| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Medicine, University of Wisconsin, Madison, WI, USA
2 Medicine, University of Wisconsin, Madison, WI, USA; Physiology, University of Wisconsin, Madison, WI, USA
* To whom correspondence should be addressed. E-mail: kws{at}medicine.wisc.edu.
While a diminished ability of tissues and organisms to tolerate stress is a clinically important hallmark of normal aging, little is known regarding its biochemical
basis. Our goal was to determine whether age-associated changes in AMP-activated protein kinase (AMPK), a key regulator of cellular metabolism during the stress response,
might contribute to the poor stress tolerance of aged cardiac and skeletal muscle. Basal AMPK activity and the degree of activation of AMPK by AMP and by in vivo hypoxemia (PaO2 of 39 mmHg), were measured in cardiac and skeletal muscle (gastrocnemius) from 5- and 24-month old C57Bl/6 mice. In the heart, neither basal AMPK activity nor its allosteric activation by AMP was affected by age. However, after 10 minutes of hypoxemia, the activity of 
2 AMPK, but not 1, was significantly higher in the hearts from old than from young mice (p<0.005), this difference being due to differences in phosphorylation of 2 AMPK. Significant activation of AMPK in the young hearts did not occur until 30 minutes of hypoxemia (p<0.0001), stress that was poorly tolerated by the old mice (mortality = 67%). In contrast, AMPK activity in gastrocnemius muscle was unaffected by age or hypoxemia. We conclude that the age-associated decline in hypoxic tolerance in cardiac and skeletal muscle is not caused by changes in basal AMPK activity or a blunted AMPK response to hypoxia. Activation of AMPK by in vivo hypoxia is slower and more modest than might be predicted from in vitro and ex vivo experiments.
This article has been cited by other articles:
|
|
 |
|
  J. D. Mulligan, A. A. Gonzalez, A. M. Stewart, H. V. Carey, and K. W. Saupe Upregulation of AMPK during cold exposure occurs via distinct mechanisms in brown and white adipose tissue of the mouse J. Physiol., April 15, 2007; 580(2): 677 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Al-Regaiey, M. M. Masternak, M. S. Bonkowski, J. A. Panici, J. J. Kopchick, and A. Bartke Effects of Caloric Restriction and Growth Hormone Resistance on Insulin-Related Intermediates in the Skeletal Muscle J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2007; 62(1): 18 - 26. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-H. Ning, S.-H. Chen, N. E. Buroker, C.-S. Xu, F.-R. Li, S.-P. Li, D.-S. Song, M. Ge, O. M. Hyyti, M. Zhang, et al. Short-cycle hypoxia in the intact heart: hypoxia-inducible factor 1{alpha} signaling and the relationship to injury threshold Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H333 - H341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. D. Wadley, R. S. Lee-Young, B. J. Canny, C. Wasuntarawat, Z. P. Chen, M. Hargreaves, B. E. Kemp, and G. K. McConell Effect of exercise intensity and hypoxia on skeletal muscle AMPK signaling and substrate metabolism in humans Am J Physiol Endocrinol Metab, April 1, 2006; 290(4): E694 - E702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Hancock, E. Janssen, and R. L. Terjung Contraction-mediated phosphorylation of AMPK is lower in skeletal muscle of adenylate kinase-deficient mice J Appl Physiol, February 1, 2006; 100(2): 406 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Thomson and S. E. Gordon Diminished overload-induced hypertrophy in aged fast-twitch skeletal muscle is associated with AMPK hyperphosphorylation J Appl Physiol, February 1, 2005; 98(2): 557 - 564. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
