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Protein Kinase A-mediated CREB Phosphorylation is an Oxidant-induced Survival Pathway in Alveolar Type II Cells

Overview
Journal Apoptosis
Publisher Springer
Date 2008 Apr 9
PMID 18392938
Citations 22
Authors
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Abstract

Oxidant stress plays a role in the pathogenesis of pulmonary diseases, including fibrotic lung disease and cancer. We previously found that hydrogen peroxide (H2O2) initiates an increase in Ca2+/cAMP-response element binding protein (CREB) phosphorylation in C10 alveolar type II cells that requires activation of extracellular regulated kinases 1/2 (ERK1/2). Here, we investigated the role of crosstalk between protein kinase A (PKA) and epidermal growth factor receptor (EGFR) in oxidant-induced signaling to ERK1/2 and CREB in C10 cells. Application of H2O2 increased nuclear accumulation of PKA, and inhibition of PKA with H89 reduced oxidant-mediated phosphorylation of both CREB and ERK1/2. Single cell measurements of cAMP and redox status, using a FRET-based biosensor and a redox-sensitive GFP, respectively, indicated that H2O2 increases production of cAMP that correlates with redox state. Inhibition of EGFR activity decreased both H2O2-induced CREB phosphorylation and translocation of PKA to the nucleus, suggesting that crosstalk between PKA and EGFR underlies the oxidant-induced CREB response. Furthermore, knockdown of CREB expression using siRNA led to a decrease in bcl-2 and an increase in oxidant-induced apoptosis. Together these data reveal a novel role for crosstalk between PKA, ERK1/2 and CREB that mediates cell survival during oxidant stress.

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References
1.
Majidi M, Al-Wadei H, Takahashi T, Schuller H . Nongenomic beta estrogen receptors enhance beta1 adrenergic signaling induced by the nicotine-derived carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in human small airway epithelial cells. Cancer Res. 2007; 67(14):6863-71. DOI: 10.1158/0008-5472.CAN-07-0483. View

2.
Jimenez L, Zanella C, Fung H, Janssen Y, Vacek P, Charland C . Role of extracellular signal-regulated protein kinases in apoptosis by asbestos and H2O2. Am J Physiol. 1997; 273(5):L1029-35. DOI: 10.1152/ajplung.1997.273.5.L1029. View

3.
Mayr B, Montminy M . Transcriptional regulation by the phosphorylation-dependent factor CREB. Nat Rev Mol Cell Biol. 2001; 2(8):599-609. DOI: 10.1038/35085068. View

4.
Stevenson A, Cartin L, Wellman T, Dick M, Nelson M, Lounsbury K . Membrane depolarization mediates phosphorylation and nuclear translocation of CREB in vascular smooth muscle cells. Exp Cell Res. 2001; 263(1):118-30. DOI: 10.1006/excr.2000.5107. View

5.
Shukla A, Flanders T, Lounsbury K, Mossman B . The gamma-glutamylcysteine synthetase and glutathione regulate asbestos-induced expression of activator protein-1 family members and activity. Cancer Res. 2004; 64(21):7780-6. DOI: 10.1158/0008-5472.CAN-04-1365. View