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Reduced muscle carnosine content in type 2, but not in type 1 diabetic patients

Gualano, Bruno; Everaert, Inge; Stegen, Sanne; Artioli, Guilherme Giannini; Taes, Youri; Roschel, Hamilton; Achten, Eric; Otaduy, Maria Concepcion; Lancha Junior, Antonio Herbert; Harris, Roger; Derave, Wim
Fonte: SPRINGER; NEW YORK Publicador: SPRINGER; NEW YORK
Tipo: Artigo de Revista Científica
ENG
Relevância na Pesquisa
37.99691%
Carnosine is present in high concentrations in skeletal muscle where it contributes to acid buffering and functions also as a natural protector against oxidative and carbonyl stress. Animal studies have shown an anti-diabetic effect of carnosine supplementation. High carnosinase activity, the carnosine degrading enzyme in serum, is a risk factor for diabetic complications in humans. The aim of the present study was to compare the muscle carnosine concentration in diabetic subjects to the level in non-diabetics. Type 1 and 2 diabetic patients and matched healthy controls (total n = 58) were included in the study. Muscle carnosine content was evaluated by proton magnetic resonance spectroscopy (3 Tesla) in soleus and gastrocnemius. Significantly lower carnosine content (-45%) in gastrocnemius muscle, but not in soleus, was shown in type 2 diabetic patients compared with controls. No differences were observed in type 1 diabetic patients. Type II diabetic patients display a reduced muscular carnosine content. A reduction in muscle carnosine concentration may be partially associated with defective mechanisms against oxidative, glycative and carbonyl stress in muscle.; Research Foundation-Flanders (FWO) [1.5.149.08, G.0046.09]; ResearchFoundation Flanders (FWO); Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2005/56464-9...

Evaluation of radioprotective effect of carnosine (beta- alanyl-1- histidine) on the wound healing in rats

Tanaka,Rosana Aramaki; Ramos,Flávia Maria de Moraes; Almeida,Solange Maria de; Vizioli,Mário Roberto; Bóscolo,Frab Norberto
Fonte: Faculdade De Odontologia De Bauru - USP Publicador: Faculdade De Odontologia De Bauru - USP
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/09/2005 EN
Relevância na Pesquisa
38.026387%
The purpose of this study was to evaluate the radioprotective effect of carnosine (beta- alanyl-1-histidine) on the wound healing in rats. Therefore, 48 male rats were submitted to a surgical procedure to perform a rectangular wound in the anterior-dorsal region. The animals were divided into 4 experimental groups randomly chosen: control; irradiated; carnosine irradiated and carnosine group. The irradiated and carnosine irradiated group were exposed to a dose (6Gy) of gamma irradiation, in the whole body, 72 hours after surgery. The carnosine and carnosine irradiated groups, in addition to the surgical procedure and the irradiation, received two doses of carnosine aqueous solution, the first one being injected 48 hours after surgery, and the second one 1 hour and 30 minutes before irradiation. The tissue repair of the 4 groups was evaluated at 4, 7, 14, and 21 days after inflicting the wound, by morphological, histochemical and histophysical methods. At all examined periods, it could be observed that the animals from the carnosine irradiated group presented a better developed granulation tissue than the irradiated group and closely similar to that of the control group. Thus, under the experimental conditions used, it was possible to conclude that carnosine is an effective radioprotective substance.

Promotion of Crown-Gall Tumor Growth by Lysopine, Octopine, Nopaline, and Carnosine 1

Lippincott, James A.; Lippincott, Barbara B.; Chang, Chi-Cheng
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1972 EN
Relevância na Pesquisa
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The growth of crown-gall tumors on primary bean leaves (Phaseolus vulgaris L. cv. “Pinto”) was promoted by the addition of d-lysopine, d-octopine, l-carnosine, or nopaline. Assayed on tumors induced by Agrobacterium tumefaciens strain B6, the relative activity was octopine = carnosine > lysopine ≫ nopaline; assayed on tumors induced by A. tumefaciens strain T-37, which induces tumors which form nopaline, the relative activity was nopaline = octopine = carnosine > lysopine. From one to three applications of carnosine or octopine gave equal additive increments in tumor growth, showing that a continual supply of these substances is required to maintain an increased rate of growth. At concentrations above 0.1 mm, pairs of these growth-promoting substances were less active than when applied singly. Inhibition of octopine-induced growth was obtained by applying 0.01 mm carnosine with 1 mm octopine and partial inhibition was obtained when carnosine was added 10 hr after octopine. Equimolar mixtures of lysopine, octopine, and carnosine, however, were at least as active in promoting tumor growth as any of the compounds added singly at equivalent concentrations. The activity of 0.1 to 0.5 mm lysopine, octopine, and carnosine was inhibited...

Estimation of the carnosine content of different fibre types in the middle gluteal muscle of the thoroughbred horse.

Sewell, D A; Harris, R C; Marlin, D J; Dunnett, M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/1992 EN
Relevância na Pesquisa
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1. Skeletal muscle samples were obtained by needle biopsy from one of two depths of the m. gluteus medius in a group of twenty race-trained thoroughbred horses. 2. The content of carnosine was determined in each muscle sample, part of which was used for histochemical analysis. Fibres were classified as type I, type IIA or type IIB on the basis of the pH dependent lability of the myosin ATPase reaction. 3. Muscle samples with a higher type II fibre section area (FSA) have a higher carnosine content than those with a higher type I FSA. 4. Multiple linear regression analysis was used to estimate the mean carnosine content of individual fibre types. The results estimated a mean carnosine content in type I fibres of 54 mmol (kg dry muscle (DM))-1, in type IIA fibres 85 mmol (kg DM)-1 and in type IIB fibres 180 mmol (kg DM)-1. 5. Based on the estimated values of single fibre carnosine content, there was close concordance between the estimated and the measured carnosine content of mixed fibre samples. 6. It would appear from this and other studies that carnosine has an important role as a physico-chemical buffer in equine middle gluteal muscle and that this is greatest in type IIB fibres, where it may account for up to 50% of physico-chemical buffering of H+ produced by muscle in the pH range 7.1-6.5.

Intestinal absorption of the intact peptide carnosine in man, and comparison with intestinal permeability to lactulose.

Gardner, M L; Illingworth, K M; Kelleher, J; Wood, D
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1991 EN
Relevância na Pesquisa
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1. Healthy humans ingested the dipeptide carnosine (L-beta-alanyl-L-histidine). Their plasma levels and urinary outputs of carnosine and beta-alanine were monitored over the following 5 h. 2. Large amounts of intact carnosine (up to 14% of the ingested dose) were recovered in the urine over the 5 h after ingestion. However, carnosine was undetectable in the plasma unless precautions were taken to inhibit blood carnosinase activity ex vivo during and after blood collection. 3. The amount of carnosine recovered in urine varied substantially between subjects. It correlated negatively with carnosinase enzymic activity in the plasma. Highest carnosinase activities were observed in those subjects who regularly underwent physical training. 4. Urinary recovery of the disaccharide lactulose also varied considerably between subjects, but was substantially lower than that of carnosine. There was no significant correlation between the recoveries of carnosine and lactulose. 5. When lactulose was ingested with a hypertonic solution, the urinary recovery of lactulose was generally increased. When carnosine was ingested with a hypertonic solution, the urinary recovery of carnosine was reduced: hence the paracellular route probably is not dominant for absorption of intact carnosine. 6. Intact carnosine must have crossed the intestine to an extent much greater than hitherto recognized. Rapid post-absorptive hydrolysis is a severe obstacle to quantification of intact peptide absorption.

Impairment of jejunal absorption rate of carnosine by glycylglycine in man in vivo.

Cook, G C
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1976 EN
Relevância na Pesquisa
28.026387%
Using a double-lumen tube jejunal perfusion system in vivo, the mutual effects of carnosine (beta-alanyl-L-histidine) and glycylglycine on their respective absorption rates have been studied in six Zambian African adults. Data on the effect of the constituent amino-acids of carnosine on glycylglycine absorption rate have similarly been obtained. The solutions infused in each subject contained (A) carnosine (50 mmol l.-1), (B) carnosine (50 mmol l.-1) and glycylglycine (50 mmol l.-1), (C) glycylglycine (50 mmol l.-1), and (D) glycylglycine (50 mmol l.-1), L-histidine (50 mmol l.-1) and beta-alanine (50 mmol l.-1). Glycylglycine produced a significant impairment in the mean rate of histidine absorption from carnosine (P less than 0-01). However, carnosine did not have a significant effect on the mean rate of glycine absorption from glycylglycine. Mean rate of histidine absorption from solution D was significantly higher than that from solution A (P less than 0-01). Mean rate of glycine absorption from glycylglycine was not significantly different during infusion of solutions B, C, and D. The results are consistent with the concept that carnosine on glycylglycine is probably because the affinity of mechanism; the lack of influence of carnosine on glycylglycine is probably because the affinity of carnosine for the dipeptide uptake mechanism is relatively low. A gross difference has been shown between mean absorption rate of histidine from free L-histidine (solution D) (25-8 mmol h-1) and when it is given in the form of carnosine in the presence of another dipeptide (solution B) (8-7 mmol h-1); that emphasizes the complexity of amino acid and peptide interaction during absorption...

Influence of genetic knockout of Pept2 on the in vivo disposition of endogenous and exogenous carnosine in wild-type and Pept2 null mice

Kamal, Mohamed A.; Jiang, Huidi; Hu, Yongjun; Keep, Richard. F.; Smith, David E.
Fonte: American Physiological Society Publicador: American Physiological Society
Tipo: Artigo de Revista Científica
EN
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Carnosine (β-alanyl-l-histidine), an endogenous dipeptide substrate of the proton-coupled oligopeptide transporter PEPT2, plays an important role in many physiological processes. This study examined the effect of PEPT2 on the disposition of endogenous and exogenous carnosine in wild-type and Pept2 null mice. After exogenous dosing of [3H]carnosine (1 nmol/g iv bolus), a marked increase was observed in its systemic clearance in Pept2 null mice (0.50 vs. 0.29 ml/min), resulting in a decreased systemic exposure of dipeptide (area under the curve = 43.7 vs. 73.0 min×μM). Carnosine uptake was substantially reduced in the kidney of Pept2 null mice, and renal clearance increased 18-fold in this genotype (206 vs. 11.5 μl/min). Fractional reabsorption of carnosine in Pept2 null mice was only one-fifth that in wild-type animals (0.20 vs. 0.94). PEPT2 also had a substantial impact in brain where the cerebrospinal fluid (CSF)-to-plasma concentration ratio of carnosine was eightfold greater in Pept2 null mice (0.70 vs. 0.08). With respect to endogenous carnosine levels, significant reductions were observed in Pept2 null compared with wild-type mice for choroid plexus (0.026 vs. 0.20 mmol/kg), olfactory bulb (1.12 vs. 1.79 mmol/kg), and spleen (0.019 vs. 0.029 mmol/kg). In contrast...

Effects of carnosine on the evoked potentials in hippocampal CA1 region*

Feng, Zhou-yan; Zheng, Xiao-jing; Wang, Jing
Fonte: Zhejiang University Press Publicador: Zhejiang University Press
Tipo: Artigo de Revista Científica
Publicado em /07/2009 EN
Relevância na Pesquisa
27.918728%
Objective: To directly examine the effects of carnosine on neuronal excitation and inhibition in rat hippocampus in vivo. Methods: Artificial cerebrospinal fluid with carnosine was directly administrated over the exposed rat hippocampus. The changes of neuron activity in the CA1 region of hippocampus were evaluated by orthodromically- and antidromically-evoked potentials, as well as paired-pulse stimulation paradigm. Results: In both orthodromic and antidromic response potentials, carnosine transformed population spikes (PSs) with single spike into epileptiform multiple spikes. In addition, similar to the effect of γ-aminobutyric acidA (GABAA) antagonist picrotoxin, carnosine decreased paired-pulse stimulating depression significantly. However, no significant change was observed in the spontaneous field potentials during the application of carnosine. Conclusion: The results indicate a disinhibition-induced excitation effect of carnosine on the CA1 pyramidal neurons. It provides important information against the application of carnosine as a potential anticonvulsant in clinical treatment.

Differential Neuroprotective Effects of Carnosine, Anserine, and N-Acetyl Carnosine against Permanent Focal Ischemia

Min, Jiangyong; Senut, Marie-Claude; Rajanikant, Krishnamurthy; Greenberg, Eric; Bandagi, Ram; Zemke, Daniel; Mousa, Ahmad; Kassab, Mounzer; Farooq, Muhammad U.; Gupta, Rishi; Majid, Arshad
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/2008 EN
Relevância na Pesquisa
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Carnosine (β-alanyl-L-histidine) has been shown to exhibit neuroprotection in rodent models of cerebral ischemia. In the present study, we further characterized the effects of carnosine treatment in a mouse model of permanent focal cerebral ischemia and compared them with its related peptides anserine and N-acetylated carnosine. We also evaluated the efficacy of bestatin, a carnosinase inhibitor, in ameliorating ischemic brain damage. Permanent focal cerebral ischemia was induced by occlusion of the middle cerebral artery (pMCAO). Mice were subsequently randomly assigned to receive an intraperitoneal injection of vehicle (0.9% saline), carnosine, N-acetyl carnosine, anserine, bestatin alone, or bestatin with carnosine. Infarct size was examined using 2,3,5-triphenyltetrazolium chloride staining 1, 3, and 7 days following pMCAO, and neurological function was evaluated using an 18-point-based scale. Brain levels of carnosine were measured in treated mice using high-performance liquid chromatography 1 day following pMCAO. We demonstrated that treatment with carnosine, but not its analogues, was able to significantly reduce infarct volume and improve neurological function compared with those in vehicle-treated mice. These beneficial effects were maintained for 7 days post-pMCAO. In contrast...

Molecular Identification of Carnosine Synthase as ATP-grasp Domain-containing Protein 1 (ATPGD1)*

Drozak, Jakub; Veiga-da-Cunha, Maria; Vertommen, Didier; Stroobant, Vincent; Van Schaftingen, Emile
Fonte: American Society for Biochemistry and Molecular Biology Publicador: American Society for Biochemistry and Molecular Biology
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
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Carnosine (β-alanyl-l-histidine) and homocarnosine (γ-aminobutyryl-l-histidine) are abundant dipeptides in skeletal muscle and brain of most vertebrates and some invertebrates. The formation of both compounds is catalyzed by carnosine synthase, which is thought to convert ATP to AMP and inorganic pyrophosphate, and whose molecular identity is unknown. In the present work, we have purified carnosine synthase from chicken pectoral muscle about 1500-fold until only two major polypeptides of 100 and 90 kDa were present in the preparation. Mass spectrometry analysis of these polypeptides did not yield any meaningful candidate. Carnosine formation catalyzed by the purified enzyme was accompanied by a stoichiometric formation, not of AMP, but of ADP, suggesting that carnosine synthase belongs to the “ATP-grasp family” of ligases. A data base mining approach identified ATPGD1 as a likely candidate. As this protein was absent from chicken protein data bases, we reconstituted its sequence from a PCR-amplified cDNA and found it to fit with the 100-kDa polypeptide of the chicken carnosine synthase preparation. Mouse and human ATPGD1 were expressed in HEK293T cells, purified to homogeneity, and shown to catalyze the formation of carnosine...

Anti-Stress Effects of Carnosine on Restraint-Evoked Immunocompromise in Mice through Spleen Lymphocyte Number Maintenance

Li, Yi-Fang; He, Rong-Rong; Tsoi, Bun; Li, Xiao-Di; Li, Wei-Xi; Abe, Keiichi; Kurihara, Hiroshi
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 12/04/2012 EN
Relevância na Pesquisa
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Carnosine (β-alanyl-L-histidine), a naturally occurring dipeptide, has been characterized as a putative neurotransmitter and serves as a reservoir for brain histamine, which could act on histaminergic neurons system to relieve stress-induced damages. However, understanding of the role of carnosine in stress-evoked immunocompromise is limited. In this study, results showed that when mice were subjected to restraint stress, spleen index and the number of spleen lymphocytes including Natural Killer (NK) cells were obviously decreased. Results also demonstrated that restraint stress decreased the cytotoxic activity of NK cells per spleen (LU10/spleen) while the activity of a single NK cell (LU10/106 cells) was not changed. However, oral administration of carnosine (150 and 300 mg/kg) increased spleen index and number of spleen lymphocytes (including NK cells), and elevated the cytotoxic activity of NK cells per spleen in restraint-stressed mice. These results indicated that carnosine ameliorated stress-evoked immunocompromise through spleen lymphocyte number maintenance. Carnosine was further found to reduce stress-induced elevation of plasma corticosterone level. On the other hand, results showed that carnosine and RU486 (a glucocorticoids receptor antagonist) treatment prevented the reduction in mitochondrion membrane potential and the release of mitochondrial cytochrome c into cytoplasm...

L-Carnosine Affects the Growth of Saccharomyces cerevisiae in a Metabolism-Dependent Manner

Cartwright, Stephanie P.; Bill, Roslyn M.; Hipkiss, Alan R.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 12/09/2012 EN
Relevância na Pesquisa
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The dipeptide L-carnosine (β-alanyl-L-histidine) has been described as enigmatic: it inhibits growth of cancer cells but delays senescence in cultured human fibroblasts and extends the lifespan of male fruit flies. In an attempt to understand these observations, the effects of L-carnosine on the model eukaryote, Saccharomyces cerevisiae, were examined on account of its unique metabolic properties; S. cerevisiae can respire aerobically, but like some tumor cells, it can also exhibit a metabolism in which aerobic respiration is down regulated. L-Carnosine exhibited both inhibitory and stimulatory effects on yeast cells, dependent upon the carbon source in the growth medium. When yeast cells were not reliant on oxidative phosphorylation for energy generation (e.g. when grown on a fermentable carbon source such as 2% glucose), 10–30 mM L-carnosine slowed growth rates in a dose-dependent manner and increased cell death by up to 17%. In contrast, in media containing a non-fermentable carbon source in which yeast are dependent on aerobic respiration (e.g. 2% glycerol), L-carnosine did not provoke cell death. This latter observation was confirmed in the respiratory yeast, Pichia pastoris. Moreover, when deletion strains in the yeast nutrient-sensing pathway were treated with L-carnosine...

Antioxidant effect of carnosine pretreatment on cisplatin-induced renal oxidative stress in rats

Noori, S.; Mahboob, Tabassum
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
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Cisplatin mediated nephrotoxicity is remarkably documented by reactive oxygen species. Carnosine is a naturally occurring dipeptide and has a scavenging property. The aim of present study was to assess the lipid peroxidation and antioxidant enzymes in association with oxidative stress in cisplatin -treated and 10 subsequent doses of carnosine-pretreated rats. 24 male Albino Wistar rats, were randomly divided into four groups (n=6). Group I remains untreated; Group II received Cisplatin (3 mg / kg) for 5 alternate days; Group III received Carnosine (10 mg / kg) for consecutive 10 days; Group IV received Carnosine (10 mg / kg) before administration of Cisplatin (3 mg / kg). The effects of carnosine on cisplatin-induced nephrotoxicity were evaluated by plasma creatinine, urea, malondialdehyde, nitrate; kidney tissue malondialdehyde, 4-HNE, superoxide dismutase and catalase activities. Cisplatin-induced oxidative stress was indicated by increased level of tissue MDA, 4-HNE and decreased level of tissue GSH, SOD and Catalase. Marked elevation of kidney weight and reduced body weight and pathological changes in kidney tissues were also observed in Cisplatin-treated rats. Carnosine reduced these pathological changes and counteracted the deleterious effects of cisplatin. The results divulge the beneficial effect of Carnosine pretreatment with cisplatin in experimental rat model.

Distribution of carnosine-like peptides in the nervous system of developing and adult zebrafish (Danio rerio) and embryonic effects of chronic carnosine exposure

Senut, Marie-Claude; Azher, Seema; Margolis, Frank L.; Patel, Kamakshi; Mousa, Ahmad; Majid, Arshad
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
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Carnosine-like peptides (carnosine-LP) are a family of histidine derivatives that are present in the nervous system of various species and that exhibit antioxidant, anti-matrix-metalloproteinase, anti-excitotoxic, and free-radical scavenging properties. They are also neuroprotective in animal models of cerebral ischemia. Although the function of carnosine-LP is largely unknown, the hypothesis has been advanced that they play a role in the developing nervous system. Since the zebrafish is an excellent vertebrate model for studying development and disease, we have examined the distribution pattern of carnosine-LP in the adult and developing zebrafish. In the adult, immunoreactivity for carnosine-LP is specifically concentrated in sensory neurons and non-sensory cells of the olfactory epithelium, the olfactory nerve, and the olfactory bulb. Robust staining has also been observed in the retinal outer nuclear layer and the corneal epithelium. Developmental studies have revealed immunostaining for carnosine-LP as early as 18 h, 24 h, and 7 days post-fertilization in, respectively, the olfactory, corneal, and retinal primordia. These data suggest that carnosine-LP are involved in olfactory and visual function. We have also investigated the effects of chronic (7 days) exposure to carnosine on embryonic development and show that 0.01 μM to 10 mM concentrations of carnosine do not elicit significant deleterious effects. Conversely...

The Anti-Proliferative Effect of L-Carnosine Correlates with a Decreased Expression of Hypoxia Inducible Factor 1 alpha in Human Colon Cancer Cells

Iovine, Barbara; Oliviero, Giorgia; Garofalo, Mariangela; Orefice, Maria; Nocella, Francesca; Borbone, Nicola; Piccialli, Vincenzo; Centore, Roberto; Mazzone, Massimiliano; Piccialli, Gennaro; Bevilacqua, Maria Assunta
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 07/05/2014 EN
Relevância na Pesquisa
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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...

Inhibition of the growth of transformed and neoplastic cells by the dipeptide carnosine.

Holliday, R.; McFarland, G. A.
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em /04/1996 EN
Relevância na Pesquisa
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Human diploid fibroblasts growth normally in medium containing physiological concentrations of the naturally occurring dipeptide carnosine (beta-alanyl-L-histidine). These concentrations are cytotoxic to transformed and neoplastic cells lines in modified Eagle medium (MEM), whereas these cells grow vigorously in Dulbecco's modified Eagle medium (DMEM) containing carnosine. This difference is due to the presence of 1 mM sodium pyruvate in DMEM. Seven human cell lines and two rodent cell lines were tested and all are strongly inhibited by carnosine in the absence of pyruvate. Experiments with HeLa cells show that anserine is similar to carnosine, but D-carnosine and homocarnosine are without effect. Also, the non-essential amino acids alanine and glutamic acid contribute to the effect of pyruvate in preventing carnosine toxicity, and oxaloacetate and alpha-ketoglutarate can substitute for pyruvate. We have used mixtures of normal MRC-5 fibroblasts and HeLa cells to demonstrate that 20 mM carnosine can selectively eliminate the tumour cells. This has obvious implications which might be exploited in in vivo and in vitro studies. Carnosine is known to react strongly with aldehyde and keto groups of sugars by Amadori reaction, and we propose that it depletes certain glycolysis intermediates. It is well known that tumour cells are more dependent on glycolysis than normal cells. A reduction of glycolysis intermediates by carnosine may deplete their energy supply...

Intrinsic carnosine metabolism in the human kidney

Peters, Verena; Klessens, Celine Q. F.; Baelde, Hans J.; Singler, Benjamin; Veraar, Kimberley A. M.; Zutinic, Ana; Drozak, Jakub; Zschocke, Johannes; Schmitt, Claus P.; de Heer, Emile
Fonte: Springer Vienna Publicador: Springer Vienna
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
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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.

Analysis of an H1 receptor-mediated, zinc-potentiated vasoconstrictor action of the histidyl dipeptide carnosine in rabbit saphenous vein

O'Dowd, Anne; Miller, David J
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1998 EN
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The contractile action of the dipeptide carnosine (β-alanyl-L-histidine), active as a Zn·carnosine complex (Zn·Carn), was investigated in isolated rings of rabbit saphenous vein (RSV) and was found to be antagonized by the H1 antagonist mepyramine.Mepyramine-sensitive, histamine-induced contractures in RSV, were smaller (73±0.1%) and less well sustained than carnosine-induced contractures.Schild plot values for mepyramine antagonism were, for carnosine-induced contractures; pA2=7.97±0.12, slope=1.33±0.06 (r=0.793) and for histamine-induced contractures; pA2=8.48±0.07, slope=0.63±0.05, r=0.957).Serotonergic antagonists methiothepin and ketanserin, antagonize both carnosine- and histamine-induced contractures in RSV, probably reflecting coincidental inhibition at the H1-receptor.Carnosine, with Zn present, can inhibit the H1-specific binding of [3H]-mepyramine to isolated guinea-pig cerebellar membranes (log IC50s−2.78±0.02, −3.93±0.03 and −4.64±0.03 at 10, 30 and 80 μM Zn respectively; values corrected for the Zn-specific inhibition which has a logIC50 of −4.20).In the radioligand binding assay, the effect of carnosine can be described as a function of Zn·Carn concentration with an apparent logIC50 of −5.61. This value is consistent with that obtained from the functional studies on RSV.Histamine-induced contractures have an indomethacine-sensitive component (27.2±8.3% of control response)...

The dipeptide carnosine constricts rabbit saphenous vein as a zinc complex apparently via a serotonergic receptor.

O'Dowd, A; O'Dowd, J J; Miller, D J
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/09/1996 EN
Relevância na Pesquisa
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1. The endogenous dipeptide carnosine (beta-alanyl-L-histidine), at 0.1-10 mM, provokes sustained contractures in rabbit saphenous vein rings with greater efficacy than noradrenaline (NA). 2. The effects of carnosine are specific; anserine and homocarnosine are ineffective, as are carnosine's constituent amino acids histidine and beta-alanine. 3. Maximum carnosine-induced tension is enhanced by Zn ions (e.g. to 127.5 +/- 13.1% of control at 10 microM total Zn concentration, Zntot) and the sensitivity to carnosine potentiated (mean [carnosine] required for half-maximal tension, K1/2, reduced from 1.23 mM to 17.0 microM carnosine with 15 microM Zntot). 4. The dipeptide apparently acts as a zinc-carnosine complex. The effects of carnosine at concentrations of 1 microM to 10 mM in the presence of 1-100 microM Zntot, can be described as a unique function of the concentration of Zn-carnosine, with an apparent K1/2 for the complex of 7.4 x 10(-8) M. 5. Contractures are reduced at low [Ca2+], unaffected by adrenoceptor antagonists, but can be blocked by serotonergic receptor antagonists including ketanserin and methiothepin. 6. Competition between albumin and carnosine for Zn ions, as might occur in plasma, can be demonstrated experimentally. 7. The mode of action of carnosine is virtually unique: a vascular muscle receptor apparently transduces the action of a dipeptide in the form of a metal chelate.

Evaluation of radioprotective effect of carnosine (beta- alanyl-1- histidine) on the wound healing in rats; Avaliação do efeito radioprotetor da carnosina (beta-alanil-1- histidina) no processo de cicatrização em ratos

Tanaka, Rosana Aramaki; Ramos, Flávia Maria de Moraes; Almeida, Solange Maria de; Vizioli, Mário Roberto; Bóscolo, Frab Norberto
Fonte: Universidade de São Paulo. Faculdade de Odontologia de Bauru Publicador: Universidade de São Paulo. Faculdade de Odontologia de Bauru
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; ; Formato: application/pdf
Publicado em 01/09/2005 ENG
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O objetivo deste estudo foi avaliar o efeito radioprotetor da carnosina (beta-alanil-1-histidina) no processo de cicatrização em ratos. Para isto, 48 ratos machos foram submetidos a um procedimento cirúrgico para realização de uma ferida retangular na região dorsal anterior. Os animais foram divididos aleatoriamente em 4 grupos experimentais: controle, irradiado, carnosina irradiado e carnosina. Os grupos carnosina e carnosina irradiado foram exposto a uma dose de corpo todo de 6 Gy de radiação gama, 72 horas após a cirurgia para confecção da ferida. O grupo carnosina e carnosina irradiado, adicionalmente, ao procedimento cirúrgico e a irradiação, receberam duas doses de solução aquosa de carnosina, a primeira sendo injetada 48 horas após a cirurgia, e a segunda 1 hora e 30 minutos antes da irradiação. A reparação tecidual nos 4 grupos foi avaliada 4, 7, 14 e 21 dias após a realização da ferida, por métodos morfológicos, histoquímicos e histofísicos. Em todos os períodos examinados, pode ser observado que os animais do grupo carnosina irradiado apresentaram um melhor desenvolvimento do tecido de granulação do que o grupo irradiado e muito similar ao do grupo controle. Logo, de acordo com as condições experimentais usadas...