Predictors of Change in Plasma Total Cysteine: Longitudinal Findings from the Hordaland Homocysteine Study

El-Khairy, Lina; Vollset, Stein Emil; Refsum, Helga; Ueland, Per Magne

doi:10.1373/49.1.113

Cited by 45 publications

(34 citation statements)

References 24 publications

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“…For instance, a study has shown that NAC can improve wound healing in alloxan-induced diabetic mice via clearance of free oxygen radicals [14]. In contrast, we notice in some other papers that the levels of plasma total cysteine correlates positively with the obesity or fat mass of patients [15-17]. A recent study suggested that the increased concentration of L-cysteine can inhibit insulin secretion from pancreatic β-cells through binding and inactivation of pyruvate kinase muscle isoform 2 [18].…”

Section: Introductionmentioning

confidence: 97%

Inhibition of Methylglyoxal-Induced AGEs/RAGE Expression Contributes to Dermal Protection by N-Acetyl-L-Cysteine

Liu¹,

Meng²,

Chen³

et al. 2017

Cell Physiol Biochem

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Background/Aim: Accumulation of advanced glycation end products (AGEs) is a major cause of diabetes mellitus (DM) skin complications. Methylglyoxal (MGO), a reactive dicarbonyl compound, is a crucial intermediate of AGEs generation. N-acetyl-L-cysteine (NAC), an active ingredient of some medicines, can induce endogenous GSH and hydrogen sulfide generation, and set off a condensation reaction with MGO. However, there is rare evidence to show NAC can alleviate DM-induced skin injury through inhibition of AGEs generation or toxicity. The present study aimed to observe the effects of NAC on MGO-induced inflammatory injury and investigate the roles of AGEs and its receptor (RAGE) in NAC’s dermal protection in human HaCaT keratinocytes. Methods: The cells were exposed to MGO to simulate a high MGO status in diabetic blood or tissues. The content of AGEs in serum or cell medium was measured with ELISA. The protective effects of NAC against MGO-induce injury were evaluated by administration before MGO one hour, in virtue of cell viability, mitochondrial membrane potential, inflammation reaction, nuclear factor (NF)-κB activation, matrix metalloproteinase (MMP)-9 expression, as well as cellular behavioral function. Results: We found the AGEs levels of patients with DM were elevated comparing with healthy volunteers. The in vitro AGEs generation was also able to be enhanced by the exposure of HaCaT cells to MGO, which reduced dose-dependently cellular viability, damaged mitochondrial function, triggered secretion of interleukin (IL)-6 and IL-8, activated NF-κB and upregulated MMP-9 expression. Furthermore, the exposure caused cellular adhesion and migration dysfunction, as well as collagen type I inhibition. Importantly, before the exposure to MGO, the preconditioning with NAC significantly attenuated MGO-induced AGEs generation, improved cellular viability and mitochondrial function, partially reversed the overexpression of proinflammatory factors and MMP-9, as well as the activation of NF-κB. Lastly, NAC blocked MGO-induced RAGE upregulation, and inhibition of RAGE with its neutralizing antibody significantly alleviated MGO-induced NF-κB activation, MMP-9 upregulation and inflammatory injury in HaCaT cells. Conclusion: The present work indicates the administration of NAC can prevent MGO-induced dermal inflammatory injury through inhibition of AGEs/RAGE signal, which may provide a basal support for the treatment of diabetic skin complications with NAC-containing medicines in the future.

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Section: Introductionmentioning

confidence: 97%

Inhibition of Methylglyoxal-Induced AGEs/RAGE Expression Contributes to Dermal Protection by N-Acetyl-L-Cysteine

Liu¹,

Meng²,

Chen³

et al. 2017

Cell Physiol Biochem

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“…The inhibitory actions of cysteine were originally studied with incubations of mM concentrations of the amino acid with catalase [2,3,19]. These conditions are not representative of the physiological levels of this amino acid, which are normally in the M range, and the observed inhibition is unlikely to occur naturally [20].…”

Section: Introductionmentioning

confidence: 99%

Homocysteine Inhibits Hydrogen Peroxide Breakdown by Catalase

Milton¹

2008

TOEIJ

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Catalase, an antioxidant enzyme responsible for degradation of hydrogen peroxide, is protective in many diseases. The amino-acid homocysteine has been suggested to be a pro-oxidant with elevated levels linked to the oxidative stress seen in Alzheimer's and other diseases. This study shows that homocysteine inhibits the breakdown of hydrogen peroxide by catalase. Physiological concentrations of homocysteine inhibited catalase breakdown of hydrogen peroxide. The inhibition of catalase was by generation of the inactive catalase compound II and prevented by ethanol or NADPH but unaffected by iron. Physiological concentrations of homocysteine also inhibited cellular catalase but were not cytotoxic. homocysteine enhanced the toxicity of the amyloid-ß peptide in an in vitro model of Alzheimer's neurodegeneration. The antioxidant vitamin E blocked the toxicity of amyloid-ß plus homocysteine but not the catalase inhibition. Catalase inhibition by homocysteine may increase the levels of hydrogen peroxide and play a role in the pathology of disease.

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“…Second, unless perturbed nutritionally, Hcy concentrations change relatively little over a 5-year period. 22,23 The elevated Hcy concentration found at diagnosis was most likely a chronic condition. Consequently, the vascular damage associated with elevated Hcy potentially occurred over a period of many years.…”

Section: +mentioning

confidence: 99%

Elevated Homocysteine Concentrations Decrease the Antihypertensive Effect of Angiotensin-Converting Enzyme Inhibitors in Hypertensive Patients

Sun

Wang

et al. 2017

ATVB

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Objective— We aimed to examine whether baseline homocysteine (Hcy) concentrations affect antihypertensive responses to enalapril treatment among previously untreated hypertensive patients (n=10 783) in the CSPPT (China Stroke Primary Prevention Trial). Approach and Results— After a 3-week run-in treatment with a daily dose of 10 mg enalapril, eligible hypertensive patients were randomly assigned to a double-blind daily treatment of a tablet of either enalapril (10 mg) and folic acid (0.8 mg) or enalapril (10 mg) alone for a median of 4.5 years. After the 3-week treatment period with enalapril alone, the systolic blood pressure–lowering effect was significantly reduced by 1.39 (95% confidence interval 0.40–2.37) and 3.25 (95% confidence interval 1.98–4.52) mm Hg, respectively, in those with baseline Hcy concentrations of 10 to 15 and ≥15 μmol/L ( P for trend <0.001) as compared with those with Hcy concentration of <10 μmol/L. Similar results were observed after a 15-week treatment period with enalapril alone. After a median 4.5-year enalapril-based antihypertensive treatment period, compared with those with Hcy concentration of <10 μmol/L, the systolic blood pressure–lowering effect was still significantly reduced by 0.77 (95% confidence interval 0.01–1.53) and 1.70 (95% confidence interval 0.72–2.68) mm Hg, respectively, in those with Hcy concentrations of 10 to 15 and ≥15 μmol/L ( P for trend <0.001). In addition, participants with higher baseline Hcy concentrations had persistently higher systolic blood pressure levels across the entire study treatment period. Similarly, baseline Hcy concentrations were inversely associated with diastolic blood pressure reduction during the short-term enalapril alone treatment. However, the inverse association between baseline Hcy and diastolic blood pressure reduction was attenuated and became insignificant after the long-term enalapril-based treatment period. Conclusions— Elevated Hcy concentrations significantly decreased the antihypertensive effect of the short-term and long-term enalapril-based antihypertensive treatment in previously untreated hypertensive patients.

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Predictors of Change in Plasma Total Cysteine: Longitudinal Findings from the Hordaland Homocysteine Study

Cited by 45 publications

References 24 publications

Inhibition of Methylglyoxal-Induced AGEs/RAGE Expression Contributes to Dermal Protection by N-Acetyl-L-Cysteine

Inhibition of Methylglyoxal-Induced AGEs/RAGE Expression Contributes to Dermal Protection by N-Acetyl-L-Cysteine

Homocysteine Inhibits Hydrogen Peroxide Breakdown by Catalase

Elevated Homocysteine Concentrations Decrease the Antihypertensive Effect of Angiotensin-Converting Enzyme Inhibitors in Hypertensive Patients

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