| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Medicine, William S. Middleton VAMC/University of Wisconsin School of Medicine, Madison, United States
2 Medicine, San Francisco VAMC/University of California School of Medicine, San Francisco, San Francisco, California, United States
3 Medicine and Cardiovascular Research Institute, San Francisco VAMC/University of California School of Medicine, San Francisco, San Francisco, California, United States
* To whom correspondence should be addressed. E-mail: david.lovett{at}med.va.gov.
Matrix metalloproteinase-2 (MMP-2) is central to the to the cardiac injury response. Elevated MMP-2 after ischemia suggests new protein synthesis, but the molecular regulation of MMP-2 druing ischemia/reperfusion (I/R) injury has not been studied. Using the MMP-2 promoter linked to a 
-galactosidase reporter in transgenic mice, we investigated the transcriptional regulation and cellular sources of MMP-2 in isolated, perfused mouse hearts subjected to acute global I/R injury. I/R induced a rapid activation of MMP-2 promoter activity with the appearance of -galactosiase antigen in cardiomyocytes, fibroblasts and endothelial cells. Activation of intrinsic MMP-2 transcription and translation was confirmed by real time PCR and quantitative Western blot analyses. MMP-2 transcription and translation were inhibited by a hydroxyl radical scavenger. Nuclear extracts demonstrated inceased abundance of two AP-1 components, JunB and FosB, following I/R injury. Immunohistochemical staining localized JunB and FosB proteins to the nuclei of all three cardiac cell types following I/R injury, consistent with enhanced nuclear transport of these transcription factors. Chromatin immunoprecipitation (ChIP) of the AP-1 binding site in the intrinsic murine MMP-2 promoter yielded only JunB under control conditions, while ChIP following I/R injury recovered both JunB and FosB, consistent with a change in occupancy from JunB homodimers in controls to JunB/FosB heterodimers following I/R injury. Conclusions: enhanced MMP-2 trasncrition and translation following I/R injury is mediated by induction, via oxidant stress, of discrete AP-1 transcription factor components.
This article has been cited by other articles:
|
|
 |
|
  C. Hu, A. Dandapat, J. Chen, Y. Fujita, N. Inoue, Y. Kawase, K.-i. Jishage, H. Suzuki, T. Sawamura, and J. L. Mehta LOX-1 deletion alters signals of myocardial remodeling immediately after ischemia-reperfusion Cardiovasc Res, November 1, 2007; 76(2): 292 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. G. Spinale Myocardial Matrix Remodeling and the Matrix Metalloproteinases: Influence on Cardiac Form and Function Physiol Rev, October 1, 2007; 87(4): 1285 - 1342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Bergman, J. R. Teerlink, R. Mahimkar, L. Li, B.-Q. Zhu, A. Nguyen, S. Dahi, J. S. Karliner, and D. H. Lovett Cardiac matrix metalloproteinase-2 expression independently induces marked ventricular remodeling and systolic dysfunction Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1847 - H1860. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
