.0616

Cited by 47 publications

(19 citation statements)

References 112 publications

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“…In most instances, the beneficial effects of Car treatment were related to its generally ascribed antioxidant activity [31], which involves a capacity to decrease both ROS and RNS in different experimental models [32, 33]. In agreement with these and other studies, our experiments with cultured murine RAW 264.7 macrophages, using ME-LIF to detect the stable fluorescent NO adduct in cell lysates [27, 34], confirmed that Car decreases NO concentration in stimulated cells in a dose-dependent manner (Fig.…”

Section: Discussionmentioning

confidence: 99%

Carnosine modulates nitric oxide in stimulated murine RAW 264.7 macrophages

et al. 2017

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Excess nitric oxide (NO) production occurs in several pathological states, including neurodegeneration, ischemia, and inflammation, and is generally accompanied by increased oxidative/nitrosative stress. Carnosine (β-alanine-histidine (β-Ala-His)) has been reported to decrease oxidative/nitrosative stress-associated cell damage by reducing the amount of NO produced. In this study, we evaluated the effect of carnosine on NO production by murine RAW 264.7 macrophages stimulated with lipopolysaccharides + interferon-γ. Intracellular NO and intracellular and extracellular nitrite were measured by microchip electrophoresis with laser-induced fluorescence and by the Griess assay, respectively. Results showed that carnosine causes an apparent suppression of total NO production by stimulated macrophages accompanied by an unexpected simultaneous drastic increase in its intracellular low toxicity end product, nitrite, with no inhibition of inducible nitric oxide synthase (iNOS). ESI-MS and NMR spectroscopy in a cell-free system showed the formation of multiple adducts (at different ratios) of carnosine-NO and carnosine-nitrite, involving both constituent amino acids (β-Ala and His) of carnosine, thus providing a possible mechanism for the changes in free NO and nitrite in the presence of carnosine. In stimulated macrophages, the addition of carnosine was also characterized by changes in the expression of macrophage activation markers and a decrease in the release of IL-6, suggesting that carnosine might alter M1/M2 macrophage ratio. These results provide evidence for previously unknown properties of carnosine that modulate the NO/nitrite ratio of stimulated macrophages. This modulation is also accompanied by changes in the release of pro-inflammatory molecules, and does not involve the inhibition of iNOS activity.

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Section: Discussionmentioning

confidence: 99%

Carnosine modulates nitric oxide in stimulated murine RAW 264.7 macrophages

et al. 2017

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“…Although the effect of each SNP and dietary factor is small, the combined effect of the genetic and dietary factor is rather strong. CNDP1 and CNDP2 are dipeptidases that are related to the metabolism of carnosine or GSH, respectively [10,11,14,15], which are the most abundant naturally occurring endogenous dipeptide and tripeptide with antioxidant and free radical scavenger properties, respectively [11,12,13,16]. In addition, CNDP2 seems to be a Cys-Gly peptidase of the γ-glutamyl cycle.…”

Section: Discussionmentioning

confidence: 99%

“…Naturally occurring endogenous dipeptides containing histidine, such as carnosine, anserine, and homocarnosine, have antioxidant and free radical scavenging properties [10,11,12]. Carnosine is the most abundant dipeptide and plays an important role in humans [10,11,12,13].…”

Section: Introductionmentioning

confidence: 99%

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The Combined Effects of Genetic Variation in the CNDP1 and CNDP2 Genes and Dietary Carbohydrate and Carotene Intake on Obesity Risk

Yamakawa‐Kobayashi

Otagi²,

Ohhara³

et al. 2017

Lifestyle Genomics

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Background/Aims: It is possible that carnosinase (CNDP1) and cellular nonspecific dipeptidase (CNDP2) have important roles in protecting cells and tissues against the damage of oxidative stress. Oxidative stress and subsequent inflammation are key factors in the development of common chronic metabolic diseases, such as obesity. We aimed to investigate the combined effects of genetic variations in CNDP1 and CNDP2 and dietary carbohydrate and carotene intake on obesity risk. Methods: A total of 1,059 Japanese men were randomly selected from participants who visited a medical center for routine medical checkups. We analyzed the relationships between the genotypes of 4 single-nucleotide polymorphisms (SNPs) (rs12605520, rs7244647, rs4891558, and rs17089368) in the CNDP1/CNDP2 locus and body mass index or prevalence of obesity/overweight taking into account dietary carbohydrate and carotene intake. Results: We found that 2 SNPs (rs7244647 in CNDP1 and rs4891558 in CNDP2) were associated with obesity risk. In addition, these associations were observed only in the group with high carbohydrate and low carotene intake but not in the group with low carbohydrate and high carotene intake. Conclusions: Our findings indicate that the combination of genetic variations in CNDP1 and CNDP2 and dietary carbohydrate/carotene intake modulate obesity risk.

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“…Admittedly, the topic is not without controversy [ 16 ], probably confounded by geographical (exposure to sunlight) and other factors. Furthermore, it has been suggested that carnosine is an anti-aging substance with a beneficial effect on the cardiovascular system [ 3 , 17 , 18 ]. There is, however, evidence that vegetarians have lower rates of coronary heart disease, hypertension, etc.…”

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confidence: 99%