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    AMP-activated protein kinase response to contractions and treatment with the AMPK activator AICAR in young adult and old skeletal muscle

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    Author
    Thomson, D. M.; Brown, J. D.; Fillmore, N.; Ellworth, S. K.; Jacobs, D. L.; Winder, W. W.; Fick, C. A.; Gordon, Scott Edward
    Abstract
    One characteristic of aging skeletal muscle is a decline in mitochondrial function. Activation of AMP-activated protein kinase (AMPK)occurs in response to an increased AMP/ATP ratio,which is one potential result of mitochondrial dysfunction.We have previously observed higher AMPK activity in old (O; 30 months) vs young adult (YA; 8months) fast-twitch muscle in response to chronic overload. Here we tested the hypothesis that AMPK would also be hyperactivated in O vs YA fast-twitch extensor digitorum longus muscles from Fischer344 X Brown Norway (FBN) rats (n =8 per group) in response to high-frequency electrical stimulation of the sciatic nerve (HFES) or injection of AICAR, an activator of AMPK. Muscles were harvested immediately after HFES (10 sets of six 3-s contractions, 10 s rest between contractions, 1min rest between sets) or 1 h after AICAR injection (1mg (g body weight)-1 subcutaneously). The phosphorylations of AMPKalpha and acetyl-CoA carboxylase (ACC2; a downstream AMPK target) were both greatly increased (P less than or equal to 0.05) in response to HFES inOmuscles, but were either unresponsive (AMPKalpha) or much less responsive (ACC) in YA muscles. AMPKalpha2 activity was also greatly elevated in response to HFES in O muscles (but not YA muscles) despite a lower total AMPKalpha2 protein content in O vs YA muscles. In contrast, AMPKalpha2 activity was equally responsive to AICAR treatment in both age groups. Since mitochondrial content and/or efficiency could potentially underlie AMPK hyperactivation, we measured levels of mitochondrial proteins as well as citrate synthase (CS) activity. While CS activity was increased by 25% in O vs YA muscles, uncoupling protein-3 (UCP-3) protein level was upregulated with age by 353%. Thus,AMPK hyperactivation in response to contractile activity in aged fast-twitch muscle may be the result of compromised cellular energetics and not necessarily due to an inherent defect in responsiveness of the AMPK molecule per se. Originally published Journal of Physiology, Vol. 589, Pt. 9, May 2009
    URI
    http://hdl.handle.net/10342/3131
    Subject
     Skeletal muscle; Mitochondrial function; AMPK; High-frequency electrical stimulation 
    Date
    2009-05-01
    Citation:
    APA:
    Thomson, D. M., & Brown, J. D., & Fillmore, N., & Ellworth, S. K., & Jacobs, D. L., & Winder, W. W., & Fick, C. A., & Gordon, Scott Edward. (May 2009). AMP-activated protein kinase response to contractions and treatment with the AMPK activator AICAR in young adult and old skeletal muscle. Journal of Physiology, 587(9), 2077- 2086. Retrieved from http://hdl.handle.net/10342/3131

    Display/Hide MLA, Chicago and APA citation formats.

    MLA:
    Thomson, D. M., and Brown, J. D., and Fillmore, N., and Ellworth, S. K., and Jacobs, D. L., and Winder, W. W., and Fick, C. A., and Gordon, Scott Edward. "AMP-activated protein kinase response to contractions and treatment with the AMPK activator AICAR in young adult and old skeletal muscle". Journal of Physiology. 587:9. (2077-2086), May 2009. September 27, 2023. http://hdl.handle.net/10342/3131.
    Chicago:
    Thomson, D. M. and Brown, J. D. and Fillmore, N. and Ellworth, S. K. and Jacobs, D. L. and Winder, W. W. and Fick, C. A. and Gordon, Scott Edward, "AMP-activated protein kinase response to contractions and treatment with the AMPK activator AICAR in young adult and old skeletal muscle," Journal of Physiology 587, no. 9 (May 2009), http://hdl.handle.net/10342/3131 (accessed September 27, 2023).
    AMA:
    Thomson, D. M., Brown, J. D., Fillmore, N., Ellworth, S. K., Jacobs, D. L., Winder, W. W., Fick, C. A., Gordon, Scott Edward. AMP-activated protein kinase response to contractions and treatment with the AMPK activator AICAR in young adult and old skeletal muscle. Journal of Physiology. May 2009; 587(9): 2077-2086. http://hdl.handle.net/10342/3131. Accessed September 27, 2023.
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