| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 McGuire VA Medical Center, Richmond, Virginia, United States; Physiology, Virginia Commonwealth University, Richmond, Virginia, United States
2 McGuire VA Medical Center, Richmond, Virginia, United States; Physiology, Virginia Commonwealth University, Richmond, Virginia, United States; Medicine, Virginia Commonwealth University, Richmond, Virginia, United States
* To whom correspondence should be addressed. E-mail: schu{at}hsc.vcu.edu.
Oxidative stress often results in changes in gene expression through the regulation of transcription factors. In this study, we examine how Sp1 phosphorylation is regulated by H2O2 in the lung epithelial cell line HAE. Treatment of HAE cells with H2O2 increases phosphorylation of Sp1 and activates JNK. To establish a relationship between JNK and Sp1, we show that JNK activator anisomycin increases Sp1 phosphorylation, and JNK inhibitors as well as dominant negative JNK1 attenuate H2O2-induced Sp1 phosphorylation. Additionally, JNK1 directly phosphorylates Sp1 in vitro, reducing Sp1 binding to DNA. These results demonstrate a role of JNK in H2O2-induced Sp1 phosphorylation. Because H2O2 inhibits Ser/Thr protein phosphatase 1 (PP1), we examined the role of PP1 in the regulation of JNK. Similar to H2O2, inhibition of PP1 induces phosphorylation of Sp1 and activation of JNK in HAE cells. Inhibition of JNK activity using either inhibitors or dominant negative mutant JNK1 suppresses PP1 inhibition-induced Sp1 phosphorylation. Furthermore, PP1 directly inactivates JNK1 in vitro. These data suggest that H2O2 increases the phosphorylation level of Sp1; Sp1 is a target of the JNK pathway; PP1 regulates JNK activation; and the "PP1-JNK" pathway plays a role in H2O2-induced Sp1 phosphorylation in lung epithelial cells.
This article has been cited by other articles:
|
|
 |
|
  I. Kuwahara, E. P. Lillehoj, T. Koga, Y. Isohama, T. Miyata, and K. C. Kim The Signaling Pathway Involved in Neutrophil Elastase Stimulated MUC1 Transcription Am. J. Respir. Cell Mol. Biol., December 1, 2007; 37(6): 691 - 698. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Coffey, C. H. Serezani, S. M. Phare, N. Flamand, and M. Peters-Golden NADPH oxidase deficiency results in reduced alveolar macrophage 5-lipoxygenase expression and decreased leukotriene synthesis J. Leukoc. Biol., December 1, 2007; 82(6): 1585 - 1591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Fountain, A. Cheong, J. Li, N. Y. Dondas, F. Zeng, I. C. Wood, and D. J. Beech Kv1.5 potassium channel gene regulation by Sp1 transcription factor and oxidative stress Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2719 - H2725. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Xu, T. J. Ferro, and S. Chu Cigarette smoke condensate inhibits ENaC {alpha}-subunit expression in lung epithelial cells Eur. Respir. J., October 1, 2007; 30(4): 633 - 642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Norkina, A. Dolganiuc, T. Shapiro, K. Kodys, P. Mandrekar, and G. Szabo Acute alcohol activates STAT3, AP-1, and Sp-1 transcription factors via the family of Src kinases to promote IL-10 production in human monocytes J. Leukoc. Biol., September 1, 2007; 82(3): 752 - 762. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
