Can <scp>l</scp>-Cysteine and Vitamin D Rescue Vitamin D and Vitamin D Binding Protein Levels in Blood Plasma of African American Type 2 Diabetic Patients?

Jain, Sushil K.; Kahlon, Gunjan; Bass, Pat F.; Levine, Steven N.; Warden, Cassandra

doi:10.1089/ars.2015.6320

Cited by 29 publications

(41 citation statements)

References 10 publications

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“…In chemistry, NAC is derived from L-cysteine, whose amino-group is acetylated. It was reported that L-cysteine, as well as its metabolite H 2 S, is decreased in African Americans with Type 2 DM [11, 12]. Another report suggested that NAC can react with MGO to produce N-α-acetyl-S-(1-hydroxy-2-oxo-prop-1-yl)cysteine [13].…”

Section: Introductionmentioning

confidence: 99%

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: 99%

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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“…Consistently, it has been pointed out that positive link between plasma levels of VDBP and 25(OH)D and those of GSH; specifically, lower plasma levels of VDBP and 25(OH)D correlated with lower GSH level, and increases in GSH level upregulated 25(OH)D and VDBP status in Zucker diabetic fatty rats . Supplementation of GSH could raise blood levels of VDBP and vitamin in African‐American patients with type 2 diabetes . Another study also suggested a significant positive correlation between GSH level and blood levels of L‐cysteine (LC) and vitamin D in type 2 diabetic patients .…”

Section: Discussionmentioning

confidence: 96%

Plasma VDBP, 25(OH)D, and GSH levels predict surgical outcome in patients with cervical spondylotic myelopathy

Peng

Zhan

Liu

et al. 2019

The Kaohsiung J of Med Scie

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This study intends to investigate the predictive values of plasma Vitamin D‐binding protein (VDBP), 25‐hydroxyvitamin D [25(OH)D], and glutathione (GSH) levels in the outcome of cervical spondylotic myelopathy (CSM) surgery. Surgery outcomes of 236 CSM patients were determined. Recovery rate was calculated according to Japanese Orthopaedic Association (JOA) scores during follow‐up. CSM patients with a recovery rate >50% were assigned with good prognosis and the rest were with fair prognosis. Preoperative and postoperative neurologic function scores were compared among groups. Plasma VDBP and 25(OH)D levels, as well as GSH levels were measured by ELISA and glutathione reductase recycling assay, respectively. Pearson's correlation coefficient was performed to analyze the correlation among plasma VDBP, 25(OH)D, and GSH levels. Receiver operating characteristic (ROC) curve was applied to evaluate the predictive value of plasma VDBP, 25(OH)D, and GSH levels for surgical outcome. Logistic regression model was used to analyze risk factors for surgical outcome. Compared with those with fair prognosis, CSM patients with good prognosis group exhibited higher postoperative neurologic function scores, plasma VDBP, 25(OH)D, and GSH levels, and better improvements in spinal cord compression and motions of the cervical vertebra. Plasma VDBP, 25(OH)D, and GSH levels were favorable prognostic factors for CSM surgical outcome. The sensitivity and specificity of plasma VDBP, plasma 25(OH)D, and plasma GSH were 89.8% and 91.7%, 85.8% and 84.4%, and 79.5% and 91.7%, respectively. Our study provides evidence that higher plasma VDBP, 25(OH)D, and GSH levels may predict better surgical outcome in CSM patients.

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“…Previous studies in the literature report lower blood levels of VDBP, 25(OH) vitamin D, LC, and GSH in diabetes . GSH is a physiological antioxidant, a co‐factor of many enzymes, and plays an important role in a multitude of cellular processes.…”

Section: Discussionmentioning

confidence: 99%

“…Epidimiological studies demonstrate that higher rates of deficiency of 25‐hydroxy‐vitamin D could be linked to the prevalence of several chronic diseases, including diabetes . Previous studies have reported an association between lower blood levels of 25(OH) vitamin D, VDBP, and GSH in diabetic patients, and in African‐American subjects .…”

Section: Introductionmentioning

confidence: 99%

“…Vitamin D binding protein (VDBP) is a main transporter of vitamin D and 25(OH) vitamin D . Recent studies suggest that blood concentrations of VDBP are positively related to the half‐life of circulating 25(OH) vitamin D , and that blood levels of GSH have a positive relationship with those of VDBP and 25(OH) vitamin D in the blood of African‐American type 2 diabetic patients . L‐cysteine is a rate limiting precursor of GSH biosynthesis .…”

Section: Introductionmentioning

confidence: 99%

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L‐cysteine supplementation upregulates glutathione (GSH) and vitamin D binding protein (VDBP) in hepatocytes cultured in high glucose and in vivo in liver, and increases blood levels of GSH, VDBP, and 25‐hydroxy‐vitamin D in Zucker diabetic fatty rats

Jain

Marie

Warden

et al. 2016

Molecular Nutrition Food Res

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ScopeVitamin D binding protein (VDBP) status has an effect on and can potentially improve the status of 25(OH) vitamin D and increase the metabolic actions of 25(OH) vitamin D under physiological and pathological conditions. Diabetes is associated with lower levels of glutathione (GSH) and 25(OH) vitamin D. This study examined the hypothesis that upregulation of GSH will also upregulate blood levels of VDBP and 25(OH) vitamin D in type 2 diabetic rats.Methods and resultsL‐cysteine (LC) supplementation was used to upregulate GSH status in a FL83B hepatocyte cell culture model and in vivo using Zucker diabetic fatty (ZDF) rats. Results show that LC supplementation upregulates both protein and mRNA expression of VDBP and vitamin D receptor (VDR) and GSH status in hepatocytes exposed to high glucose, and that GSH deficiency, induced by glutamate cysteine ligase knockdown, resulted in the downregulation of GSH, VDBP, and VDR and an increase in oxidative stress levels in hepatocytes. In vivo, LC supplementation increased GSH and protein and mRNA expression of VDBP and vitamin D 25‐hydroxylase (CYP2R1) in the liver, and simultaneously resulted in elevated blood levels of LC and GSH, as well as increases in VDBP and 25(OH) vitamin D levels, and decreased inflammatory biomarkers in ZDF rats compared with those in placebo‐supplemented ZDF rats consuming a similar diet.ConclusionLC supplementation may provide a novel approach by which to raise blood levels of VDBP and 25(OH) vitamin D in type 2 diabetes.

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Can l-Cysteine and Vitamin D Rescue Vitamin D and Vitamin D Binding Protein Levels in Blood Plasma of African American Type 2 Diabetic Patients?

Cited by 29 publications

References 10 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

Plasma VDBP, 25(OH)D, and GSH levels predict surgical outcome in patients with cervical spondylotic myelopathy

L‐cysteine supplementation upregulates glutathione (GSH) and vitamin D binding protein (VDBP) in hepatocytes cultured in high glucose and in vivo in liver, and increases blood levels of GSH, VDBP, and 25‐hydroxy‐vitamin D in Zucker diabetic fatty rats

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