Carnosine disaggregates glycated α-crystallin: an in vitro study

Seidler, Norbert W.; Yeargans, George S; Morgan, Timothy G

doi:10.1016/j.abb.2004.04.024

Cited by 73 publications

(32 citation statements)

References 38 publications

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“…This process has been termed by Hipkiss et al [30] as ‘carnosinylation’ of protein. Not only was carnosinylation of protein proposed as a mode of protection from glycation, but also to help cells in tagging glycated proteins for proteolysis and removal [31]. This mechanism extends carnosine’s desirable effects to include a possible mode of treatment of a preexisting state of glycation in cells.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, carnosine is superior to other known antiglycation substances which exert their effect mostly via interaction with reactive aldehydes. Carnosine’s superiority comes from the fact that it acts at levels of the prevention of AGEs formation, the intervention with formed AGE, and retards any further glycation and the more striking feature of the ability to reverse preformed AGEs [28,29,30,31]. Moreover, carnosine has been documented as one of the least known toxic substances and suggested as a reservoir of histidine that protects from its toxicity [19, 30].…”

Section: Introductionmentioning

confidence: 99%

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Antiglycation and Antioxidant Effect of Carnosine against Glucose Degradation Products in Peritoneal Mesothelial Cells

Alhamdani

Al-Kassir²,

Abbas³

et al. 2007

Nephron Clin Pract

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Background/Aim:Toxicity with advanced glycation end products (AGEs) is a major problem in uremic patients. Treatment with peritoneal dialysis (PD) exacerbates AGE formation as a result of bioincompatibility of the conventional peritoneal dialysis fluid (PDF). The presence of glucose degradation products (GDPs) in PDF is the main cause of its bioincompatibility. Carnosine is an endogenous dipeptide with a powerful antiglycation/antioxidant activity. In an attempt to improve PDF biocompatibility, we evaluated the effect of carnosine in human peritoneal mesothelial cells (HPMC) incubated with PDF or GDPs in vitro. Methods: HPMC were incubated for short or prolonged time with PDF in the presence or absence of carnosine. Similarly, HPMC were incubated in the same condition but with a combination of GDPs. Following the incubation, cells were tested for their viability, protein carbonyl content and reactive oxygen species (ROS) production. Results: Results demonstrated a significant protective effect of carnosine to HPMC in both acute and chronic conditions with PDF or GDPs as judged by the enhancement of cell viability, preserved protein from modification and decreased ROS production. Conclusion: Carnosine enhanced HPMC viability against the toxic effect of GDPs probably through protection of cellular protein from modification and from ROS-mediated oxidative damage. The salutary effect of carnosine may render it a desirable candidate for improving PDF biocompatibility and reducing AGE complications in PD patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antiglycation and Antioxidant Effect of Carnosine against Glucose Degradation Products in Peritoneal Mesothelial Cells

Alhamdani

Al-Kassir²,

Abbas³

et al. 2007

Nephron Clin Pract

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show abstract

“…Properties pertaining to the physiological roles of carnosine include its pH-buffering capacity, scavenging of reactive oxygen species (ROS) and peroxyl radicals, metal-ion chelation and protection against advanced glycation and lipoxidation end products (AGE and ALE, Boldyrev et al 2013). Notably, carnosine has also been demonstrated to reverse pre-formed glycated proteins (Seidler et al 2004). In line with its role in muscle physiology, food supplements containing carnosine or its precursor beta-alanine improve exercise performance in untrained individuals (Hill et al 2007) as well as in elite athletes (Van Thienen et al 2009;Baguet et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Identification and characterisation of carnostatine (SAN9812), a potent and selective carnosinase (CN1) inhibitor with in vivo activity

et al. 2018

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Carnosinase 1 (CN1) has been postulated to be a susceptibility factor for developing diabetic nephropathy (DN). Although its major substrate, carnosine, is beneficial in rodent models of DN, translation of these findings to humans has been hampered by high CN1 activity in human serum resulting in rapid degradation of carnosine. To overcome this hurdle, we screened a protease-directed small-molecule library for inhibitors of human recombinant CN1. We identified SAN9812 as a potent and highly selective inhibitor of CN1 activity with a K i of 11 nM. It also inhibited CN1 activity in human serum and serum of transgenic mice-overexpressing human CN1. Subcutaneous administration of 30 mg/kg SAN9812 led to a sustained reduction in circulating CN1 activity in human CN1 transgenic (TG) mice. Simultaneous administration of carnosine and SAN9812 increased carnosine levels in plasma and kidney by up to 100-fold compared to treatment-naïve CN1-overexpressing mice. To our knowledge, this is the first study reporting on a potent and selective CN1 inhibitor with in vivo activity. SAN9812, also called carnostatine, may be used to increase renal carnosine concentration as a potential therapeutic modality for renal diseases linked to glycoxidative conditions.

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“…Treatment of H 2 O 2 -incubated lens with L-carnitine decreased PTMs induced by oxidative stress and safeguarded a-crystallin chaperone activity (94). Carnosine, a naturally occurring dipeptide (b-alanyl-L-histidine), was shown to induce the disaggregation of glycated acrystallin and contribute to the controlled unfolding of glycated protein (102). In another study, it was shown that carnosine prevented the fructose-induced crosslinking of a-crystallin in doseand time-dependent manner, there by prevented the loss of acrystallin chaperone activity (103).…”

Section: Modulation Of A-crystallin Chaperone Activity By Antiglycatimentioning

confidence: 99%

Modulation of α‐crystallin chaperone activity: A target to prevent or delay cataract?

Pasupulati

Reddy

2009

IUBMB Life

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SummaryCataract, loss of eye lens transparency, is the leading cause of blindness worldwide. a-Crystallin, initially known as one of the major structural proteins of the eye lens, is composed of two homologous subunits aA-and aB-crystallins. It is convincingly established now that a-crystallin functions like a chaperone and plays a decisive role in the maintenance of eye lens transparency. The functional ability of a-crystallin subunits is to act in cooperation as molecular chaperones to prevent the cellular aggregation and/or inactivation of client proteins under variety of stress conditions. However, chaperone-like activity of a-crystallin could be deteriorated or lost during aging or under certain clinical conditions because of various genetic and environmental factors. This review will focus specifically on relevance of a-crystallin chaperone function to lens transparency. In particular, we reviewed the studies that demonstrate the modulation of a-crystallin chaperone-like activity and discussed the possibility of chaperone-like activity of a-crystallin as a potential target to prevent or delay the cataractogenesis.2009 IUBMB IUBMB Life, 61(5): [485][486][487][488][489][490][491][492][493][494][495] 2009

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Carnosine disaggregates glycated α-crystallin: an in vitro study

Cited by 73 publications

References 38 publications

Antiglycation and Antioxidant Effect of Carnosine against Glucose Degradation Products in Peritoneal Mesothelial Cells

Antiglycation and Antioxidant Effect of Carnosine against Glucose Degradation Products in Peritoneal Mesothelial Cells

Identification and characterisation of carnostatine (SAN9812), a potent and selective carnosinase (CN1) inhibitor with in vivo activity

Modulation of α‐crystallin chaperone activity: A target to prevent or delay cataract?

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