| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Pharmacology and Toxicology, Brody School of Medicine at East Carolina University, Greenville, NC, USA
* To whom correspondence should be addressed. E-mail: abdelrahmana{at}mail.ecu.edu.
Although chronic and excessive alcohol consumption is associated with liver disease, the mechanism of alcoholic liver injury is still not clear. Whether reduced hepatic production of nitric oxide (NO), which is evident in models of liver injury, is associated with alcohol-induced liver injury has not been investigated. We measured NOS activity in the liver of pair-fed rats receiving liquid diet with or without alcohol (3%, v/v) for 12 weeks. Compared with control rats, hepatic NOS activity was significantly reduced in alcohol-treated rats along with the evidence of liver injury. Interestingly, there was no difference in the hepatic expression of eNOS between ethanol-fed and pair-fed rats. We then tested the hypothesis that an imbalance between the binding of eNOS with inhibitory and stimulatory proteins may underlie the reduced activity of eNOS because eNOS catalytic activity is regulated partly through dynamic interactions with the inhibitory protein, caveolin-1, and the stimulatory protein calmodulin. We found that hepatic caveolin-1 was markedly increased in alcohol-treated rats compared with control rats while calmodulin remained unaltered. The binding of caveolin-1 and calmodulin with the eNOS was increased and decreased, respectively, in alcohol-treated rats. Our results suggest that chronic alcohol intake attenuates hepatic eNOS activity by increasing the expression of the inhibitory protein caveolin-1, and enhancing its binding with eNOS.
This article has been cited by other articles:
|
|
 |
|
  J. Zhang and A. A. Abdel-Rahman Inhibition of Nischarin Expression Attenuates Rilmenidine-Evoked Hypotension and Phosphorylated Extracellular Signal-Regulated Kinase 1/2 Production in the Rostral Ventrolateral Medulla of Rats J. Pharmacol. Exp. Ther., January 1, 2008; 324(1): 72 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-L. Frossard, E. Schiffer, B. Cikirikcioglu, J. Bourquin, D. R. Morel, and C. M. Pastor Opposite regulation of endothelial NO synthase by HSP90 and caveolin in liver and lungs of rats with hepatopulmonary syndrome Am J Physiol Gastrointest Liver Physiol, October 1, 2007; 293(4): G864 - G870. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. El-Mas, J. Zhang, and A. A. Abdel-Rahman Upregulation of vascular inducible nitric oxide synthase mediates the hypotensive effect of ethanol in conscious female rats J Appl Physiol, March 1, 2006; 100(3): 1011 - 1018. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
