LC–ESI-MS/MS determination of 4-hydroxy-trans-2-nonenal Michael adducts with cysteine and histidine-containing peptides as early markers of oxidative stress in excitable tissues

Orioli, Marica; Aldini, Giancarlo; Beretta, Giangiacomo; Facino, Roberto Maffei

doi:10.1016/j.jchromb.2005.04.025

Cited by 74 publications

(73 citation statements)

References 21 publications

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“…Analyses of plasma carnosine of one subject were performed using a validated liquid chromatography (LC)-electrospray ionization (EIS)/multistage mass spectrometry (LC-ESI-MS/MS) method (26). Briefly, aliquots of 100 l EDTA-plasma samples were spiked with H-Tyr-His-OH as an internal standard (final concentration: 20 M), deproteinized by perchloric acid (final concentration: 700 mM) and centrifuged at 18,000 rpm for 10 min.…”

Section: Methodsmentioning

confidence: 99%

“…1B) and the peak of ␤-alanine (the product of the carnosinase reaction) increased, which illustrates that the peak at 15.6 min genuinely represents carnosine. Plasma samples of one subject were analysed by an independent laboratory with the LC-ESI-MS/MS method (26), and carnosine was detected at 30 min (11.8 M) and 45 min (3.4 M) after carnosine supplementation (4 g), whereas at the other time points no carnosine could be detected.…”

Section: Carnosine Is Detectable In Human Plasma By Hplcmentioning

confidence: 99%

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Low plasma carnosinase activity promotes carnosinemia after carnosine ingestion in humans

Everaert

Taes

Heer

et al. 2012

American Journal of Physiology-Renal Physiology

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A polymorphism in the carnosine dipeptidase-1 gene (CNDP1), resulting in decreased plasma carnosinase activity, is associated with a reduced risk for diabetic nephropathy. Because carnosine, a natural scavenger/suppressor of ROS, advanced glycation end products, and reactive aldehydes, is readily degraded in blood by the highly active carnosinase enzyme, it has been postulated that low serum carnosinase activity might be advantageous to reduce diabetic complications. The aim of this study was to examine whether low carnosinase activity promotes circulating carnosine levels after carnosine supplementation in humans. Blood and urine were sampled in 25 healthy subjects after acute supplementation with 60 mg/kg body wt carnosine. Precooled EDTA-containing tubes were used for blood withdrawal, and plasma samples were immediately deproteinized and analyzed for carnosine and beta-alanine by HPLC. CNDP1 genotype, baseline plasma carnosinase activity, and protein content were assessed. Upon carnosine ingestion, 8 of the 25 subjects (responders) displayed a measurable increase in plasma carnosine up to 1 h after supplementation. Subjects with no measurable increment in plasma carnosine (nonresponders) had approx. 2-fold higher plasma carnosinase protein content and approx. 1.5-fold higher activity compared with responders. Urinary carnosine recovery was 2.6-fold higher in responders versus nonresponders and was negatively dependent on both the activity and protein content of the plasma carnosinase enzyme. In conclusion, low plasma carnosinase activity promotes the presence of circulating carnosine upon an oral challenge. These data may further clarify the link among CNDP1 genotype, carnosinase, and diabetic nephropathy

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Section: Methodsmentioning

confidence: 99%

Section: Carnosine Is Detectable In Human Plasma By Hplcmentioning

confidence: 99%

Low plasma carnosinase activity promotes carnosinemia after carnosine ingestion in humans

Everaert

Taes

Heer

et al. 2012

American Journal of Physiology-Renal Physiology

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“…Carnosine's ability to react with MG and protect proteins against MG-induced damage may contribute to the dipeptide's apparent anti-ageing activity (Hipkiss, 2007b). The presence of carnosine-aldehyde adducts in muscle and urine (Orioli et al, 2005(Orioli et al, & 2007 provides evidence for the occurrence in vivo of at least some of carnosine's putative aldehyde-scavenging actions. It should be pointed out that while no protein-carnosine adducts have been detected in vivo, NMR data has indicated the presence of carnosine-phosphatidylcholine adducts in human leg muscle, possibly arising from oxidation of amino lipids and their subsequent reaction with the dipeptide (Schroder et al, 2004).…”

Section: Carnosine and Post-synthetic Protein Modificationmentioning

confidence: 99%

On the enigma of carnosine’s anti-ageing actions

Hipkiss¹

2009

Experimental Gerontology

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Carnosine ( -alanyl-L-histidine) has described as a forgotten and enigmatic dipeptide. Carnosine's enigma is particularly exemplified by its apparent anti-ageing actions; it suppresses cultured human fibroblast senescence and delays ageing in senescence-accelerated mice and Drosophila, but the mechanisms reponsible remain uncertain. In addition to carnosine's well-documented anti-oxidant, anti-glycating, aldehyde-scavenging and toxic metal-ion chelating properties, its ability to influence the metabolism of altered polypeptides, whose accumulation characterises the senescent phenotype, should also be considered. When added to cultured cells, carnosine was found in a recent study to suppress phosphorylation of the translational initiation factor eIF4E resulting in decreased translation frequency of certain mRNA species. Mutations in the gene coding for eIF4E in nemtodes extend organism lifespan, hence carnosine's anti-ageing effects may be a consequence of decreased error-protein synthesis which in turn lowers formation of protein carbonyls and increases protease availability for degradation of polypeptides altered postsynthetically. Other studies have revealed carnosine-induced upregulation of stress protein expression and nitric oxide synthesis, both of which may stimulate proteasomal elimination of altered proteins. Some anti-convulsants can enhance nematode longevity and suppress the effects of a protein repair defect in mice, and as carnosine exerts anti-convulsant effects in rodents, it is speculated that the dipeptide may participate in the repair of protein isoaspartyl groups. These new observations only add to the enigma of carnosine's real in vivo functions. More experimentation is clearly required. ACCEPTED MANUSCRIPT 3 Carnosine and ageing.The naturally-occurring dipeptide carnosine ( -alanyl-L-histidine) has been described as forgotten and enigmatic (Bauer, 2005): the present paper is an attempt to rectify the former opinion, but, however only adds to the latter view. Amongst carnosine's enigmatic properties are its apparent anti-ageing actions; the dipeptide is one of a very few naturally-occurring compounds which suppresses cell senescence, induces rejuvenating effects Holliday, 1994 and, and protects against telomere shortening (Shao et al., 2004) in cultured human fibroblasts. The dipeptide also extends the life-span of senescence-accelerated mice (Yuneva et al., 1999) and Drosophila (Yuneva et al., 2002). There are many possible mechanisms by which carnosine exerts these anti-ageing actions however, some of which were summarized a decade ago (Hipkiss, 1998). Meanwhile there have been a number of publications suggesting further possible routes by which carnosine could suppress

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“…Carnosine can inhibit many deleterious biochemical phenomena thought to be associated with generation of the aged phenotype, these include protein damage (including cross-linking [13]) induced by reactive oxygen species [14], reactive nitrogen species [15,16], reducing sugars [13] and reactive carbonyl species such as malondialdehyde [17], 4-hydroxynonenal [18,19] and methylglyoxal [20]. Model animal studies show beneficial effects of the dipeptide towards a number of age-related physiological conditions including impaired wound healing [21,22], Alzheimer's disease [23,24], Parkinson's disease [25,26], stroke [27,28], atherosclerosis [29,30], cataracts [31,32] and diabetic kidney disease [33,34].…”

Section: Carnosine and Agingmentioning

confidence: 99%

Possible Benefit of Dietary Carnosine towards Depressive Disorders

Hipkiss¹

2014

aging dis

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Many stress-related and depressive disorders have been shown to be associated with one or more of the following; shortened telomeres, raised cortisol levels and increased susceptibility to age-related dysfunction. It is suggested here that insufficient availability of the neurological peptide, carnosine, may provide a biochemical link between stress-and depression-associated phenomena: there is evidence that carnosine can enhance cortisol metabolism, suppress telomere shortening and exert anti-aging activity in model systems. Dietary supplementation with carnosine has been shown to suppress stress in animals, and improve behaviour, cognition and well-being in human subjects. It is therefore proposed that the therapeutic potential of carnosine dietary supplementation towards stress-related and depressive disorders should be examined.Key words: carnosine, telomeres, human, diet, supplementation, depression, cognition, stress, cortisol, aging A recent paper [1] has shown that supplementation of human diets with carnosine (β-alanyl-L-histidine), a naturally-occurring neurobiological peptide, can provoke beneficial effects on exercise performance and quality of life. Another recent paper [2] has shown that major depressive disorder (MDD) is associated with reduced telomere length, increased susceptibility towards agerelated dysfunction and raised cortisol levels in response to stress, while two other recent papers have described an association between decreased leukocyte telomere length and stress-associated disorders [3,4]. It is objective of the present communication to suggest that (i) carnosine insufficiency could provide a link between stress and depression-associated phenomena and age-related dysfunction, and (ii) carnosine may possess therapeutic potential towards depression and stress-associated disorders when administered as a dietary supplement. Carnosine and agingCarnosine is a normal constituent of brain and muscle. In the brain carnosine is synthesized by and secreted from astrocytes: it is degraded to its constituent amino acids by either cellular carnosinase (CNDP1) or serum carnosinase (CNDP2), whose activities in the brain possibly increase in old age [5]. Carnosine and related peptides such as anserine and balenine can also be obtained via carnivorous diets but are absent from strict vegetarian diets.Although characterized more than a century ago [6], the "true" function of carnosine remains elusive, thus the dipeptide has been described as enigmatic [7]. Evidence from animal and model studies suggests that carnosine is multifunctional. Cell culture studies show that carnosine can inhibit growth of transformed cells [8][9][10], delay

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LC–ESI-MS/MS determination of 4-hydroxy-trans-2-nonenal Michael adducts with cysteine and histidine-containing peptides as early markers of oxidative stress in excitable tissues

Cited by 74 publications

References 21 publications

Low plasma carnosinase activity promotes carnosinemia after carnosine ingestion in humans

Low plasma carnosinase activity promotes carnosinemia after carnosine ingestion in humans

On the enigma of carnosine’s anti-ageing actions

Possible Benefit of Dietary Carnosine towards Depressive Disorders

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