AJP - Renal Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Renal Physiol (March 15, 2005). doi:10.1152/ajprenal.00351.2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
289/2/F280    most recent
00351.2004v1
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 Covington, M. D.
Right arrow Articles by Parrish, A. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Covington, M. D.
Right arrow Articles by Parrish, A. R.
Submitted on September 16, 2004
Accepted on March 13, 2005

Ischemia-Induced Cleavage of Cadherins in NRK Cells: Evidence for a Role of Metalloproteinases

Marisa D. Covington1, Kayla J. Bayless2, Robert C. Burghardt3, George E. Davis2, and Alan R. Parrish1*

1 Department of Pharmacology and Toxicology, College of Medicine, Texas A&M University System Health Science Center, College Station, TX, USA
2 Department of Pathology and Laboratory Medicine, College of Medicine, Texas A&M University System Health Science Center, College Station, TX, USA
3 Department of Veterinary Integrated Biosciences, College of Veeterinary Medicine, Texas A&M University, College Station, TX, USA

* To whom correspondence should be addressed. E-mail: Parrish{at}medicine.tamhsc.edu.

Although ischemia has been shown to disrupt cell adhesion, the underlying molecular mechanism is unknown. In these studies, we adapted a model of ischemia/reperfusion to normal rat kidney (NRK) cells, examined disruption of the cadherin/catenin complex, and identified a role for matrix metalloproteinases (MMPs) in ischemia-induced cleavage of cadherins. In NRK cells, ischemia was induced by applying a thin layer of phosphate buffered saline (PBS) solution supplemented with calcium and magnesium and a layer of mineral oil, which restricts exposure to oxygen. NRK cells exhibited an extracellular 80 kDa and intracellular 40 kDa E-cadherin fragments after 4 hr of ischemia, and at 6 hr the expression of full length E-cadherin decreased. While no fragments of N-cadherin, {alpha}-catenin, and {gamma}-catenin were observed at any time point, the detectable levels of these proteins decreased during ischemia. Ischemia was detected by an increase in pimonidazole adducts, as well as an increase in glucose transporter-1 (GLUT-1) protein expression. Ischemia did not decrease cell number, but there was a decrease in ATP levels. In addition, there was no evidence of cleaved caspase 3 or 9 during 6 hr of ischemia. The MMP inhibitors, GM6001 and TAPI-O, inhibited cleavage and/or loss of E- and N-cadherin protein expression. TIMP-3 and to a lesser extent TIMP-2, but not TIMP-1, inhibits ischemic cleavage and/or loss of E- and N-cadherin. These results demonstrate that ischemia induces a selective metalloproteinase-dependent cleavage of E-cadherin and decrease in N-cadherin that is associated with a disruption of junctional contacts.




This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
A. Dwivedi, S. C. Slater, and S. J. George
MMP-9 and -12 cause N-cadherin shedding and thereby {beta}-catenin signalling and vascular smooth muscle cell proliferation
Cardiovasc Res, January 1, 2009; 81(1): 178 - 186.
[Abstract] [Full Text] [PDF]

Home page
 Reproductive SciencesHome page
L. K. Harris and J. D. Aplin
Vascular Remodeling and Extracellular Matrix Breakdown in the Uterine Spiral Arteries During Pregnancy
Reproductive Sciences, December 1, 2007; 14(8_suppl): 28 - 34.
[Abstract] [PDF]

Home page
 DiabetesHome page
D. Navaratna, P. G. McGuire, G. Menicucci, and A. Das
Proteolytic Degradation of VE-Cadherin Alters the Blood-Retinal Barrier in Diabetes
Diabetes, September 1, 2007; 56(9): 2380 - 2387.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
J. M. Catania, G. Chen, and A. R. Parrish
Role of matrix metalloproteinases in renal pathophysiologies
Am J Physiol Renal Physiol, March 1, 2007; 292(3): F905 - F911.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
P. M. Cummins, N. von Offenberg Sweeney, M. T. Killeen, Y. A. Birney, E. M. Redmond, and P. A. Cahill
Cyclic strain-mediated matrix metalloproteinase regulation within the vascular endothelium: a force to be reckoned with
Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H28 - H42.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
M. D. Covington, R. C. Burghardt, and A. R. Parrish
Ischemia-induced cleavage of cadherins in NRK cells requires MT1-MMP (MMP-14)
Am J Physiol Renal Physiol, January 1, 2006; 290(1): F43 - F51.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
G. E. Davis and D. R. Senger
Endothelial Extracellular Matrix: Biosynthesis, Remodeling, and Functions During Vascular Morphogenesis and Neovessel Stabilization
Circ. Res., November 25, 2005; 97(11): 1093 - 1107.
[Abstract] [Full Text] [PDF]


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