Protein kinase A-mediated CREB phosphorylation is an oxidant-induced survival pathway in alveolar type II cells.
Protein kinase A-mediated CREB phosphorylation is an oxidant-induced survival pathway in alveolar type II cells.
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蛋白激酶A介导的CREB磷酸化是氧化剂诱导的II型细胞中的生存途径。
DOI：
10.1007/s10495-008-0203-z
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发表时间：
2008-05
期刊：
影响因子：
7.2
通讯作者：
Lounsbury, Karen M.
中科院分区：
文献类型：
--
作者：
Barlow, Christy A.;Kitiphongspattana, Kajorn;Siddiqui, Nazli;Roe, Michael W.;Mossman, Brooke T.;Lounsbury, Karen M.
氧化应激在肺部疾病的发病机制中起作用，包括纤维化肺病和癌症。我们以前发现，过氧化氢（H2 O2）启动增加Ca 2 +/cAMP反应元件结合蛋白（CREB）磷酸化C10肺泡II型细胞，需要激活细胞外调节激酶1/2（ERK 1/2）。在这里，我们研究了蛋白激酶A（PKA）和表皮生长因子受体（EGFR）之间的串扰在C10细胞中氧化诱导的ERK 1/2和CREB信号传导中的作用。H2 O2的应用增加了PKA的核积累，并且用H89抑制PKA减少了CREB和ERK 1/2的氧化剂介导的磷酸化。cAMP和氧化还原状态的单细胞测量，分别使用基于FRET的生物传感器和氧化还原敏感的GFP，表明H2 O2增加与氧化还原状态相关的cAMP的产生。EGFR活性的抑制降低了H2 O2诱导的CREB磷酸化和PKA易位到细胞核，这表明PKA和EGFR之间的串扰是氧化剂诱导的CREB反应的基础。此外，使用siRNA敲低CREB表达导致bcl-2减少和氧化剂诱导的细胞凋亡增加。总之，这些数据揭示了PKA，ERK 1/2和CREB之间的串扰介导的氧化应激过程中的细胞存活的新作用。
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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DOI：
10.1165/rcmb.2005-0153oc
发表时间：
2006-01-01
影响因子：
6.4
作者：
Barlow, C;Shukla, A;Lounsbury, KM
通讯作者：
Lounsbury, KM
影响因子：
4.1
作者：
CLARK, S;KONSTANTOPOULOS, N
通讯作者：
KONSTANTOPOULOS, N
影响因子：
5.3
作者：
Dumaz, N;Light, Y;Marais, R
通讯作者：
Marais, R
影响因子：
16.2
作者：
Impey, S;Obrietan, K;Storm, DR
通讯作者：
Storm, DR
影响因子：
11.2
作者：
Majidi, Mourad;Al-Wadei, Hussein A.;Schuller, Hildegard M.
通讯作者：
Schuller, Hildegard M.