| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
, ROS, and MPT
1 Dept of Biology, Portland State University, Portland, Oregon, United States
* To whom correspondence should be addressed. E-mail: garlid{at}pdx.edu.
Activation of protein kinase C epsilon (PKC
), opening of mitochondrial KATP channels (mitoKATP), and increase in mitochondrial reactive oxygen species (ROS) are key events in the signaling that underlies cardioprotection. However, the interactions among these and other components of the signaling cascades are not fully understood. Here, we investigate the relationships among PKC, mitoKATP, ROS, and MPT. We have shown that mitoKATP is opened by activation of a mitochondrial PKC that is closely associated with mitoKATP, which we designated PKC1. MitoKATP opening then causes an increase in ROS production by Complex I of the respiratory chain, and this activates PKC2, which inhibits the mitochondrial permeability transition (MPT). H2O2 and NO inhibit MPT opening, and both compounds do so independently of mitoKATP activity and via activation of PKC2. We show that mitoKATP can be opened by H2O2 and NO and that these effects are mediated by PKC1 and not by direct actions on mitoKATP. Superoxide has no effect on mitoKATP opening. MitoKATP opening induced by PKG, PMA or diazoxide was not sensitive to N-2-mercaptopropionyl glycine (MPG), showing that these modes of mitoKATP opening are not mediated by ROS. MitoKATP-generated ROS activates PKC1 and induces phosphorylation-dependent mitoKATP opening in vitro and in vivo. This mitoKATP-dependent mitoKATP opening constitutes a positive feedback loop that maintains the channel open after the stimulus is no longer present. This feedback pathway may be responsible for the memory effect of ischemic preconditioning.
This article has been cited by other articles:
|
|
 |
|
  C. Maack, E. R. Dabew, M. Hohl, H.-J. Schafers, and M. Bohm Endogenous Activation of Mitochondrial KATP Channels Protects Human Failing Myocardium From Hydroxyl Radical-Induced Stunning Circ. Res., October 9, 2009; 105(8): 811 - 817. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Srisakuldee, M. M. Jeyaraman, B. E. Nickel, S. Tanguy, Z.-S. Jiang, and E. Kardami Phosphorylation of connexin-43 at serine 262 promotes a cardiac injury-resistant state Cardiovasc Res, September 1, 2009; 83(4): 672 - 681. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Gao, C.-L. Long, R.-H. Wang, and H. Wang KATP activation prevents progression of cardiac hypertrophy to failure induced by pressure overload via protecting endothelial function Cardiovasc Res, August 1, 2009; 83(3): 444 - 456. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Boengler, R. Schulz, and G. Heusch Loss of cardioprotection with ageing Cardiovasc Res, July 15, 2009; 83(2): 247 - 261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Heusch, K. Boengler, and R. Schulz Cardioprotection: Nitric Oxide, Protein Kinases, and Mitochondria Circulation, November 4, 2008; 118(19): 1915 - 1919. [Full Text] [PDF]
|
|
|
|
|
|
P. Korge, P. Ping, and J. N. Weiss Reactive Oxygen Species Production in Energized Cardiac Mitochondria During Hypoxia/Reoxygenation: Modulation by Nitric Oxide Circ. Res., October 10, 2008; 103(8): 873 - 880. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
