Am J Physiol Cell Physiol Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol 284: C1090-C1099, 2003. First published December 4, 2002; doi:10.1152/ajpcell.00394.2002
0363-6143/03 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
284/4/C1090    most recent
00394.2002v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (11)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Guo, H.
Right arrow Articles by Kuo, P. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Guo, H.
Right arrow Articles by Kuo, P. C.
Vol. 284, Issue 4, C1090-C1099, April 2003

Serine/threonine phosphorylation regulates HNF-4alpha -dependent redox-mediated iNOS expression in hepatocytes

Hongtao Guo1, Junping Wei1, Yusuke Inoue2, Frank J. Gonzalez2, and Paul C. Kuo1

1 Duke University Medical Center, Durham, North Carolina 27710; and 2 National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20817

Nitric oxide (NO), endogenously synthesized by inducible NO synthase (iNOS), serves antioxidant and antiapoptotic functions in settings characterized by oxidative stress and proinflammatory cytokines such as sepsis and shock. However, the redox-sensitive mechanisms regulating hepatocyte expression of iNOS are largely unknown. In interleukin-1beta (IL-1beta )-stimulated hepatocytes exposed to superoxide, we demonstrate that hepatocyte nuclear factor-4alpha (HNF-4alpha ) acts as an activator of redox-associated hepatocyte iNOS expression at the level of protein, mRNA, and promoter activation. In the absence of HNF-4alpha , this redox-mediated enhancement is ablated. HNF-4alpha functional activity is associated with a unique serine/threonine kinase-mediated phosphorylation pattern. This suggests that a redox-sensitive kinase pathway targets HNF-4alpha to augment hepatocyte iNOS expression. Previous studies have not addressed a redox-dependent kinase signaling pathway that targets HNF-4alpha and enhances hepatocyte iNOS gene transcription. A unique pattern of phosphorylation determines HNF-4alpha activity as a trans-activator of IL-1beta -mediated hepatocyte iNOS expression in the presence of oxidative stress.

kinase; phosphorylation; nitric oxide; Cre-lox; transcription; inducible nitric oxide synthase; hepatocyte nuclear factor-4alpha


This article has been cited by other articles:


Home page
 J BiochemHome page
H. Guo, C. Gao, Z. Mi, J. Zhang, and P. C. Kuo
Characterization of the PC4 Binding Domain and its Interactions with HNF4{alpha}
J. Biochem., May 1, 2007; 141(5): 635 - 640.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
D. Sauvaget, V. Chauffeton, S. Dugue-Pujol, A.-D. Kalopissis, I. Guillet-Deniau, F. Foufelle, J. Chambaz, A. Leturque, P. Cardot, and A. Ribeiro
In Vitro Transcriptional Induction of the Human Apolipoprotein A-II Gene by Glucose
Diabetes, March 1, 2004; 53(3): 672 - 678.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
P.-Y. Cheng, M. Wang, and E. T. Morgan
Rapid Transcriptional Suppression of Rat Cytochrome P450 Genes by Endotoxin Treatment and Its Inhibition by Curcumin
J. Pharmacol. Exp. Ther., December 1, 2003; 307(3): 1205 - 1212.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online