Glutathione and thioredoxin redox during differentiation in human colon epithelial (Caco-2) cells

Nkabyo, Yvonne S.; Ziegler, Thomas R.; Gu, Li H.; Watson, Walter H.; Jones, Dean P.

doi:10.1152/ajpgi.00183.2002

Cited by 200 publications

(149 citation statements)

References 33 publications

Supporting

Mentioning

131

Contrasting

Order By: Relevance

“…The finding that the steady-state redox potential of the GSH/ GSSG couple becomes progressively oxidized throughout the life cycle of cells (91,92,135) suggests that these three types Fig. 2.…”

Section: The Redox Hypothesismentioning

confidence: 99%

Radical-free biology of oxidative stress

Jones¹

2008

American Journal of Physiology-Cell Physiology

Self Cite

1,020

839

View full text Add to dashboard Cite

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...

show abstract

Section: The Redox Hypothesismentioning

confidence: 99%

Radical-free biology of oxidative stress

Jones¹

2008

American Journal of Physiology-Cell Physiology

Self Cite

1,020

839

View full text Add to dashboard Cite

show abstract

“…Not only is cellular GSH involved in proliferation, changes in the cellular GSH/Glutathione disulfide (GSSG) redox state (oxidative stress) have been implicated in cell cycle responses such as differentiation and apoptosis [61] . The redox status of the cells can be calculated by the Nernst equation for the couple GSSG/2GSH.…”

Section: Oxidative Stress and Hccmentioning

confidence: 99%

“…An imbalance in the redox homeostasis results in an increased flux of reactive oxygen species [63] . Under such pro-oxidant conditions, highly reactive radicals can damage DNA, RNA, proteins and lipid components, and this may lead to mutations or apoptosis [61,64] .…”

Section: Oxidative Stress and Hccmentioning

confidence: 99%

Tumor initiation and progression in hepatocellular carcinoma: risk factors, classification, and therapeutic targets

Severi¹,

Malenstein²,

Verslype³

et al. 2010

Acta Pharmacol Sin

157

125

View full text Add to dashboard Cite

“…While the Trx system and glutathione contribute significantly to the maintenance of cellular thiol redox balance, these systems are not in redox equilibrium with each other (Nkabyo et al, 2002;Hansen et al, 2006a). A major role of the thioredoxins is to maintain intracellular proteins in their reduced state (Arner and Holmgren, 2000), and the redox status of the thioredoxin (Trx) system in some cells may be more critical to cell survival than is glutathione.…”

Section: Introductionmentioning

confidence: 99%

Hexavalent chromium causes the oxidation of thioredoxin in human bronchial epithelial cells

2008

View full text Add to dashboard Cite

Hexavalent chromium [Cr(VI)] species such as chromates are cytotoxic. Inhalational exposure is a primary concern in many Cr-related industries and their immediate environments, and bronchial epithelial cells are directly exposed to inhaled Cr(VI). Chromates are readily taken up by cells and are reduced to reactive Cr species which may also result in the generation of reactive oxygen species (ROS). The thioredoxin (Trx) system has a key role in the maintenance of cellular thiol redox balance and is essential for cell survival. Cells normally maintain the cytosolic (Trx1) and mitochondrial (Trx2) thioredoxins largely in the reduced state. Redox western blots were used to assess the redox status of the thioredoxins in normal human bronchial epithelial cells (BEAS-2B) incubated with soluble Na 2 CrO 4 or insoluble ZnCrO 4 for different periods of time. Both chromates caused a doseand time-dependent oxidation of Trx2 and Trx1. Trx2 was more susceptible in that it could all be converted to the oxidized form, whereas a small amount of reduced Trx1 remained even after prolonged treatment with higher Cr concentrations. Only one of the dithiols, presumably the active site, of Trx1 was oxidized by Cr(VI). Cr(VI) did not cause significant GSH depletion or oxidation indicating that Trx oxidation does not result from a general oxidation of cellular thiols. With purified Trx and thioredoxin reductase (TrxR) in vitro, Cr(VI) also resulted in Trx oxidation. It was determined that purified TrxR has pronounced Cr(VI) reducing activity, so competition for electron flow from TrxR might impair its ability to reduce Trx. The in vitro data also suggested some direct redox interaction between Cr(VI) and Trx. The ability of Cr(VI) to cause Trx oxidation in cells could contribute to its cytotoxic effects, and could have important implications for cell survival, redoxsensitive cell signaling, and the cells' tolerance of other oxidant insults.

show abstract

Glutathione and thioredoxin redox during differentiation in human colon epithelial (Caco-2) cells

Cited by 200 publications

References 33 publications

Radical-free biology of oxidative stress

Radical-free biology of oxidative stress

Tumor initiation and progression in hepatocellular carcinoma: risk factors, classification, and therapeutic targets

Hexavalent chromium causes the oxidation of thioredoxin in human bronchial epithelial cells

Contact Info

Product

Resources

About