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Magnetic Resonance in Medicine Sep 2022To detect carnosine, anserine and homocarnosine in vivo with chemical exchange saturation transfer (CEST) at 17.2 T.
PURPOSE
To detect carnosine, anserine and homocarnosine in vivo with chemical exchange saturation transfer (CEST) at 17.2 T.
METHODS
CEST MR acquisitions were performed using a CEST-linescan sequence developed in-house and optimized for carnosine detection. In vivo CEST data were collected from three different regions of interest (the lower leg muscle, the olfactory bulb and the neocortex) of eight rats.
RESULTS
The CEST effect for carnosine, anserine and homocarnosine was characterized in phantoms, demonstrating the possibility to separate individual contributions by employing high spectral resolution (0.005 ppm) and low CEST saturation power (0.15 T). The CEST signature of these peptides was evidenced, in vivo, in the rat brain and skeletal muscle. The presence of carnosine and anserine in the muscle was corroborated by in vivo localized spectroscopy (MRS). However, the sensitivity of MRS was insufficient for carnosine and homocarnosine detection in the brain. The absolute amounts of carnosine and derivatives in the investigated tissues were determined by liquid chromatography-electrospray ionization-tandem mass spectrometry using isotopic dilution standard methods and were in agreement with the CEST results.
CONCLUSION
The robustness of the CEST-linescan approach and the favorable conditions for CEST at ultra-high magnetic field allowed the in vivo CEST MR detection of carnosine and related peptides. This approach could be useful to investigate noninvasively the (patho)-physiological roles of these molecules.
Topics: Animals; Anserine; Brain; Carnosine; Mass Spectrometry; Muscle, Skeletal; Rats
PubMed: 35526234
DOI: 10.1002/mrm.29282 -
Nutrients Jan 2021The worldwide increase in the number of patients with dementia is becoming a growing problem, while Alzheimer's disease (AD), a primary neurodegenerative disorder,... (Review)
Review
The worldwide increase in the number of patients with dementia is becoming a growing problem, while Alzheimer's disease (AD), a primary neurodegenerative disorder, accounts for more than 70% of all dementia cases. Research on the prevention or reduction of AD occurrence through food ingredients has been widely conducted. In particular, histidine-containing dipeptides, also known as imidazole dipeptides derived from meat, have received much attention. Imidazole dipeptides are abundant in meats such as poultry, fish, and pork. As evidenced by data from recent human intervention trials conducted worldwide, daily supplementation of carnosine and anserine, which are both imidazole dipeptides, can improve memory loss in the elderly and reduce the risk of developing AD. This article also summarizes the latest researches on the biochemical properties of imidazole dipeptides and their effects on animal models associated with age-related cognitive decline. In this review, we focus on the results of human intervention studies using supplements of poultry-derived imidazole dipeptides, including anserine and carnosine, affecting the preservation of cognitive function in the elderly, and discuss how imidazole dipeptides act in the brain to prevent age-related cognitive decline and the onset of dementia.
Topics: Aged; Alzheimer Disease; Animals; Anserine; Brain; Carnosine; Cognition; Cognitive Dysfunction; Dietary Supplements; Dipeptides; Disease Models, Animal; Humans; Imidazoles; Randomized Controlled Trials as Topic
PubMed: 33513893
DOI: 10.3390/nu13020397 -
Journal of Cachexia, Sarcopenia and... Aug 2023Muscle wasting during cancer cachexia is mediated by protein degradation via autophagy and ubiquitin-linked proteolysis. These processes are sensitive to changes in...
BACKGROUND
Muscle wasting during cancer cachexia is mediated by protein degradation via autophagy and ubiquitin-linked proteolysis. These processes are sensitive to changes in intracellular pH ([pH] ) and reactive oxygen species, which in skeletal muscle are partly regulated by histidyl dipeptides, such as carnosine. These dipeptides, synthesized by the enzyme carnosine synthase (CARNS), remove lipid peroxidation-derived aldehydes, and buffer [pH] . Nevertheless, their role in muscle wasting has not been studied.
METHODS
Histidyl dipeptides in the rectus abdominis (RA) muscle and red blood cells (RBCs) of male and female controls (n = 37), weight stable (WS: n = 35), and weight losing (WL; n = 30) upper gastrointestinal cancer (UGIC) patients, were profiled by LC-MS/MS. Expression of enzymes and amino acid transporters, involved in carnosine homeostasis, was measured by Western blotting and RT-PCR. Skeletal muscle myotubes were treated with Lewis lung carcinoma conditioned medium (LLC CM), and β-alanine to study the effects of enhancing carnosine production on muscle wasting.
RESULTS
Carnosine was the predominant dipeptide present in the RA muscle. In controls, carnosine levels were higher in men (7.87 ± 1.98 nmol/mg tissue) compared with women (4.73 ± 1.26 nmol/mg tissue; P = 0.002). In men, carnosine was significantly reduced in both the WS (5.92 ± 2.04 nmol/mg tissue, P = 0.009) and WL (6.15 ± 1.90 nmol/mg tissue; P = 0.030) UGIC patients, compared with controls. In women, carnosine was decreased in the WL UGIC (3.42 ± 1.33 nmol/mg tissue; P = 0.050), compared with WS UGIC patients (4.58 ± 1.57 nmol/mg tissue), and controls (P = 0.025). Carnosine was significantly reduced in the combined WL UGIC patients (5.12 ± 2.15 nmol/mg tissue) compared with controls (6.21 ± 2.24 nmol/mg tissue; P = 0.045). Carnosine was also significantly reduced in the RBCs of WL UGIC patients (0.32 ± 0.24 pmol/mg protein), compared with controls (0.49 ± 0.31 pmol/mg protein, P = 0.037) and WS UGIC patients (0.51 ± 0.40 pmol/mg protein, P = 0.042). Depletion of carnosine diminished the aldehyde-removing ability in the muscle of WL UGIC patients. Carnosine levels were positively associated with decreases in skeletal muscle index in the WL UGIC patients. CARNS expression was decreased in the muscle of WL UGIC patients and myotubes treated with LLC-CM. Treatment with β-alanine, a carnosine precursor, enhanced endogenous carnosine production and decreased ubiquitin-linked protein degradation in LLC-CM treated myotubes.
CONCLUSIONS
Depletion of carnosine could contribute to muscle wasting in cancer patients by lowering the aldehyde quenching abilities. Synthesis of carnosine by CARNS in myotubes is particularly affected by tumour derived factors and could contribute to carnosine depletion in WL UGIC patients. Increasing carnosine in skeletal muscle may be an effective therapeutic intervention to prevent muscle wasting in cancer patients.
Topics: Female; Humans; Male; Aldehydes; beta-Alanine; Carcinoma, Lewis Lung; Carnosine; Chromatography, Liquid; Dipeptides; Muscle, Skeletal; Muscular Atrophy; Tandem Mass Spectrometry; Ubiquitins
PubMed: 37199284
DOI: 10.1002/jcsm.13258 -
American Journal of Physical Medicine &... Jan 2022A 61-yr-old female equestrian presented after 2 wks of left medial thigh pain, which developed suddenly while exiting a car. She denied any history of recent trauma or...
A 61-yr-old female equestrian presented after 2 wks of left medial thigh pain, which developed suddenly while exiting a car. She denied any history of recent trauma or falls. On examination, she was found to have tenderness at the left distal medial thigh with a palpable region of decreased tissue volume at the gracilis myotendinous junction. Point-of-care ultrasound and magnetic resonance imaging confirmed a high-grade partial thickness tear of the left distal gracilis at the myotendinous junction, as well as pes anserine bursal distention. She received physical therapy and underwent a 1-time ultrasound-guided corticosteroid injection to the left pes anserine bursa. At follow-up, her symptoms had significantly improved, and she had returned to horseback riding after 12 wks. Isolated gracilis myotendinous tear is a rare condition, and this is a unique case with an atypical mechanism of injury as gracilis injuries have only been reported during vigorous exercise-related activities rather than transitional movements. This case illustrates the potential increased risk of distal gracilis injury after repetitive corticosteroid injections (genicular nerve blocks and radiofrequency lesioning) in a patient who was also likely predisposed to gracilis microtrauma due to her equestrian activities. Gracilis injury should be considered in the differential diagnosis of distal medial thigh pain, especially in cases with similar interventional and recreational profiles.
Topics: Animals; Athletic Injuries; Diagnosis, Differential; Female; Gracilis Muscle; Horses; Humans; Middle Aged; Musculoskeletal Pain; Tendon Injuries; Thigh
PubMed: 34320562
DOI: 10.1097/PHM.0000000000001854 -
Biochemical and Biophysical Research... Jul 2022Carnosine and anserine are abundant peptides found in the skeletal muscle and nervous system in many vertebrates. Several in vitro and in vivo studies have demonstrate...
Carnosine and anserine are abundant peptides found in the skeletal muscle and nervous system in many vertebrates. Several in vitro and in vivo studies have demonstrate that exogenously administered carnosine improves exercise performance. Furthermore, carnosine is an antioxidant and antifatigue supplement. However, the physiological functions of endogenous carnosine and its related histidine-containing dipeptides in a living organism remain unclear. We aimed to clarify the physiological roles of endogenous carnosine by investigating the characteristics of carnosine synthase gene-deficient mice and the effects of carnosine on skeletal muscle protein metabolism. We discovered that carnosine and anserine were undetectable in the skeletal muscle of carnosine synthase knockout mice. We also quantified protein gene expression and enzyme levels in muscle protein metabolism. Gene and protein levels of the muscle protein synthesizer insulin-like growth factor-1 (IGF-1) and the degrading enzyme cathepsin B were markedly lower in carnosine synthase gene-deficient mice than those in wild-type mice. The amount of 3-methylhistidine (a marker for muscle proteolysis) in forced exercise and the weight of the gastrocnemius muscle were considerably lower in carnosine synthase gene-deficient mice than in wild-type mice. Consequently, we showed that carnosine deficiency affects weight maintenance and protein metabolism in skeletal muscle, suggesting that carnosine regulates skeletal muscle protein metabolism.
Topics: Animals; Anserine; Carnosine; Dipeptides; Mice; Muscle Proteins; Muscle, Skeletal; Peptide Synthases
PubMed: 35500438
DOI: 10.1016/j.bbrc.2022.04.075 -
Scientific Reports Apr 2023Balenine possesses some of carnosine's and anserine's functions, yet it appears more resistant to the hydrolysing CN1 enzyme. The aim of this study was to elucidate the...
Balenine possesses some of carnosine's and anserine's functions, yet it appears more resistant to the hydrolysing CN1 enzyme. The aim of this study was to elucidate the stability of balenine in the systemic circulation and its bioavailability in humans following acute supplementation. Two experiments were conducted in which (in vitro) carnosine, anserine and balenine were added to plasma to compare degradation profiles and (in vivo) three increasing doses (1-4-10 mg/kg) of balenine were acutely administered to 6 human volunteers. Half-life of balenine (34.9 ± 14.6 min) was respectively 29.1 and 16.3 times longer than that of carnosine (1.20 ± 0.36 min, p = 0.0044) and anserine (2.14 ± 0.58 min, p = 0.0044). In vivo, 10 mg/kg of balenine elicited a peak plasma concentration (Cmax) of 28 µM, which was 4 and 18 times higher than with 4 (p = 0.0034) and 1 mg/kg (p = 0.0017), respectively. CN1 activity showed strong negative correlations with half-life (ρ = - 0.829; p = 0.0583), Cmax (r = - 0.938; p = 0.0372) and incremental area under the curve (r = - 0.825; p = 0.0433). Overall, balenine seems more resistant to CN1 hydrolysis resulting in better in vivo bioavailability, yet its degradation remains dependent on enzyme activity. Although a similar functionality as carnosine and anserine remains to be demonstrated, opportunities arise for balenine as nutraceutical or ergogenic aid.
Topics: Humans; Carnosine; Anserine; Dietary Supplements
PubMed: 37081019
DOI: 10.1038/s41598-023-33300-1 -
Amino Acids Dec 2015Histidine-containing dipeptides like carnosine and anserine have protective functions in both health and disease. Animal studies suggest that carnosine can be...
Histidine-containing dipeptides like carnosine and anserine have protective functions in both health and disease. Animal studies suggest that carnosine can be metabolized within the kidney. The goal of this study was to obtain evidence of carnosine metabolism in the human kidney and to provide insight with regards to diabetic nephropathy. Expression, distribution, and localization of carnosinase-1 (CNDP1), carnosine synthase (CARNS), and taurine transporters (TauT) were measured in human kidneys. CNDP1 and CARNS activities were measured in vitro. CNDP1 and CARNS were located primarily in distal and proximal tubules, respectively. Specifically, CNDP1 levels were high in tubular cells and podocytes (20.3 ± 3.4 and 15 ± 3.2 ng/mg, respectively) and considerably lower in endothelial cells (0.5 ± 0.1 ng/mg). CNDP1 expression was correlated with the degradation of carnosine and anserine (r = 0.88 and 0.81, respectively). Anserine and carnosine were also detectable by HPLC in the renal cortex. Finally, TauT mRNA and protein were found in all renal epithelial cells. In diabetic patients, CNDP1 seemed to be reallocated to proximal tubules. We report compelling evidence that the kidney has an intrinsic capacity to metabolize carnosine. Both CNDP1 and CARNS are expressed in glomeruli and tubular cells. Carnosine-synthesizing and carnosine-hydrolyzing enzymes are localized in distinct compartments in the nephron and increased CNDP1 levels suggest a higher CNDP1 activity in diabetic kidneys.
Topics: Anserine; Carnosine; Chromatography, High Pressure Liquid; Diabetic Neuropathies; Dipeptidases; Endothelial Cells; Epithelial Cells; Gene Expression Profiling; Gene Expression Regulation; Humans; Hydrolysis; Immunohistochemistry; Kidney; Kidney Tubules; Membrane Glycoproteins; Membrane Transport Proteins; Nephrons; Peptide Synthases; Podocytes; RNA, Messenger
PubMed: 26206726
DOI: 10.1007/s00726-015-2045-7 -
Animal Science Journal = Nihon Chikusan... 2023Functional dipeptides carnosine and anserine are abundant in muscle. We determined the effect of short-term dietary histidine (His) content on muscle carnosine and...
Functional dipeptides carnosine and anserine are abundant in muscle. We determined the effect of short-term dietary histidine (His) content on muscle carnosine and anserine contents and meat quality of broilers. Three groups of 28-day-old female broilers were fed diets with His contents of 67%, 100%, or 150% of requirement for 10 days before market (His contents 0.21%, 0.32%, and 0.48%, respectively). The carnosine and anserine contents of 0-h aged muscle significantly increased with dietary His content; in particular, the carnosine content was 162% higher in the His 0.48% group than in the His 0.32% group. The contents of both peptides also increased with dietary His content in 48-h aged muscle, but carnosine was not detected in 0- and 48-h aged muscle of the His 0.21% group. The drip loss, cooking loss, shear force, and pH of meat were not affected by the dietary His content. The 2-thiobarbituric acid-reactive substances contents of 24- and 48-h aged muscles were lower in the His 0.48% group than in the other groups, and the a* and b* values were lower in the His 0.21% group. These results suggest that short-term dietary His content affects imidazole dipeptide contents, antioxidative capacity, and color of broiler meat.
Topics: Animals; Female; Carnosine; Anserine; Histidine; Chickens; Muscles; Dipeptides; Diet; Meat
PubMed: 37528620
DOI: 10.1111/asj.13856 -
Free Radical Research Jun 2021Imidazole-containing dipeptides (IDPs), such as carnosine and anserine, are endogenously produced and have been shown to function as antioxidants. Recently, we have...
Imidazole-containing dipeptides (IDPs), such as carnosine and anserine, are endogenously produced and have been shown to function as antioxidants. Recently, we have characterized the endogenous production of 2-oxo-imidazole-containing dipeptides (2-oxo-IDPs), such as 2-oxo-carnosine, 2-oxo-anserine, and 2-oxo-homocarnosine in mouse tissues, including brain, and demonstrated that 2-oxo-IDPs exhibit higher antioxidant activities than the corresponding IDPs. In this study, we established a highly sensitive, specific, and quantitative method for the detection of the IDP homoanserine and its oxidized derivative 2-oxo-homoanserine high-performance liquid chromatography tandem mass spectrometry coupled with a stable-isotope dilution method, and quantitatively analyzed its tissue distribution and age-related intra-brain distribution in C57BL/6J mice. The quantitative analysis revealed that homoanserine exists abundantly not only in the mouse brain but also in other tissues, such as the muscle and lungs. Further, we successfully detected the endogenous production of 2-oxo-homoanserine in the mouse brain. The mass spectrometric analysis revealed that homoanserine predominantly exists in the cerebrum and cerebellum and the concentrations in 10-week-old mice were approximately 50-fold higher than those in 1-week-old mice. Accordingly, this is the first study that reports the spatial and temporal expression patterns of homoanserine and its 2-oxo derivative in C57BL/6J mice.
Topics: Animals; Chromatography, High Pressure Liquid; Imidazoles; Mass Spectrometry; Mice; Serine; Tissue Distribution
PubMed: 34160331
DOI: 10.1080/10715762.2021.1888945 -
Nutrients Apr 2020The study tested whether anserine (beta-alanyl-3-methyl-l-histidine), the active ingredient of chicken essence affects exercise-induced oxidative stress, cell integrity,... (Randomized Controlled Trial)
Randomized Controlled Trial
The study tested whether anserine (beta-alanyl-3-methyl-l-histidine), the active ingredient of chicken essence affects exercise-induced oxidative stress, cell integrity, and haematology biomarkers. In a randomized placebo-controlled repeated-measures design, ten healthy men ingested anserine in either a low dose (ANS-LD) 15 mg.kg.bw, high dose (ANS-HD) 30 mg.kg.bw, or placebo (PLA), following an exercise challenge (time to exhaustion), on three separate occasions. Anserine supplementation increased superoxide dismutase (SOD) by 50% ( < 0.001, effect size d = 0.8 for both ANS-LD and ANS-HD), and preserved catalase (CAT) activity suggesting an improved antioxidant activity. However, both ANS-LD and ANS-HD elevated glutathione disulfide (GSSG), (both < 0.001, main treatment effect), and consequently lowered the glutathione to glutathione disulfide (GSH/GSSG) ratio compared with PLA ( < 0.01, main treatment effect), without significant effects on thiobarbituric acid active reactive substances (TBARS). Exercise-induced cell damage biomarkers of glutamic-oxaloacetic transaminase (GOT) and myoglobin were unaffected by anserine. There were slight but significant elevations in glutamate pyruvate transaminase (GPT) and creatine kinase isoenzyme (CKMB), especially in ANS-HD ( < 0.05) compared with ANS-LD or PLA. Haematological biomarkers were largely unaffected by anserine, its dose, and without interaction with post exercise time-course. However, compared with ANS-LD and PLA, ANS-HD increased the mean cell volume (MCV), and decreased the mean corpuscular haemoglobin concentration (MCHC) ( < 0.001). Anserine preserves cellular homoeostasis through enhanced antioxidant activity and protects cell integrity in healthy men, which is important for chronic disease prevention. However, anserine temporal elevated exercise-induced cell-damage, together with enhanced antioxidant activity and haematological responses suggest an augmented exercise-induced adaptative response and recovery.
Topics: Adult; Anserine; Antioxidants; Catalase; Cell Size; Cross-Over Studies; Dietary Supplements; Exercise; Glutathione; Glutathione Disulfide; Healthy Volunteers; Hemoglobins; Homeostasis; Humans; Male; Oxidative Stress; Superoxide Dismutase; Young Adult
PubMed: 32325914
DOI: 10.3390/nu12041146