Dataset Information

Vitamin D status is independently associated with plasma glutathione and cysteine thiol/disulphide redox status in adults.

ABSTRACT: Redox status and inflammation are important in the pathophysiology of numerous chronic diseases. Epidemiological studies have linked vitamin D status to a number of chronic diseases. We aimed to examine the relationships between serum 25-hydroxyvitamin D [25(OH)D] and circulating thiol/disulphide redox status and biomarkers of inflammation.This was a cross-sectional study of N = 693 adults (449 females, 244 males) in an apparently healthy, working cohort in Atlanta, GA. Plasma glutathione (GSH), cysteine (Cys) and their associated disulphides were determined with high-performance liquid chromatography, and their redox potentials (Eh GSSG and Eh CySS) were calculated using the Nernst equation. Serum inflammatory markers included interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-?, assayed on a multiplex platform, and C-reactive protein (CRP), assayed commercially. Relationships were assessed with multiple linear regression analyses.Serum 25(OH)D was positively associated with plasma GSH (? ± SE: 0·002 ± 0·0004) and negatively associated with plasma Eh GSSG (? ± SE: -0·06 ± 0·01) and Cys (? ± SE: -0·01 ± 0·003) (P < 0·001 for all); statistical significance remained after adjusting for age, gender, race, percentage body fat and traditional cardiovascular risk factors (P = 0·01-0·02). The inverse relationship between serum 25(OH)D and CRP was confounded by percentage body fat, and full adjustment for covariates attenuated serum 25(OH)D relationships with other inflammatory markers to nonstatistical significance.Serum 25(OH)D concentrations were independently associated with major plasma thiol/disulphide redox systems, suggesting that vitamin D status may be involved in redox-mediated pathophysiology.

SUBMITTER: Alvarez JA

PROVIDER: S-EPMC4115025 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Vitamin D status is independently associated with plasma glutathione and cysteine thiol/disulphide redox status in adults.

Alvarez Jessica A JA Chowdhury Ritam R Jones Dean P DP Martin Greg S GS Brigham Kenneth L KL Binongo José N JN Ziegler Thomas R TR Tangpricha Vin V

Clinical endocrinology 20140415 3

<h4>Objective</h4>Redox status and inflammation are important in the pathophysiology of numerous chronic diseases. Epidemiological studies have linked vitamin D status to a number of chronic diseases. We aimed to examine the relationships between serum 25-hydroxyvitamin D [25(OH)D] and circulating thiol/disulphide redox status and biomarkers of inflammation.<h4>Design</h4>This was a cross-sectional study of N = 693 adults (449 females, 244 males) in an apparently healthy, working cohort in Atlan ...[more]

PMID: 24628365

Similar Datasets

Project description:Background:Both systemic redox status and diet quality are associated with risk outcomes in chronic disease. It is not known, however, the extent to which diet quality influences plasma thiol/disulfide redox status. Objective:The purpose of this study was to investigate the influence of diet, as measured by diet quality scores and other dietary factors, on systemic thiol/disulfide redox status. Methods:We performed a cross-sectional study of 685 working men and women (ages ?18 y) in Atlanta, GA. Diet was assessed by 3 diet quality scores: the Alternative Healthy Eating Index (AHEI), Dietary Approaches to Stop Hypertension (DASH), and the Mediterranean Diet Score (MDS). We measured concentrations of plasma glutathione (GSH), cysteine, their associated oxidized forms [glutathione disulfide (GSSG) and cystine (CySS), respectively], and their redox potentials (EhGSSG and EhCySS) to determine thiol/disulfide redox status. Linear regression modeling was performed to assess relations between diet and plasma redox after adjustment for age, body mass index (BMI), sex, race, and history of chronic disease. Results:MDS was positively associated with plasma GSH (? = 0.02; 95% CI: 0.003, 0.03) and total GSH (GSH + GSSG) (? = 0.02; 95% CI: 0.003, 0.03), and inversely associated with the CySS:GSH ratio (? = -0.02; 95% CI: -0.04, -0.004). There were significant independent associations between individual MDS components (dairy, vegetables, fish, and monounsaturated fat intake) and varying plasma redox indexes (P < 0.05). AHEI and DASH diet quality indexes and other diet factors of interest were not significantly correlated with plasma thiol and disulfide redox measures. Conclusion:Adherence to the Mediterranean diet was significantly associated with a favorable plasma thiol/disulfide redox profile, independent of BMI, in a generally healthy working adult population. Although longitudinal studies are warranted, these findings contribute to the feasibility of targeting a Mediterranean diet to improve plasma redox status.

Project description:Cysteine is susceptible to a variety of modifications by reactive oxygen and nitrogen oxide species, including glutathionylation; and when two cysteines are involved, disulfide formation. Glutathione-cysteine adducts may be removed from proteins by glutaredoxin, whereas disulfides may be reduced by thioredoxin. Glutaredoxin is homologous to the disulfide-reducing thioredoxin and shares similar binding modes of the protein substrate. The evolution of these systems is not well characterized. When a single Cys is present in a protein, conjugation of the redox buffer glutathione may induce conformational changes, resulting in a simple redox switch that effects a signaling cascade. If a second cysteine is introduced into the sequence, the potential for disulfide formation exists. In favorable protein contexts, a bistable redox switch may be formed. Because of glutaredoxin's similarities to thioredoxin, the mutated protein may be immediately exapted into the thioredoxin-dependent redox cycle upon addition of the second cysteine. Here we searched for examples of protein substrates where the number of redox-active cysteine residues has changed throughout evolution. We focused on cross-strand disulfides (CSDs), the most common type of forbidden disulfide. We searched for proteins where the CSD is present, absent and also found as a single cysteine in protein orthologs. Three different proteins were selected for detailed study-CD4, ERO1, and AKT. We created phylogenetic trees, examining when the CSD residues were mutated during protein evolution. We posit that the primordial cysteine is likely to be the cysteine of the CSD which undergoes nucleophilic attack by thioredoxin. Thus, a redox-active disulfide may be introduced into a protein structure by stepwise mutation of two residues in the native sequence to Cys. By extension, evolutionary acquisition of structural disulfides in proteins can potentially occur via transition through a redox-active disulfide state.

Dataset Information

Vitamin D status is independently associated with plasma glutathione and cysteine thiol/disulphide redox status in adults.

Publications

Vitamin D status is independently associated with plasma glutathione and cysteine thiol/disulphide redox status in adults.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets