TGF-β<sub>1</sub>stimulates HO-1 via the p38 mitogen-activated protein kinase in A549 pulmonary epithelial cells

Ning, Wen; Song, Ruiping; Li, Chao Jun; Park, Edward; Mohsenin, Amir; Choi, Augustine M.K.; Choi, Mary E.

doi:10.1152/ajplung.00151.2002

Cited by 92 publications

(71 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The rapid induction of HO-1 mRNA also distinguishes our findings from those of other reports in the literature. Interestingly, one notable exception was the rapid response to TGF-β reported by Ning et al in pulmonary epithelial cells [34]. In this study, HO-1 mRNA increased at 1 h and protein at 3 h postincubation.…”

Section: Discussioncontrasting

confidence: 67%

“…Seminal studies support a role for these kinases as mediators of HO-1 induction in a broad range of tissues and cell types. Studies have shown that HO-1 is induced via the ERK pathway by LPS + IFN-γ [32], through p38 MAPK in murine macrophages in response to IL-1β, and in human lung epithelial cells by 34]. However, care must be taken not to generalize, as the signaling pathways that are activated are both agonist-and species-specific.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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...

show abstract

Section: Discussioncontrasting

confidence: 67%

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

View full text Add to dashboard Cite

show abstract

“…TGF β1 is known to induce HO-1 expression in pulmonary epithelial cells (Ning et al 2002), human renal proximal tubule cells (Hill-Kapturczak et al 2000), and also in WI-38 HDFs (Pascal et al 2007). HO-1 expression is transcriptionally activated by agents that generate reactive oxygen species (Soares and Bach 2009), and it has been already shown to be overexpressed in prematurely senescent WI-38 HDFs after exposure to t-BHP and ethanol (Pascal et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Copper ability to induce premature senescence in human fibroblasts

Matos

Gouveia

Almeida

2011

AGE

View full text Add to dashboard Cite

Human diploid fibroblasts (HDFs) exposed to subcytotoxic concentrations of oxidative or stressful agents, such as hydrogen peroxide, tertbutylhydroperoxide, or ethanol, undergo stressinduced premature senescence (SIPS). This condition is characterized by the appearance of replicative senescence biomarkers such as irreversible growth arrest, increase in senescence-associated β-galactosidase (SA β-gal) activity, altered cell morphology, and overexpression of several senescence-associated genes. Copper is an essential trace element known to accumulate with ageing and to be involved in the pathogenesis of some age-related disorders. Past studies using either yeast or human cellular models of ageing provided evidence in favor of the role of intracellular copper as a longevity modulator. In the present study, copper ability to cause the appearance of senescent features in HDFs was assessed. WI-38 fibroblasts exposed to a subcytotoxic concentration of copper sulfate presented inhibition of cell proliferation, cell enlargement, increased SA β-gal activity, and mRNA overexpression of several senescenceassociated genes such as p21, apolipoprotein J (ApoJ), fibronectin, transforming growth factor β-1 (TGF β1), insulin growth factor binding protein 3, and heme oxygenase 1. Western blotting results confirmed enhanced intracellular p21, ApoJ, and TGF β1 in copper-treated cells. Thus, similar to other SIPSinducing agents, HDF exposure to subcytotoxic concentration of copper results in premature senescence. Further studies will unravel molecular mechanisms and the biological meaning of copper-associated senescence and lead to a better understanding of copper-related disorder establishment and progression.

show abstract

“…Total protein of fibroblast was prepared and Western blotting was performed by using rabbit anti-Egr-1 antibody as described (18). Nuclear protein was prepared and Egr1 DNA-binding activity was measured by a BD Mercury TransFactor kit according to the manufacturer's instructions (BD Biosciences, Palo Alto, CA).…”

Section: Preparation and Treatment Of Cigarette Smoke Extract (Cse)mentioning

confidence: 99%

Comprehensive gene expression profiles reveal pathways related to the pathogenesis of chronic obstructive pulmonary disease

Ning

Kaminski

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

301

269

View full text Add to dashboard Cite

To better understand the molecular basis of chronic obstructive pulmonary disease (COPD), we used serial analysis of gene expression (SAGE) and microarray analysis to compare the gene expression patterns of lung tissues from COPD and control smokers. A total of 59,343 tags corresponding to 26,502 transcripts were sequenced in SAGE analyses. A total of 327 genes were differentially expressed (1.5-fold up-or down-regulated). Microarray analysis using the same RNA source detected 261 transcripts that were differentially expressed to a significant degree between GOLD-2 and GOLD-0 smokers. We confirmed the altered expression of a select number of genes by using real-time quantitative RT-PCR. These genes encode for transcription factors (EGR1 and FOS), growth factors or related proteins (CTGF, CYR61, CX3CL1, TGFB1, and PDGFRA), and extracellular matrix protein (COL1A1). Immunofluorescence studies on the same lung specimens localized the expression of Egr-1, CTGF, and Cyr61 to alveolar epithelial cells, airway epithelial cells, and stromal and inflammatory cells of GOLD-2 smokers. Cigarette smoke extract induced Egr-1 protein expression and increased Egr-1 DNA-binding activity in human lung fibroblast cells. Cytomix (tumor necrosis factor ␣, IL-1␤, and IFN-␥) treatment showed that the activity of matrix metalloproteinase-2 (MMP-2) was increased in lung fibroblasts from EGR1 control (؉/؉) mice but not detected in that of EGR1 null (؊/؊) mice, whereas MMP-9 was regulated by EGR1 in a reverse manner. Our study represents the first comprehensive analysis of gene expression on GOLD-2 versus GOLD-0 smokers and reveals previously unreported candidate genes that may serve as potential molecular targets in COPD.

show abstract

TGF-β₁stimulates HO-1 via the p38 mitogen-activated protein kinase in A549 pulmonary epithelial cells

Abstract: . TGF-␤1 stimulates HO-1 via the p38 mitogen-activated protein kinase in A549 pulmonary epithelial cells. Am

Cited by 92 publications

References 47 publications

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

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

Copper ability to induce premature senescence in human fibroblasts

Comprehensive gene expression profiles reveal pathways related to the pathogenesis of chronic obstructive pulmonary disease

Contact Info

Product

Resources

About

TGF-β1stimulates HO-1 via the p38 mitogen-activated protein kinase in A549 pulmonary epithelial cells

Abstract: . TGF-␤1 stimulates HO-1 via the p38 mitogen-activated protein kinase in A549 pulmonary epithelial cells. Am

Cited by 92 publications

References 47 publications

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

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

Copper ability to induce premature senescence in human fibroblasts

Comprehensive gene expression profiles reveal pathways related to the pathogenesis of chronic obstructive pulmonary disease

Contact Info

Product

Resources

About

TGF-β₁stimulates HO-1 via the p38 mitogen-activated protein kinase in A549 pulmonary epithelial cells