Role of Aldose Reductase in the Metabolism and Detoxification of Carnosine-Acrolein Conjugates

Baba, Shahid P.; Hoetker, J. David; Merchant, Michael L.; Klein, Jon B.; Cai, Jian; Barski, Oleg A.; Conklin, Daniel J.; Bhatnagar, Aruni

doi:10.1074/jbc.m113.504753

Cited by 80 publications

(103 citation statements)

References 55 publications

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“…This beneficial effect can be explained in part by carnosine's physiological and biochemical properties (9). First, carnosine reduces glycoxidative stress, for example, by quenching reactive aldehydes and thereby preventing the formation of other reactive metabolites (3,4,11,16,24). Second, carnosine may increase insulin secretion in rodent diabetic models (27,34), thereby improving glycemic control in these animals.…”

mentioning

confidence: 99%

Aerobic and resistance training do not influence plasma carnosinase content or activity in type 2 diabetes

Stegen

Sigal

Kenny

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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A particular allele of the carnosinase gene (CNDP1) is associated with reduced plasma carnosinase activity and reduced risk for nephropathy in diabetic patients. On the one hand, animal and human data suggest that hyperglycemia increases plasma carnosinase activity. On the other hand, we recently reported lower carnosinase activity levels in elite athletes involved in high-intensity exercise compared with untrained controls. Therefore, this study investigates whether exercise training and the consequent reduction in hyperglycemia can suppress carnosinase activity and content in adults with type 2 diabetes. Plasma samples were taken from 243 males and females with type 2 diabetes (mean age = 54.3 yr, SD = 7.1) without major microvascular complications before and after a 6-mo exercise training program [4 groups: sedentary control ( n = 61), aerobic exercise ( n = 59), resistance exercise ( n = 63), and combined exercise training ( n = 60)]. Plasma carnosinase content and activity, hemoglobin (Hb) A1c, lipid profile, and blood pressure were measured. A 6-mo exercise training intervention, irrespective of training modality, did not decrease plasma carnosinase content or activity in type 2 diabetic patients. Plasma carnosinase content and activity showed a high interindividual but very low intraindividual variability over the 6-mo period. Age and sex, but not Hb A1c, were significantly related to the activity or content of this enzyme. It can be concluded that the beneficial effects of exercise training on the incidence of diabetic complications are probably not related to a lowering effect on plasma carnosinase content or activity.

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mentioning

confidence: 99%

Aerobic and resistance training do not influence plasma carnosinase content or activity in type 2 diabetes

Stegen

Sigal

Kenny

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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“…Similarly, carnosine treatment promotes recovery of cardiac function in isolated heart model of ischemia/ reperfusion [199,238]. Likewise, intraperitoneal administration of carnosine protected hearts from Adriamycin-induced cardiotoxicity and restored cardiac function after ischemia [239].…”

Section: Discussionmentioning

confidence: 99%

“…The filtrates were separated on HP 1100 LC connected to a Polar RP column using 5mM nonafluoropentanoic acid (NFPA) as the mobile phase. Detection of the carnosine aldehyde conjugates and their reduced forms was done on a Micromass Quattro LC/MS/MS system [199]. The ratio of peak intensity of conjugates and the internal standard was used for quantification.…”

Section: Discussionmentioning

confidence: 99%

“…Given the observation that Fe 2 chelators such as deferoxamine can increase HIF1-α levels and improve recovery from HLI [198] we rationalized that carnosine can increase revascularization in HLI through HIF1-α stabilization. Furthermore, our lab and others have shown that carnosine can form conjugates with lipid peroxidation products thereby limiting their reactivity [199]. Given the extensive evidence that supports a role of lipid peroxidation product in tissue injury associated with ischemia and recent evidence linking their levels to diminished progenitor cell levels and angiogenesis [142,192], we postulated that quenching of reactive aldehydes by carnosine could be beneficial in HLI.…”

Section: Project Objectivementioning

confidence: 99%

“…Hence, both pH buffering and calcium handling properties of carnosine are essential in regulating muscle contraction. In addition to pH buffering carnosine is known to exhibit antioxidant properties, [220] quench highly reactive carbonyl species [199,221] and chelate divalent metals such as Cu 2+ , Fe 2+ and Zn 2+ [196,197]. Carnosine also regulates neutrophil function, exhibits anti-aging and anti-inflammatory functions, regulates enzymes such as phosphorylase a, modulates gene transcription and possibly translation through regulation of eukaryotic initiation factor 4E protein [222][223][224].…”

Section: Introductionmentioning

confidence: 99%

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Carnosine, a therapeutic potential for critical limb ischemic.

Boakye¹

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Carnoquinolines Target Copper Dyshomeostasis, Aberrant Protein–Protein Interactions, and Oxidative Stress

Bellia

Grasso

Ahmed

et al. 2020

Chemistry A European J

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Metal dysregulation, oxidative stress, protein modification, and aggregation are factors strictly interrelated and associated with neurodegenerative pathologies. As such, all of these aspects represent valid targets to counteract neurodegeneration and, therefore, the development of metal‐binding compounds with other properties to combat multifactorial disorders is definitely on the rise. Herein, the synthesis and in‐depth analysis of the first hybrids of carnosine and 8‐hydroxyquinoline, carnoquinolines (CarHQs), which combine the properties of the dipeptide with those of 8‐hydroxyquinoline, are reported. CarHQs and their copper complexes were characterized through several techniques, such as ESI‐MS and NMR, UV/Vis, and circular dichroism spectroscopy. CarHQs can modulate self‐ and copper‐induced amyloid‐β aggregation. These hybrids combine the antioxidant activity of their parent compounds. Therefore, they can simultaneously scavenge free radicals and reactive carbonyl species, thanks to the phenolic group and imidazole ring. These results indicate that CarHQs are promising multifunctional candidates for neurodegenerative disorders and they are worthy of further studies.

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Role of Aldose Reductase in the Metabolism and Detoxification of Carnosine-Acrolein Conjugates

Cited by 80 publications

References 55 publications

Aerobic and resistance training do not influence plasma carnosinase content or activity in type 2 diabetes

Aerobic and resistance training do not influence plasma carnosinase content or activity in type 2 diabetes

Carnosine, a therapeutic potential for critical limb ischemic.

Carnoquinolines Target Copper Dyshomeostasis, Aberrant Protein–Protein Interactions, and Oxidative Stress

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