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2-Oxo-histidine-containing dipeptides are functional oxidation products.

ABSTRACT: Imidazole-containing dipeptides (IDPs), such as carnosine and anserine, are found exclusively in various animal tissues, especially in the skeletal muscles and nerves. IDPs have antioxidant activity because of their metal-chelating and free radical-scavenging properties. However, the underlying mechanisms that would fully explain IDP antioxidant effects remain obscure. Here, using HPLC-electrospray ionization-tandem MS analyses, we comprehensively investigated carnosine and its related small peptides in the soluble fractions of mouse tissue homogenates and ubiquitously detected 2-oxo-histidine-containing dipeptides (2-oxo-IDPs) in all examined tissues. We noted enhanced production of the 2-oxo-IDPs in the brain of a mouse model of sepsis-associated encephalopathy. Moreover, in SH-SY5Y human neuroblastoma cells stably expressing carnosine synthase, H2O2 exposure resulted in the intracellular production of 2-oxo-carnosine, which was associated with significant inhibition of the H2O2 cytotoxicity. Notably, 2-oxo-carnosine showed a better antioxidant activity than endogenous antioxidants such as GSH and ascorbate. Mechanistic studies indicated that carnosine monooxygenation is mediated through the formation of a histidyl-imidazole radical, followed by the addition of molecular oxygen. Our findings reveal that 2-oxo-IDPs are metal-catalyzed oxidation products present in vivo and provide a revised paradigm for understanding the antioxidant effects of the IDPs.

SUBMITTER: Ihara H

PROVIDER: S-EPMC6349118 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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2-Oxo-histidine-containing dipeptides are functional oxidation products.

Ihara Hideshi H Kakihana Yuki Y Yamakage Akane A Kai Kenji K Shibata Takahiro T Nishida Motohiro M Yamada Ken-Ichi KI Uchida Koji K

The Journal of biological chemistry 20181130 4

Imidazole-containing dipeptides (IDPs), such as carnosine and anserine, are found exclusively in various animal tissues, especially in the skeletal muscles and nerves. IDPs have antioxidant activity because of their metal-chelating and free radical-scavenging properties. However, the underlying mechanisms that would fully explain IDP antioxidant effects remain obscure. Here, using HPLC-electrospray ionization-tandem MS analyses, we comprehensively investigated carnosine and its related small pep ...[more]

PMID: 30504220

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Project description:IntroductionAgeing of populations globally, coupled with the obesity epidemic, has resulted in the rising prevalence of chronic diseases including diabetes, cardiovascular diseases, cancers and neurodegenerative disorders. Prevention of risk factors that contribute to these diseases is key in managing the global burden of chronic diseases. Recent studies suggest that carnosine, a dipeptide with anti-inflammatory, antioxidative and antiglycating properties may have a role in the prevention of chronic diseases; however, no previous reviews have examined the effects of carnosine and other histidine-containing peptides (HCDs) on chronic disease risk factors and outcomes. We aim to conduct a comprehensive systematic review to examine the effects of supplementation with carnosine and other HCDs on chronic disease risk factors and outcomes and to identify relevant knowledge gaps.Methods and analysisElectronic databases including Medline, Cumulative Index of Nursing and Allied Health, Embase and all Evidence-Based Medicine will be systematically searched to identify randomised controlled trials (RCTs) and systematic reviews of RCTs, comparing supplementation with carnosine and/or other HCDs versus placebo, usual care or other pharmacological or non-pharmacological interventions. One reviewer will screen titles and abstracts for eligibility according to prespecified inclusion criteria, after which two independent reviewers will perform data extraction and quality appraisal. Meta-analyses, metaregression and subgroup analyses will be conducted where appropriate.Ethics and disseminationEthics approval is not required as this review does not involve primary data collection. This review will generate level-one evidence regarding the effects of carnosine supplementation on chronic disease risk factors and outcomes and will be disseminated through peer-reviewed publications and at conference meetings to inform future research on the efficacy of carnosine supplementation for the prevention of chronic diseases.Prospero registration numberCRD42017075354.

Project description:It is generally held that the content of several free amino acids and dipeptides is closely related to the energy-supplying metabolism of skeletal muscles. Metabolic characteristics of muscles are involved in the variability of meat quality due to their ability to influence the patterns of energy metabolism not only in living animal but also during postmortem time. Within this context, this study aimed at establishing whether the concentration of histidine dipeptides can affect muscle postmortem metabolism, examining the glycolytic pathway of 3 chicken muscles (pectoralis major, extensor iliotibialis lateralis, and gastrocnemius internus as glycolytic, intermediate, and oxidative-type, respectively) selected based on their histidine dipeptides content and ultimate pH. Thus, a total of 8 carcasses were obtained from the same flock of broiler chickens (Ross 308 strain, females, 49 d of age, 2.8 kg body weight at slaughter) and selected immediately after evisceration from the line of a commercial processing plant. Meat samples of about 1 cm3 were excised from bone-in muscles at 15, 60, 120, and 1,440 min postmortem, instantly frozen in liquid nitrogen and used for the determination of pH, glycolytic metabolites, buffering capacity as well as histidine dipeptides content through 1H-NMR. Overall results suggest that glycolysis in leg muscles ceased already after 2 h postmortem, whereas in breast muscle continued until 24 h, when it exhibited significantly lower pH values (P < 0.05). However, considering its remarkable glycolytic potential, pectoralis major muscle should have exhibited a greater and faster acidification, suggesting that its higher (P < 0.05) histidine dipeptides' content might have prevented a potentially stronger acidification process. Accordingly, breast muscle also showed greater (P < 0.05) buffering ability in the pH range 6.0-7.0. Therefore, anserine and carnosine, being highly positively correlated with muscle's buffering capacity (P < 0.001), might play a role in regulating postmortem pH decline, thus exerting an effect on muscle metabolism during prerigor phase and the quality of the forthcoming meat. Overall results also suggest that total histidine dipeptides content along with muscular ultimate pH represent good indicators for the energy-supplying metabolism of chicken muscles.

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2-Oxo-histidine-containing dipeptides are functional oxidation products.

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2-Oxo-histidine-containing dipeptides are functional oxidation products.

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