AJP - Renal AJP: Advances in Physiology Education
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Renal Physiol (February 20, 2003). doi:10.1152/ajprenal.00017.2002
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
284/6/F1207    most recent
00017.2002v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
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 Google Scholar
Google Scholar
Right arrow Articles by Yang, Z.-Z.
Right arrow Articles by Zou, A.-P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yang, Z.-Z.
Right arrow Articles by Zou, A.-P.
Submitted on January 14, 2002
Accepted on February 11, 2003

REDOX REGULATION OF HIF-1{alpha} LEVELS AND HO-1 EXPRESSION IN RENAL MEDULLARY INTERSTITIAL CELLS

Zhi-Zhang Yang1, Andrew Y. Zhang1, Fu-Xian Yi1, Pin-Lan Li1, and Ai-Ping Zou1*

1 Departments of Physiology and Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA

* To whom correspondence should be addressed. E-mail: azou{at}mcw.edu.

The present study hypothesized that superoxide (O2.-) importantly contributes to the regulation of HIF-1{alpha} expression at posttranscriptional levels in renal medullary interstitial cells (RMICs) of rats. By Western blot analysis, it was found that incubation of RMICs with O2.- generators, xanthine/xanthine oxidase (X/XO) and menadione significantly inhibited hypoxia- or CoCl2-induced increase in HIF-1{alpha}levels and completely blocked the increase in HIF-1{alpha} levels induced by ubiquitin-proteasome inhibition with CBZ-LLL in the nuclear extracts from these cells. Under normoxic condition, a cell permeable O2.- dismutase (SOD) mimetic, 4-hydroxyl-tetramethylpiperidin-oxyl (TEMPOL) and PEG-SOD significantly increased HIF-1{alpha} levels in RMICs. Two mechanistically different inhibitors of NAD(P)H oxidase, diphenyleneiodonium (DPI) and apocynin were also found to increase HIF-1{alpha} levels in these renal cells. Moreover, introduction of an antisense oligodeoxynucleotide specific to NAD(P)H oxidase subunit, p22phox into RMICs markedly increased HIF-1{alpha}levels. In contrast, OH. scavenger tetramethylthiourea (TMTU) had no effect on the accumulation of HIF-1{alpha} in these renal cells. By Northern blot analysis, scavenging or dismutation of O2.- by TEMPOL and PEG-SOD was found to increase the mRNA levels of a HIF-1{alpha}-targeted gene, heme oxygenase-1. These results indicate that increased intracellular O2.- levels induces HIF-1{alpha} degradation independent of H2O2 and OH. radicals in RMICs. NAD(P)H oxidase activity may importantly contributes to this posttranscriptional regulation of HIF-1{alpha} in these cells under physiological condition.




This article has been cited by other articles:


Home page
 Pharmacol. Rev.Home page
C. S. Wilcox and A. Pearlman
Chemistry and Antihypertensive Effects of Tempol and Other Nitroxides
Pharmacol. Rev., December 1, 2008; 60(4): 418 - 469.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
A. A. Qutub and A. S. Popel
Reactive Oxygen Species Regulate Hypoxia-Inducible Factor 1{alpha} Differentially in Cancer and Ischemia
Mol. Cell. Biol., August 15, 2008; 28(16): 5106 - 5119.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
E. Daghini, X.-Y. Zhu, D. Versari, M. D. Bentley, C. Napoli, A. Lerman, and L. O. Lerman
Antioxidant vitamins induce angiogenesis in the normal pig kidney
Am J Physiol Renal Physiol, July 1, 2007; 293(1): F371 - F381.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
G. Zhang, F. Zhang, R. Muh, F. Yi, K. Chalupsky, H. Cai, and P.-L. Li
Autocrine/paracrine pattern of superoxide production through NAD(P)H oxidase in coronary arterial myocytes
Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H483 - H495.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
C. S. Wilcox
Oxidative stress and nitric oxide deficiency in the kidney: a critical link to hypertension?
Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2005; 289(4): R913 - R935.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. L. Ricker, Z. Chen, X. P. Yang, V. S. Pribluda, G. M. Swartz, and C. Van Waes
2-Methoxyestradiol Inhibits Hypoxia-Inducible Factor 1{alpha}, Tumor Growth, and Angiogenesis and Augments Paclitaxel Efficacy in Head and Neck Squamous Cell Carcinoma
Clin. Cancer Res., December 15, 2004; 10(24): 8665 - 8673.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
X.-Y. Zhu, A. R. Chade, M. Rodriguez-Porcel, M. D. Bentley, E. L. Ritman, A. Lerman, and L. O. Lerman
Cortical Microvascular Remodeling in the Stenotic Kidney: Role of Increased Oxidative Stress
Arterioscler Thromb Vasc Biol, October 1, 2004; 24(10): 1854 - 1859.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
M. Nikinmaa, S. Pursiheimo, and A. J. Soitamo
Redox state regulates HIF-1{alpha} and its DNA binding and phosphorylation in salmonid cells
J. Cell Sci., July 1, 2004; 117(15): 3201 - 3206.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1976 by the American Physiological Society.