Optimal NFκB Mediated Transcriptional Responses in Jurkat T Cells Exposed to Oxidative Stress Are Dependent on Intracellular Glutathione and Costimulatory Signals

Ginn‐Pease, Margaret E.; Whisler, Ronald L.

doi:10.1006/bbrc.1996.1416

Cited by 93 publications

(38 citation statements)

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“…Development of oxidant/antioxidant imbalance in asthma leads to activation of redox-sensitive transcription factor NF-κB (Henderson et al, 2002). ROS have also been directly implicated as second messengers in the activation of NF-κB, based upon the ability of oxidants to activate NF-κB by the oxidation of its cysteine-SH group or by ubiquitination and proteolysis of IκB (Ginn-Pease and Whisler, 1996;Shang et al, 1997;Rahman and MacNee, 1998). Consistent with these observations, NF-κB levels in nuclear protein extracts from lung tissues were substantially increased in the OVA-induced model of allergic airway disease used for the present study.…”

Section: Discussionmentioning

confidence: 99%

A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-κB and hypoxia-inducible factor-1α

Lee

Kim²,

Park³

et al. 2007

Exp Mol Med

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Reactive oxygen species (ROS) play an important role in the pathogenesis of airway inflammation and hyperresponsiveness. Recent studies have demonstrated that antioxidants are able to reduce airway inflammation and hyperreactivity in animal models of allergic airway disease. A newly developed antioxidant, small molecular weight thiol compound, N-acetylcysteine amide (AD4) has been shown to increase cellular levels of glutathione and to attenuate oxidative stress related disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. However, the effects of AD4 on allergic airway disease such as asthma are unknown. We used ovalbumin (OVA)-inhaled mice to evaluate the role of AD4 in allergic airway disease. In this study with OVA-inhaled mice, the increased ROS generation, the increased levels of Th2 cytokines and VEGF, the increased vascular permeability, the increased mucus production, and the increased airway resistance in the lungs were significantly reduced by the administration of AD4. We also found that the administration of AD4 decreased the increases of the NF-κB and hypoxia-inducible factor-1α (HIF-1α ) levels in nuclear protein extracts of lung tissues after OVA inhalation. These results suggest that AD4 attenuates airway inflammation and hyperresponsiveness by regulating activation of NF-κB and HIF-1α as well as reducing ROS generation in allergic airway disease.

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Section: Discussionmentioning

confidence: 99%

A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-κB and hypoxia-inducible factor-1α

Lee

Kim²,

Park³

et al. 2007

Exp Mol Med

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“…However, if oxidant or other environmental stress alters this ratio, this shift in the GSH/GSSG redox buffer influences a variety of cellular signalling processes, such as activation of the transcription factors AP-1 and NF-kB. Oxidative stress including the presence of lipid peroxidation products [50] or depletion of GSH and subsequent increases in cytosolic GSSG in response to oxidative stress causes rapid ubiquitination and phosphorylation and thus subsequent degradation of the inhibitor of NF-kB (IkB), which is a critical step for NF-kB activation [51,52]. Under reducing conditions, such as an increase in intracellular GSH following treatment with N-acetyl-L-cysteine (NAC), the phosphorylation of serine groups on IkB-a following TNF-a treatment is inhibited, leading to the downregulation of NF-kB in endothelial cells ( fig.…”

Section: Activation Of Redox-sensitive Transcription Factorsmentioning

confidence: 99%

Oxidative stress and regulation of glutathione in lung inflammation

Rahman¹,

MacNee²

2000

Eur Respir J

811

555

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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.

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“…Oxidative stress has often been implicated in the functional loss accompanying aging, more specifically the involvement of thiols in T cell responsiveness to external stimuli [25][26][27][28][29]. However, there is little evidence for the effect of oxidative stress on proteasomal activities in primary human T lymphocytes.…”

Section: Introductionmentioning

confidence: 99%

Redox regulation of the proteasome in T lymphocytes during aging

Das

Ponnappan

2007

Free Radical Biology and Medicine

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Proteasome is a major cellular organelle responsible for the regulated turn-over of both normal and misfolded proteins. Recent reports from our laboratory have implicated lowered proteasomal chymotryptic activity to be responsible for decreased induction of the transcription factor NFκB in T lymphocytes during aging. In this study, we have further analyzed the basis for this decline in proteasomal function, by focusing on the role of oxidative stress. Upon exposure to the pro-oxidant BSO, both ATP-stimulatable 26S, as well as ATP-independent 20S proteasomal catalytic activity could be down-regulated in T cells from young donors, mimicking the decline observed in T cells from the elderly. Loss in these catalytic activities, following exposure to pro-oxidant stimulus also resulted in a decline in both activation-induced proliferation as well as degradation of the inhibitor IκBα, with concomitant increase in the accumulation of carbonylated proteins, mimicking responses seen in T cells from the elderly. Pretreatment with an antioxidant, NAC could override pro-oxidantmediated, but not age-associated decrease in both 20S proteasomal activities. These results suggest that the decrease in proteasomal activities observed during aging may be secondary to oxidative stress and underlie immune senescence.

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Optimal NFκB Mediated Transcriptional Responses in Jurkat T Cells Exposed to Oxidative Stress Are Dependent on Intracellular Glutathione and Costimulatory Signals

Cited by 93 publications

References 0 publications

A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-κB and hypoxia-inducible factor-1α

A novel thiol compound, N-acetylcysteine amide, attenuates allergic airway disease by regulating activation of NF-κB and hypoxia-inducible factor-1α

Oxidative stress and regulation of glutathione in lung inflammation

Redox regulation of the proteasome in T lymphocytes during aging

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