| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Laboratory of Muscle Biology and Sarcopenia, Divison of Exercise Physiology, West Virginia University School of Medicine, Morgantown, WV, USA
* To whom correspondence should be addressed. E-mail: salway{at}hsc.wvu.edu.
Hindlimb suspension induces extensive muscle atrophy in plantar flexor muscles that contain predominantly slow-twitch fibers (e.g., soleus). However, plantar flexor muscles containing a high percentage of fast twitch fibers (e.g., gastrocnemius) also atrophy. Although apoptosis has been demonstrated in soleus during hindlimb suspension, it is not known whether apoptosis is also involved in the loss of muscles dominated by mixed fibers. Moreover, the effect of aging on suspension-induced apoptosis in the predominately fast fibered muscle is unclear. Therefore, we examined the apoptotic responses in gastrocnemius muscles of young adult and aged Fischer344xBrown Norway rats after acute hindlimb suspension. Following 14 days of suspension, medial gastrocnemius muscle wet weight significantly decreased by 30% and 32%, and muscle wet weight normalized to the animal bodyweight decreased by 11% and 15% in young adult and aged animals, respectively. As determined by a cytosolic nucleosome ELISA, the extent of apoptotic DNA fragmentation increased by 119% and 61% in suspended gastrocnemius muscles from young and aged rats, respectively. RT-PCR analysis indicated that the transcriptional expression of Bax was elevated by 73% in young muscle following suspension. According to our immunoblot analyses, Bax and Bcl-2 protein levels were greater in the suspended muscle relative to the control sample in both young and aged animals. As demonstrated by the analyses of ELISA and immunoblots the level of cytosolic mitochondria-resided apoptotic factor cytochrome c was significantly increased in the mitochondria-free cytosol of suspended muscles from both young and aged rats. In contrast, the release/accumulation of AIF, a caspase-independent apoptogenic factor, was exclusively expressed in the suspended muscles from aged rats. Our data also show that aging favors the pro-apoptotic tendencies in skeletal muscle by altering the contents of Bax, Bcl-2, Apaf-1, AIF, caspases, XIAP, Smac/DIABLO, and cytochrome c. These results further clarify the response of apoptosis to hindlimb suspension-induced muscle disuse by demonstrating that apoptosis is activated not only in slow-twitch soleus muscle, but also in the mixed-fibered (predominately fast fibered) gastrocnemius muscle. Moreover, our data are consistent with the hypothesis that different apoptotic mechanisms may be responsible for the activation of apoptosis in young adult and aged gastrocnemius muscles during hindlimb suspension.
This article has been cited by other articles:
|
|
 |
|
  P. M. Siu, E. E. Pistilli, and S. E. Alway Age-dependent increase in oxidative stress in gastrocnemius muscle with unloading J Appl Physiol, December 1, 2008; 105(6): 1695 - 1705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Peterson, R. W. Bryner, A. Sindler, J. C. Frisbee, and S. E. Alway Mitochondrial apoptotic signaling is elevated in cardiac but not skeletal muscle in the obese Zucker rat and is reduced with aerobic exercise J Appl Physiol, December 1, 2008; 105(6): 1934 - 1943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Vazeille, A. Codran, A. Claustre, J. Averous, A. Listrat, D. Bechet, D. Taillandier, D. Dardevet, D. Attaix, and L. Combaret The ubiquitin-proteasome and the mitochondria-associated apoptotic pathways are sequentially downregulated during recovery after immobilization-induced muscle atrophy Am J Physiol Endocrinol Metab, November 1, 2008; 295(5): E1181 - E1190. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Gundersen and J. C. Bruusgaard Nuclear domains during muscle atrophy: nuclei lost or paradigm lost? J. Physiol., June 1, 2008; 586(11): 2675 - 2681. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. E. Pistilli, P. M. Siu, and S. E. Alway Interleukin-15 responses to aging and unloading-induced skeletal muscle atrophy Am J Physiol Cell Physiol, April 1, 2007; 292(4): C1298 - C1304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Adhihetty, M. F. N. O'Leary, B. Chabi, K. L. Wicks, and D. A. Hood Effect of denervation on mitochondrially mediated apoptosis in skeletal muscle J Appl Physiol, March 1, 2007; 102(3): 1143 - 1151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Adhihetty, V. Ljubicic, and D. A. Hood Effect of chronic contractile activity on SS and IMF mitochondrial apoptotic susceptibility in skeletal muscle Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E748 - E755. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. E. Dupont-Versteegden, B. A. Strotman, C. M. Gurley, D. Gaddy, M. Knox, J. D. Fluckey, and C. A. Peterson Nuclear translocation of EndoG at the initiation of disuse muscle atrophy and apoptosis is specific to myonuclei Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2006; 291(6): R1730 - R1740. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Rice, D. L. Preston, D. Neff, M. Norton, and E. R. Blough Age-Related Dystrophin-Glycoprotein Complex Structure and Function in the Rat Extensor Digitorum Longus and Soleus Muscle J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2006; 61(11): 1119 - 1129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Quadrilatero and J. W. E. Rush Increased DNA fragmentation and altered apoptotic protein levels in skeletal muscle of spontaneously hypertensive rats J Appl Physiol, October 1, 2006; 101(4): 1149 - 1161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. E. Dupont-Versteegden, J. D. Fluckey, M. Knox, D. Gaddy, and C. A. Peterson Effect of flywheel-based resistance exercise on processes contributing to muscle atrophy during unloading in adult rats J Appl Physiol, July 1, 2006; 101(1): 202 - 212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Csukly, A. Ascah, J. Matas, P. F. Gardiner, E. Fontaine, and Y. Burelle Muscle denervation promotes opening of the permeability transition pore and increases the expression of cyclophilin D J. Physiol., July 1, 2006; 574(1): 319 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Siu, E. E. Pistilli, Z. Murlasits, and S. E. Alway Hindlimb unloading increases muscle content of cytosolic but not nuclear Id2 and p53 proteins in young adult and aged rats J Appl Physiol, March 1, 2006; 100(3): 907 - 916. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
