Transient depletion of lung glutathione by diethylmaleate enhances oxygen toxicity

Deneke, Susan M.; Lynch, Berkley A.; Fanburg, B. L.

doi:10.1152/jappl.1985.58.2.571

Cited by 75 publications

(32 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although decreases in lung contents of GSH in animals exposed to hyperoxia have not been observed in most studies reported to date (21,22,28,38,39), fasting or limiting dietary protein intake can potentiate or accelerate the emergence of lung damage in animals exposed to hyperoxia (21, 39 -41). The increase in animal sensitivity to normobaric hyperoxia was paralleled by attenuation or prevention of the increases in lung GSH levels usually observed in animals fed normal diets after 24 to 48 h of normobaric hyperoxia.…”

Section: Discussionmentioning

confidence: 99%

“…Deneke and coworkers (21)(22)(23) showed that a low-protein diet exacerbated oxygen toxicity, but cysteine supplementation of the same low-protein diets returned susceptibility to hyperoxia to normal, whereas equimolar amounts of leucine were without effect. Deneke et al (21)(22)(23) concluded that exacerbation of hyperoxia lung injury was caused by insufficient supplies of cysteine or methionine, leading to an inability to increase GSH levels during hyperoxia. Stabler and coworkers (33) recently found that very premature baboons may have decreased cysteine availability or increased cysteine utilization, similar to the abnormalities previously shown in both preterm and term human infants in respiratory distress (34).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Effects of Fasting on Tissue Contents of Coenzyme A and Related Intermediates in Rats

JENNISKENS

2002

Pediatric Research

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Effects of Fasting on Tissue Contents of Coenzyme A and Related Intermediates in Rats

JENNISKENS

2002

Pediatric Research

View full text Add to dashboard Cite

“…Various forms of oxidant stress and NO also increase the activity of membrane cystine and glutamate transport leading to increased GSH synthesis in lung cells [90,122,127,128]. It has been clearly shown that the cystine uptake is the rate-limiting step for GSH synthesis in cultured lung cells, especially under conditions of oxidative stress [66,129].…”

Section: Role Of C-glutamyl Transpeptidase In the Regulation Of Glutamentioning

confidence: 99%

Oxidative stress and regulation of glutathione in lung inflammation

Rahman¹,

MacNee²

2000

Eur Respir J

802

555

View full text Add to dashboard Cite

Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance, a major cause of cell damage. The development of an oxidant/antioxidant imbalance in lung inflammation may activate redox‐sensitive transcription factors such as nuclear factor‐κB, and activator protein‐1 (AP‐1), which regulate the genes for pro‐inflammatory mediators and protective antioxidant genes. Glutathione (GSH), a ubiquitous tripeptide thiol, is a vital intra‐ and extracellular protective antioxidant against oxidative/nitrosative stresses, which plays a key role in the control of pro‐inflammatory processes in the lungs. Recent findings have suggested that GSH is important in immune modulation, remodelling of the extracellular matrix, apoptosis and mitochondrial respiration. The rate‐limiting enzyme in GSH synthesis is γ‐glutamylcysteine synthetase (γ‐GCS). The human γ‐GCS heavy and light subunits are regulated by AP‐1 and antioxidant response elements and are modulated by oxidants, phenolic antioxidants, growth factors, and inflammatory and anti‐inflammatory agents in lung cells. Alterations in alveolar and lung GSH metabolism are widely recognized as a central feature of many inflammatory lung diseases such as idiopathic pulmonary fibrosis, acute respiratory distress syndrome, cystic fibrosis and asthma. The imbalance and/or genetic variation in antioxidant γ‐GCS and pro‐inflammatory versus antioxidant genes in response to oxidative stress and inflammation in some individuals may render them more susceptible to lung inflammation. Knowledge of the mechanisms of GSH regulation and balance between the release and expression of pro‐ and anti‐inflammatory mediators could lead to the development of novel therapies based on the pharmacological manipulation of the production as well as gene transfer of this important antioxidant in lung inflammation and injury. This review describes the redox control and involvement of nuclear factor‐κB and activator protein‐1 in the regulation of cellular glutathione and γ‐glutamylcysteine synthetase under conditions of oxidative stress and inflammation, the role of glutathione in oxidant‐mediated susceptibility/tolerance, γ‐glutamylcysteine synthetase genetic susceptibility and the potential therapeutic role of glutathione and its precursors in protecting against lung oxidant stress, inflammation and injury.

show abstract

“…Increases in susceptibility to hyperoxic lung injury in experimental animals depleted of GSH or GSH-dependent antioxidant functions have been demonstrated in numerous studies (11)(12)(13)(14)(15). However, exposure of experimental animals to hyperoxia has not been found to lead to depletion of GSH (11)(12)(13)(14)(15)(16), as would be expected with a GSH threshold-dependent onset of lung injury (17).…”

mentioning

confidence: 97%

“…However, exposure of experimental animals to hyperoxia has not been found to lead to depletion of GSH (11)(12)(13)(14)(15)(16), as would be expected with a GSH threshold-dependent onset of lung injury (17). Although increases in lung GSSG contents concomitant with onset of hyperoxic lung injury have been observed (18,19), the absolute levels of GSSG attained have been limited (9,16,20,21), and significant S-thiolation of lung proteins has not been reported (22).…”

mentioning

confidence: 99%

CoASH and CoASSG Levels in Lungs of Hyperoxic Rats as Potential Biomarkers of Intramitochondrial Oxidant Stresses

O'Donovan

Rogers

Kelley³

et al. 2002

Pediatr Res

View full text Add to dashboard Cite

Coenzyme A (CoASH) is compartmentalized preferentially in the mitochondria, and CoASH and its mixed disulfide with glutathione (CoASSG) undergo thiol/disulfide exchange reactions with glutathione (GSH) and glutathione disulfide (GSSG) in vitro. We measured CoASH and CoASSG in freeze-clamped lung tissues from Fischer-344 and Sprague-Dawley rats maintained in room air or exposed to Ͼ95% O 2 for 48 h to test the hypothesis that oxidant stresses on lung thiol status would be observed in the CoASH/CoASSG redox couple, suggesting oxidant stress responses in the mitochondria. Lung tissue concentrations of CoASSG in the Fischer-344 rats declined from 0.89 Ϯ 0.15 to 0.51 Ϯ 0.13 nmol/g of lung after 48 h of hyperoxia. CoASH levels declined from 6.40 Ϯ 0.84 to 3.0 Ϯ 0.65 nmol/g of lung, and acetyl CoA levels also were lower in the lungs of animals exposed to hyperoxia. CoASH/CoASSG ratios were lower in animals exposed to hyperoxia, satisfying our previously defined criteria for an oxidant stress on this thiol/disulfide redox couple, but absolute CoASSG levels were not increased, as would be expected for oxidant stresses driven simply by increases in reactive oxygen species or other oxidants. Pulmonary edema was observed in the hyperoxic rats and accounted for some of the declines in CoASH concentrations, but CoASH contents per total lung also declined. Lung mitochondrial succinate dehydrogenase activities were not diminished in rats exposed to hyperoxia, indicating that the decreases in CoASH concentrations are not attributable to general destruction of lung mitochondria. Lung GSSG contents were greater in the hyperoxia animals, but GSH/GSSG ratios, which are dominated by extramitochondrial pools, did not decrease in these animals. The mechanisms responsible for, and the possible pathophysiologic consequences of, the decreases in lung CoASH concentrations are not evident from the data available at the present time, but the loss of more than half the tissue contents of CoASH is likely to generate additional metabolic effects that could have significant pathophysiologic consequences. Administration of supplemental oxygen remains an important therapy in the care of patients with pulmonary insufficiency, as is encountered in many prematurely born infants or in adults with acute respiratory distress. However, this supplemental oxygen can cause adverse effects, as has been observed in the lungs of experimental animals and humans exposed to elevated oxygen tensions (1-4). Cellular injury is manifested when the rates of generation of the reactive species are increased beyond the capacities of the antioxidant defense mechanisms, such as with exposure to hyperoxia (1,5,6), or when the functions of the antioxidant defense mechanisms are deficient, compromised, or developmentally unprepared, such as in prematurely born infants (3,7,8).In the course of exposure of experimental animals to Ͼ95% oxygen, a relatively prolonged period usually is observed in

show abstract

Transient depletion of lung glutathione by diethylmaleate enhances oxygen toxicity

Cited by 75 publications

References 0 publications

Effects of Fasting on Tissue Contents of Coenzyme A and Related Intermediates in Rats

Effects of Fasting on Tissue Contents of Coenzyme A and Related Intermediates in Rats

Oxidative stress and regulation of glutathione in lung inflammation

CoASH and CoASSG Levels in Lungs of Hyperoxic Rats as Potential Biomarkers of Intramitochondrial Oxidant Stresses

Contact Info

Product

Resources

About