Extracellular Regulated Kinase/Mitogen Activated Protein Kinase Is Up-regulated in Pulmonary Emphysema and Mediates Matrix Metalloproteinase-1 Induction by Cigarette Smoke

Mercer, Becky A.; Kolesnikova, Natalia; Sonett, Joshua R.; DʼArmiento, Jeanine

doi:10.1074/jbc.m313842200

Cited by 158 publications

(193 citation statements)

References 40 publications

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“…Moreover, immunohistochemistry on emphysematous lung tissue has shown that MMP-1 is expressed in epithelial cells, especially type II pneumocytes. Increased MMP-1 expression in the epithelial cells of smokers may result from a prolonged activation of the ERK mitogen-activated protein kinase pathway (Mercer et al, 2004). These data suggest that inflammatory cells may not be exclusively responsible for lung tissue destruction, but that MMP-1 expression in epithelial cells can cause emphysema .…”

Section: Neoplastic Diseasesmentioning

confidence: 76%

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Sbardella

Fasciglione

Gioia

et al. 2012

Molecular Aspects of Medicine

208

212

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a b s t r a c tHuman matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn 2+ atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes.

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Section: Neoplastic Diseasesmentioning

confidence: 76%

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Sbardella

Fasciglione

Gioia

et al. 2012

Molecular Aspects of Medicine

208

212

View full text Add to dashboard Cite

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“…However, previous reports have also shown that MMP-1 is induced in NHBE cells exposed to cigarette (Imai et al, 2001;Maunders et al, 2007;Mercer et al, 2004). It is possible that proteins such as MMP-1 are expressed at levels that are sufficient to cause destruction to the lung by acting in their immediate surroundings but will be difficult to detect by conventional methods, such as Western blotting.…”

Section: Discussionmentioning

confidence: 93%

Effects Of 10 Cigarette Smoke Condensates On Primary Human Airway Epithelial Cells By Comparative Gene And Cytokine Expression Studies

Pickett¹,

Seagrave²,

Boggs³

et al. 2010

D23. Recent Advances on Smoking Health Effects

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Cigarettes vary in tobacco blend, filter ventilation, additives, and other physical and chemical properties, but little is known regarding potential differences in toxicity to a smoker's airway epithelia. We compared changes in gene expression and cytokine production in primary normal human bronchial epithelial cells following treatment for 18 h with cigarette smoke condensates (CSCs) prepared from five commercial and four research cigarettes, at doses of~4 mg/ml nicotine. Nine of the CSCs were produced under a standard International Organization for Standardization smoking machine regimen and one was produced by a more intense smoking machine regimen. Isolated messenger RNA (mRNA) was analyzed by microarray hybridization, and media was analyzed for secreted cytokines and chemokines. Twenty-one genes were differentially expressed by at least 9 of the 10 CSCs by more than twofold, including genes encoding detoxifying and antioxidant proteins. Cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) and NAD(P)H dehydrogenase, quinone 1 (NQO-1) were selected for validation with quantitative real-time PCR (qRT-PCR) and Western blot analyses. NQO-1 expression determined with microarrays, qRT-PCR, and Western blotting differed among the CSC types, with good correlation among the different assays. CYP1A1 mRNA levels varied substantially, but there was little correlation with the protein levels. For each CSC, the three most induced and three most repressed genes were identified. These genes may be useful as markers of exposure to that particular cigarette type. Furthermore, differences in interleukin-8 secretion were observed. These studies lay the foundation for future investigations to analyze differences in the responses of in vivo systems to tobacco products marketed with claims of reduced exposure or reduced harm.

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“…[33][34][35][36][37][38] We have suggested that EGR-1 can also stimulate HSP70 elevation in an ERK 1/2-dependent manner, which is thought to regulate cigarette smoke-induced inflammatory processes. 18 Here we provide the first evidence that EGR-1 could activate MAPK ERK 1/2 in a positive feedback manner through increasing Ras prenylation by promoting GGPPS transcription in lung epithelial cells during CSE challenge (Figure 6).…”

Section: Discussionmentioning

confidence: 99%

GGPPS, a New EGR-1 Target Gene, Reactivates ERK 1/2 Signaling through Increasing Ras Prenylation

Shen

Shao

Lai

et al. 2011

The American Journal of Pathology

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Cigarette smoke activates the extracellular signal-regulated kinase (ERK) 1/2 mitogen activated-protein kinase pathway, which, in turn, is responsible for early growth response gene-1 (EGR-1) activation. Here we provide evidence that EGR-1 activation can also reactivate ERK 1/2 mitogen activated-protein kinase through a positive feedback loop through its target gene (geranylgeranyl diphosphate synthase) GGPPS. For the first time, the GGPPS gene is identified as a target of EGR-1, as EGR-1 can directly bind to the predicted consensus-binding site in the GGPPS promoter and regulate its transcription. Long-term observations show that there are two ERK 1/2 phosphorylation peaks after cigarette smoke extract stimulation in human lung epithelial Beas-2B cells. The first peak (at 10 minutes) is responsible for EGR-1 accumulation, and the second (at 4 hours) is diminished after the disruption of EGR-1 transcriptional activity. EGR-1 overexpression enhances Ras prenylation and membrane association in a GGPPS-dependent manner, and it augments ERK 1/2 activation. Likewise, a great reduction of the second peak of ERK 1/2 phosphorylation is observed during long-term cigarette smoke extract stimulation in cells where GGPPS is disrupted. Thus, we have uncovered an intricate positive feedback loop in which ERK 1/2-activated EGR-1 promotes ERK 1/2 reactivation through promoting GGPPS transcription, which might affect cigarette smoke-related lung pathological processes.

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Extracellular Regulated Kinase/Mitogen Activated Protein Kinase Is Up-regulated in Pulmonary Emphysema and Mediates Matrix Metalloproteinase-1 Induction by Cigarette Smoke

Cited by 158 publications

References 40 publications

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Effects Of 10 Cigarette Smoke Condensates On Primary Human Airway Epithelial Cells By Comparative Gene And Cytokine Expression Studies

GGPPS, a New EGR-1 Target Gene, Reactivates ERK 1/2 Signaling through Increasing Ras Prenylation

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