AJP - Renal Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Renal Physiol (June 14, 2005). doi:10.1152/ajprenal.00081.2005
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
289/5/F1123    most recent
00081.2005v1
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 Tanaka, T.
Right arrow Articles by Nangaku, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tanaka, T.
Right arrow Articles by Nangaku, M.
Submitted on February 28, 2005
Accepted on June 10, 2005

Hypoxia-inducible factor (HIF) modulates tubular cell survival in cisplatin nephrotoxicity

Tetsuhiro Tanaka1, Ichiro Kojima1, Takamoto Ohse1, Reiko Inagi2, Toshio Miyata2, Julie R. Ingelfinger3, Toshiro Fujita1, and Masaomi Nangaku1*

1 Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, Tokyo, Japan
2 Institute of Medical Sciences, Tokai University, Kanagawa, Japan
3 Division of Pediatric Nephrology, Massachusetts General Hospital, Boston, MA, USA

* To whom correspondence should be addressed. E-mail: mnangaku-tky{at}umin.ac.jp.

Hypoxia-inducible factor (HIF) -1 is a transcription factor mediating cellular response to hypoxia. Although it is expressed in tubular cells of the ischemic kidney, its functional role is not fully clarified in the pathological context. Here we investigated a role of HIF in tubular cell apoptosis induced by cisplatin. HIF-1{alpha} was expressed in tubular cells in the outer medulla 3 days after cisplatin (6mg/kg) administration. By the in vivo administration of cobalt to activate HIF, the number of apoptotic renal tubular cells became much smaller in the outer medulla, as compared to the vehicle group. Then, the functional role of HIF-1 was examined in vitro using immortalized rat proximal tubular cells (IRPTC). In hypoxia, IRPTC that express dominant-negative (dn) HIF-1{alpha} showed impaired survival in cisplatin injury at variable doses (25-100µM, 24 h), which was not obvious in normoxia. The observed difference in cell viability in hypoxia was associated with the increased number of apoptosis in dnHIF-1{alpha} clones (Hoechst 33258 staining). Studies on intracellular signaling revealed that the degree of cytochrome c release, dissipation of mitochondrial membrane potentials, and caspase-9 activity were all more prominent in dnHIF-1{alpha} clones than in control IRPTC, pointing to the accelerated signaling of mitochondrial pathways. We propose that HIF-1 mediates cytoprotection against cisplatin injury in hypoxic renal tubular cells, by reducing the number of apoptosis through stabilization of mitochondrial membrane integrity and suppression of apoptosis signaling. A possibility was suggested that activation of HIF-1 could be a new promising therapeutic target for hypoxic renal diseases.




This article has been cited by other articles:


Home page
 Nephrol Dial TransplantHome page
S. Ohtomo, M. Nangaku, Y. Izuhara, S. Takizawa, C. v. Y. d. Strihou, and T. Miyata
Cobalt ameliorates renal injury in an obese, hypertensive type 2 diabetes rat model
Nephrol. Dial. Transplant., April 1, 2008; 23(4): 1166 - 1172.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
Y. A. Minamishima, J. Moslehi, N. Bardeesy, D. Cullen, R. T. Bronson, and W. G. Kaelin Jr
Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and congestive heart failure
Blood, March 15, 2008; 111(6): 3236 - 3244.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
A. Weidemann, W. M. Bernhardt, B. Klanke, C. Daniel, B. Buchholz, V. Campean, K. Amann, C. Warnecke, M. S. Wiesener, K.-U. Eckardt, et al.
HIF Activation Protects From Acute Kidney Injury
J. Am. Soc. Nephrol., March 1, 2008; 19(3): 486 - 494.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
J. B. Ray, S. Arab, Y. Deng, P. Liu, L. Penn, D. W. Courtman, and M. E. Ward
Oxygen regulation of arterial smooth muscle cell proliferation and survival
Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H839 - H852.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
B. Zhou, D. K. Ann, X. Li, K.-J. Kim, H. Lin, P. Minoo, E. D. Crandall, and Z. Borok
Hypertonic induction of aquaporin-5: novel role of hypoxia-inducible factor-1{alpha}
Am J Physiol Cell Physiol, April 1, 2007; 292(4): C1280 - C1290.
[Abstract] [Full Text] [PDF]

Home page
 J. Gerontol. A Biol. Sci. Med. Sci.Home page
T. Tanaka, H. Kato, I. Kojima, T. Ohse, D. Son, T. Tawakami, T. Yatagawa, R. Inagi, T. Fujita, and M. Nangaku
Hypoxia and expression of hypoxia-inducible factor in the aging kidney.
J. Gerontol. A Biol. Sci. Med. Sci., August 1, 2006; 61(8): 795 - 805.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
V. H. Haase
Hypoxia-inducible factors in the kidney
Am J Physiol Renal Physiol, August 1, 2006; 291(2): F271 - F281.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
J. Wang, M. P. Biju, M.-H. Wang, V. H. Haase, and Z. Dong
Cytoprotective Effects of Hypoxia against Cisplatin-Induced Tubular Cell Apoptosis: Involvement of Mitochondrial Inhibition and p53 Suppression
J. Am. Soc. Nephrol., July 1, 2006; 17(7): 1875 - 1885.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
M. Nangaku
Chronic Hypoxia and Tubulointerstitial Injury: A Final Common Pathway to End-Stage Renal Failure
J. Am. Soc. Nephrol., January 1, 2006; 17(1): 17 - 25.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.