Heme Oxygenase-1 Gene Expression by a Glutathione Depletor, Phorone, Mediated through AP-1 Activation in Rats

Oguro, Takiko; Hayashi, Masanori; Numazawa, Satoshi; Asakawa, Kiyoshi; Yoshida, Takemi

doi:10.1006/bbrc.1996.0583

Cited by 49 publications

(35 citation statements)

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“…reveals that in HEL30 keratinocytes there is no change in stk25 expression at 24 hr and a slight reduction at 4 hr (0.9-fold) after exposure to 2.5 µM arsenite. GSH attenuates the damaging effects of arsenite in numerous biological systems (26,29,30), and reduction in cellular GSH exacerbates cellular responses to redox-regulating agents (31,32) and arsenic (33,34). Figure 4 demonstrates that the addition of 100 µM BSO to culture medium shifts the LC 50 of arsenite 10-fold to approximately 1 µM in NHEK, suggesting that a reduction in GSH increases the potency of arsenite.…”

Section: Resultsmentioning

confidence: 99%

Sodium arsenite-induced stress-related gene expression in normal human epidermal, HaCaT, and HEL30 keratinocytes.

Trouba

Geisenhoffer

Germolec

2002

Environ Health Perspect

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Arsenic is a carcinogen that poses a significant health risk in humans. Based on evidence that arsenic has differential effects on human, rodent, normal, and transformed cells, these studies addressed the relative merits of using normal human epidermal keratinocytes (NHEK) and immortalized human (HaCaT) and mouse (HEL30) keratinocytes when examining stressinduced gene expression that may contribute to carcinogenesis. We hypothesize that redox-related gene expression is differentially modulated by arsenic in normal versus immortalized keratinocytes. To test the hypothesis, we exposed keratinocytes to sodium arsenite for 4 or 24 hr, at which time serine threonine kinase-25 (

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Section: Resultsmentioning

confidence: 99%

Sodium arsenite-induced stress-related gene expression in normal human epidermal, HaCaT, and HEL30 keratinocytes.

Trouba

Geisenhoffer

Germolec

2002

Environ Health Perspect

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“…Similarly, rats exposed to cigarette smoke have shown increased expression of genes encoding manganese SOD (MnSOD), metallothionein and glutathione peroxidase (GPx) in bronchial epithelial cells, suggesting the importance of the antioxidant gene adaptive response against the injurious effects of cigarette smoke [191]. Important protective antioxidant genes such as those encoding MnSOD, c-GCS-HS, haem oxygenase-1 (HO-1), GPx, thioredoxin reductase and metallothionein are induced by modulation of cellular GSH/GSSG levels in response to various oxidative stresses including hyperoxia and inflammatory mediators such as TNF-a and lipopolysaccharide in lung cells [85,86,141,192,193]. Thus oxidative/nitrosative stresses, including redox modulation, cause increased gene expression of proinflammatory genes via oxidant-mediated activation of transcription factors such as AP-1 and NF-kB and also activation of stress response protective genes such as c-GCS-HS, HO-1 and MnSOD in lungs.…”

Section: Antioxidant Protective Genesmentioning

confidence: 99%

“…The intracellular levels of GSH in fibroblasts modulate oxidant-induced expression of HO-1 [216]. This effect was due to the direct involvement of AP-1 (Jun/Jun) binding [192]. Similarly, metal-induced expression of the heat shock protein gene hsp72 is attenuated by glutathione, implying a protective role of GSH in acute inflammation [217].…”

Section: Against Inflammatory Events In Lungsmentioning

confidence: 99%

Oxidative stress and regulation of glutathione in lung inflammation

Rahman¹,

MacNee²

2000

Eur Respir J

812

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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“…NIH-PA Author Manuscript NIH-PA Author Manuscript that cause oxidative stress and/or in response to environmental stress [5][6][7][8]. For example, increased HO-1 expression has recently been found in the alveolar spaces in the resident macrophages of smokers [9].…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

HNE increases HO-1 through activation of the ERK pathway in pulmonary epithelial cells

Iles

Dickinson

Wigley

et al. 2005

Free Radical Biology and Medicine

101

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Heme oxygenase-1 (HO-1) is a key cytoprotective enzyme and an established marker of oxidative stress. Increased HO-1 expression has been found in the resident macrophages in the alveolar spaces of smokers. The lipid peroxidation product 4-hydroxynonenal (HNE) is also increased in the bronchial and alveolar epithelium in response to cigarette smoke. This suggests a link between a chronic environmental stress, HNE formation, and HO-1 induction. HNE is both an agent of oxidative stress in vivo and a potent cell signaling molecule. We hypothesize that HNE acts as an endogenously produced pulmonary signaling molecule that elicits an adaptive response culminating in the induction of HO-1. Here we demonstrate that HNE increases HO-1 mRNA, protein, and activity in pulmonary epithelial cells and identify ERK as a key pathway involved. Treatment with HNE increased ERK phosphorylation, c-Fos protein, JNK phosphorylation, c-Jun phosphorylation, and AP-1 binding. Whereas inhibiting the ERK pathway with the MEK inhibitor PD98059 significantly decreased HNEmediated ERK phosphorylation, c-Fos protein induction, AP-1 binding, and HO-1 protein induction, inhibition of the ERK pathway had no effect on HNE-induced HO-1 mRNA. This suggests that ERK is involved in the increase in HO-1 through regulation of translation rather than transcription. Keywords 4-Hydroxynonenal; Oxidative stress; HO-1; MAPK signaling; Free radicals Heme oxygenase-1 (HO-1) is an important cytoprotective enzyme and widely accepted marker of oxidative stress. HO-1 catalyzes the first and rate-limiting step in the catabolism of heme, which generates equimolar amounts of biliverdin, ferrous iron, and carbon monoxide [1][2][3]. Although heme is the major substrate of HO-1, a variety of non-heme-containing agents are also strong inducers of HO-1. HO-1 has been shown to respond to a number of proinflammatory cytokines, including TNF-α, . HO-1 is also induced by a variety of agents NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript that cause oxidative stress and/or in response to environmental stress [5][6][7][8]. For example, increased HO-1 expression has recently been found in the alveolar spaces in the resident macrophages of smokers [9]. Once induced, HO-1 provides protection against multiple types of tissue injury [10][11][12][13]; specific to the lung, overexpression of HO-1 in pulmonary epithelial cells has been shown to protect against oxygen toxicity [14]. In contrast, HO-1 deficiency in mice (HO-1 −/− ) increases susceptibility to inflammatory lung injury [15], as does HO-1 deficiency in humans [16]. Although the precise mechanisms by which HO-1 exerts its cytoprotective effects are not known, there is mounting evidence that carbon monoxide plays a key role in this process. For thorough reviews of the recent literature see [17,18].Another characteristic of oxidative stress is the formation of the lipid peroxidation product 4-hydroxy-2-nonenal (HNE). HNE has been shown to increase HO-1 in the cell [19,20], but the mechanism(s...

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Heme Oxygenase-1 Gene Expression by a Glutathione Depletor, Phorone, Mediated through AP-1 Activation in Rats

Cited by 49 publications

References 0 publications

Sodium arsenite-induced stress-related gene expression in normal human epidermal, HaCaT, and HEL30 keratinocytes.

Sodium arsenite-induced stress-related gene expression in normal human epidermal, HaCaT, and HEL30 keratinocytes.

Oxidative stress and regulation of glutathione in lung inflammation

HNE increases HO-1 through activation of the ERK pathway in pulmonary epithelial cells

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