Diurnal variation in glutathione and cysteine redox states in human plasma

Blanco, Roberto; Ziegler, Thomas R.; Carlson, Bryce A.; Cheng, Po‐Yung; Park, Youngja; Cotsonis, George; Accardi, Carolyn Jonas; Jones, Dean P.

doi:10.1093/ajcn/86.4.1016

Cited by 167 publications

(155 citation statements)

References 33 publications

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“…These proteins may contribute to Cd-induced toxicity by concerning with GSH complexly, therefore, we protein levels and consider the contribution to the diurnal variation of Cd toxicity. There are many reports indicating the diurnal variation of GSH levels in plasma in addition to liver (Jaeschke and Wendel, 1985;Blanco et al, 2007;Xu et al, 2012). We estimated the hepatic levels of GSH in this report, therefore, we need further information about the GSH levels in plasma.…”

Section: Discussionmentioning

confidence: 97%

Mechanisms of cadmium-induced chronotoxicity in mice

et al. 2013

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-Biological defense factors show diurnal variations in their expression levels or activities. These variations can induce the different sensitivity to external toxicants of a day. We reported earlier that mice showed clear diurnal variation of cadmium (Cd)-induced toxicity, i.e., chronotoxicity. In this report, we investigated additional new evidences for the cadmium (Cd)-induced chronotoxicity, and considered the mechanisms contributed to this chronotoxicity. Male C57BL/6J mice were injected with CdCl 2 (6.4 mg/kg, one shot) intraperitoneally at 6 different time points of a day (zeitgeber time (ZT); ZT2, ZT6, ZT10, ZT14, ZT18 or ZT22) followed by monitoring the mortality until 14 days after the injection. We observed extreme difference in survival numbers: surprisingly, all mice died at ZT2 injection while all mice survived at ZT18 injection. Moreover, in non-lethal dose of Cd (4.5 mg/kg), the values of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) used as indexes of hepatotoxicity markedly increased at ZT6 injection while mostly unchanged at ZT18 injection. To consider the mechanisms of this extreme diurnal variation, we examined biochemical studies and concluded that the diurnal variation was not caused by the differences in hepatic Cd level, basal hepatic metallothionein (MT) level, and induction level or induction speed of hepatic MT. We suggested that one of the candidate determination factors was glutathione. We believe that the "chronotoxicology" for metal toxicity may be classic, yet new viewpoint

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Section: Discussionmentioning

confidence: 97%

Mechanisms of cadmium-induced chronotoxicity in mice

et al. 2013

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“…However, the extent to which NAC affects tissue GSH in humans is difficult to assess. Recent data showing that GSH/GSSG and Cys/CySS redox states undergo a diurnal variation linked to dietary intake of sulfur amino acids (16) suggest careful timing and dosing may be needed because NAC absorption and clearance are rapid. Furthermore, homeostatic regulation of Cys and GSH declines with age, and this occurs at a younger age in men than in women (16).…”

Section: Oxidative Stress As a Disruption Of Redox Signaling And Controlmentioning

confidence: 99%

“…Recent data showing that GSH/GSSG and Cys/CySS redox states undergo a diurnal variation linked to dietary intake of sulfur amino acids (16) suggest careful timing and dosing may be needed because NAC absorption and clearance are rapid. Furthermore, homeostatic regulation of Cys and GSH declines with age, and this occurs at a younger age in men than in women (16). Thus dosing regimens may be critical in development of antioxidant strategies designed to protect or correct disruption of thiol redox systems by nonradical oxidants.…”

Section: Oxidative Stress As a Disruption Of Redox Signaling And Controlmentioning

confidence: 99%

Radical-free biology of oxidative stress

Jones¹

2008

American Journal of Physiology-Cell Physiology

1,034

839

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Free radical-induced macromolecular damage has been studied extensively as a mechanism of oxidative stress, but large-scale intervention trials with free radical scavenging antioxidant supplements show little benefit in humans. The present review summarizes data supporting a complementary hypothesis for oxidative stress in disease that can occur without free radicals. This hypothesis, which is termed the "redox hypothesis," is that oxidative stress occurs as a consequence of disruption of thiol redox circuits, which normally function in cell signaling and physiological regulation. The redox states of thiol systems are sensitive to twoelectron oxidants and controlled by the thioredoxins (Trx), glutathione (GSH), and cysteine (Cys). Trx and GSH systems are maintained under stable, but nonequilibrium conditions, due to a continuous oxidation of cell thiols at a rate of about 0.5% of the total thiol pool per minute. Redox-sensitive thiols are critical for signal transduction (e.g., H-Ras, PTP-1B), transcription factor binding to DNA (e.g., Nrf-2, nuclear factor-B), receptor activation (e.g., ␣IIb␤3 integrin in platelet activation), and other processes. Nonradical oxidants, including peroxides, aldehydes, quinones, and epoxides, are generated enzymatically from both endogenous and exogenous precursors and do not require free radicals as intermediates to oxidize or modify these thiols. Because of the nonequilibrium conditions in the thiol pathways, aberrant generation of nonradical oxidants at rates comparable to normal oxidation may be sufficient to disrupt function. Considerable opportunity exists to elucidate specific thiol control pathways and develop interventional strategies to restore normal redox control and protect against oxidative stress in aging and age-related disease.thioredoxin; glutathione; cysteine; hydrogen peroxide; redox signaling; protein thiol ONE OF THE GREAT REDOX BIOLOGISTS of the past century, Howard S. Mason, professed that to advance science, a scientist must interpret observations at the limit of their meaning. The present review of the redox biology of thiol systems addresses the possibility that disruption of the function and homeostasis of thiol systems is the most central feature of oxidative stress that contributes to mechanisms of aging and age-related disease. I have termed this the "redox hypothesis" to facilitate distinction from free radical hypotheses.Many proteins contain redox-sensitive thiols, and reactions of thiol systems occur largely by nonradical two-electron transfers. Accumulating data show that central thiol-disulfide couples are maintained under nonequilibrium conditions in biological systems. This presents a condition wherein changes in abundance and distribution of redox catalysts and changes in rates of generation of relevant oxidants (e.g., peroxides) and precursors for NADPH supply can account for pathological effects of oxidative stress through altered functions of enzymes, receptors, transporters, transcription factors, and structural elements, without free ra...

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“…Previous studies have shown characteristic changes in plasma thiol levels and steady-state redox potential with age, becoming highly significant between young (<30) and older (>60) adults, irrespective of other demographic factors [1,[19][20][21][22]. To evaluate clinical utility of the FTMS method, 5 young (mean age = 25.7 ± 3.3 y) and 5 older (mean age = 67.8 ± 6.3 y) adults were recruited to determine the ability of the LC-FTMS method to detect and quantify plasma thiol levels and steady-state redox potential changes with age.…”

Section: Evaluation Of Plasma Thiol/disulfide Oxidative Stress With Agementioning

confidence: 99%

A rapid LC-FTMS method for the analysis of cysteine, cystine and cysteine/cystine steady-state redox potential in human plasma

Johnson

Strobel

Reed

et al. 2008

Clinica Chimica Acta

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Background-The steady-state redox potential of the cysteine/cystine couple in human plasma provides a measure of oxidative stress, yet available assays are limited by either specificity or speed of assay.Method-The present study evaluated the use of LC-FTMS for identification based on accurate mass combined with quantification by stable isotopic dilution to rapidly determine cysteine and cystine concentration and cysteine/cystine steady-state redox potential in human plasma.Results-A simple extraction procedure followed by a rapid LC separation eluted cysteine in 4 min and cystine in 1.5 min with simultaneous measurement of glutathione (GSH) and glutathione disulfide (GSSG). A study of five young (mean age = 25.7) subjects and 5 older (mean age = 67.8 y) subjects showed an increased oxidation with age.Conclusions-Analysis by LC-FTMS is suitable for high-throughput analysis of plasma cysteine, cystine and cysteine/cystine steady-state redox potential as clinical measures of oxidative stress.

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Diurnal variation in glutathione and cysteine redox states in human plasma

Abstract: Cys/CySS and GSH/GSSG redox states in human plasma undergo diurnal variation with an increased magnitude of variation in Cys/CySS redox state in older persons. This variation could alter sensitivity to oxidative stress over a course of hours.

Cited by 167 publications

References 33 publications

Mechanisms of cadmium-induced chronotoxicity in mice

Mechanisms of cadmium-induced chronotoxicity in mice

Radical-free biology of oxidative stress

A rapid LC-FTMS method for the analysis of cysteine, cystine and cysteine/cystine steady-state redox potential in human plasma

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