| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
* To whom correspondence should be addressed. E-mail: ptappia{at}sbrc.ca.
The Ca2+-dependent phospholipase C (PLC) converts phosphatidylinositol 4,5-biphosphate to diacylglycerol (DAG) and iositol 1,4,5- trisphosphate (IP3). Since these products modulate Ca2+- movements in the myocardium, PLC may also contribute to a self-perpetuating cycle that exacerbates cardiomyocyte Ca2+-overload and subsequent cardiac dysfunction in ischemia-reperfusion (I-R). Although we have earlier reported that I-R induced changes in PLC isozymes might contribute to cardiac dysfunction, the present study was undertaken to examine the beneficial effects of the PLC inhibitor, U73122 as well as determining the role of Ca2+ on the I-R induced changes in PLC isozymes. Isolated rat hearts were subjected to global ischemia 30 min followed by 5 or 30 min of reperfusion. Pretreatment of hearts with U73122 (0.5 µM) significantly inhibited DAG and IP3 production in I-R and was associated with enhanced recovery of cardiac function as indicated by measurement of LVEDP, LVDP, +dP/dtmax and -dP/dtmax. Verapamil (0.1 µM), partially prevented the increase in sarcolemmal (SL) PLC 
1 activity in ischemia and the decrease in its activity during the reperfusion phase as well as elicited a partial protection of the depression in SL PLC 
1 and 
1 activities during the ischemic phase and attenuated the increase during the reperfusion period. Although these changes were associated with an improved myocardial recovery following I-R, verapamil was less effective than U73122. Perfusion with high Ca2+ resulted in the activation of the PLC isozymes studied and was associated with a markedly increased LVEDP and reduced LVDP, +dP/dtmax and -dP/dtmax. These results suggest that inhibition of PLC improves myocardial recovery following I-R.
This article has been cited by other articles:
|
|
 |
|
  T. Peng, E Shen, J. Fan, Y. Zhang, J. M. O. Arnold, and Q. Feng Disruption of phospholipase C{gamma}1 signalling attenuates cardiac tumor necrosis factor-{alpha} expression and improves myocardial function during endotoxemia Cardiovasc Res, April 1, 2008; 78(1): 90 - 97. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. B. Nicoud, C. D. Knox, C. M. Jones, C. D. Anderson, J. M. Pierce, A. E. Belous, T. M. Earl, and R. S. Chari 2-APB protects against liver ischemia-reperfusion injury by reducing cellular and mitochondrial calcium uptake Am J Physiol Gastrointest Liver Physiol, September 1, 2007; 293(3): G623 - G630. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Mangat, T. Singal, N. S. Dhalla, and P. S. Tappia Inhibition of phospholipase C-{gamma}1 augments the decrease in cardiomyocyte viability by H2O2 Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H854 - H860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Beisvag, P. K. Lehre, H. Midelfart, H. Aass, O. Geiran, A. K. Sandvik, A. Laegreid, J. Komorowski, and O. Ellingsen Aetiology-specific patterns in end-stage heart failure patients identified by functional annotation and classification of microarray data Eur J Heart Fail, June 1, 2006; 8(4): 381 - 389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. S. Tappia, M. S. Nijjar, A. Mahay, N. Aroutiounova, and N. S. Dhalla Phospholipid profile of developing heart of rats exposed to low-protein diet in pregnancy Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2005; 289(5): R1400 - R1406. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
