Adaptive response of slow and fast skeletal muscle following mechanical hindlimb suspension in Wistar male rats

Document Type : Original Article

Authors

1 Department of Physical Education and Sport Sciences, Faculty of Literature and Human Sciences, Lorestan University, Khoramabad, Iran.

2 Department of Physical Education and Sports Sciences, Faculty of Literature and Human Sciences, Vali E Asr University of Rafsanjan, Rafsanjan, Iran.

3 Department of Anatomical Sciences, Faculty of Medicine, Lorestan University of Medical Sciences, Khoramabad, Iran.

Abstract

Mechanical hindlimb suspension of lower extremities leads to prompt atrophy in rats' skeletal muscles. The present research was designed to study cross-section area (CSA) and the expression level of the genes ATF4, P53, MST1, and atrogin-1 in slow and fast skeletal muscles following mechanical hindlimb suspension. 20 male Wistar rats were assigned randomly in to two groups: control (Con) and hind-limb suspension (HU) (10 rats per each group). In HU group, tail suspension was designed for 14 constitutive days; however, animals in the control group passed a normal life.  The findings indicated that hind-limb suspension could relatively diminish CSA, myonuclei number per fiber and the weight of both soleus and EDL muscles. However, these reductions were not significant for EDL muscle. Furthermore, the expression level of the MST1, atrogin-1, ATF4, and p53 in soleus muscles elevated significantly. Moreover, the expression level of all four genes increased significantly in EDL muscle. Comparison of genes expression level between two soleus and EDL muscles showed that expression of MST1, ATF4, and p53 genes were higher in soleus than EDL, but it was not the case for atrogin-1 as its expression level was more in EDL compared to soleus. Our study provides novel evidence that immobilization of hind-limbs can induce a more powerful atrophic response in slow muscles in comparison to fast ones.

What is already known on this subject?

Mechanical hindlimb suspension of lower extremities leads to prompt atrophy in rats' skeletal muscles.

 

What this study adds?

This study suggests that ATf4, P53, MST1, and atrogin-1 gene expression in soleus and EDL muscles under immobility due to the suspension of posterior organ increases by various levels.

Keywords

Main Subjects


Acharyya, S., Ladner, K. J., Nelsen, L. L., Damrauer, J., Reiser, P. J., Swoap, S., & Guttridge, D. C. (2004). Cancer cachexia is regulated by selective targeting of skeletal muscle gene products. J Clin Invest, 114(3), 370-378. doi: https://doi.org/10.1172/jci20174
Adams, G. R., Caiozzo, V. J., & Baldwin, K. M. (2003). Skeletal muscle unweighting: Spaceflight and ground-based models. J Appl Physiol (1985), 95(6), 2185-2201. doi: https://doi.org/10.1152/japplphysiol.00346.2003
Baldwin, K., Haddad, F., Pandorf, C., Roy, R., & Edgerton, R. (2013). Alterations in muscle mass and contractile phenotype in response to unloading models: Role of transcriptional/pretranslational mechanisms. Frontiers in Physiology, 4(284). doi: https://doi.org/10.3389/fphys.2013.00284
Berg, H. E., Larsson, L., & Tesch, P. A. (1997). Lower limb skeletal muscle function after 6 wk of bed rest. J Appl Physiol (1985), 82(1), 182-188. doi: https://doi.org/10.1152/jappl.1997.82.1.182
Bialek, P., Morris, C., Parkington, J., St Andre, M., Owens, J., Yaworsky, P., . . . Jelinsky, S. A. (2011). Distinct protein degradation profiles are induced by different disuse models of skeletal muscle atrophy. Physiol Genomics, 43(19), 1075-1086. doi: https://doi.org/10.1152/physiolgenomics.00247.2010
Bodine, S. C., & Baehr, L. M. (2014). Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx/atrogin-1. Am J Physiol Endocrinol Metab, 307(6), E469-484. doi: https://doi.org/10.1152/ajpendo.00204.2014
Bonaldo, P., & Sandri, M. (2013). Cellular and molecular mechanisms of muscle atrophy. Disease Models & Mechanisms, 6(1), 25-39. doi: https://doi.org/10.1242/dmm.010389
Brunet, A., Bonni, A., Zigmond, M. J., Lin, M. Z., Juo, P., Hu, L. S., . . . Greenberg, M. E. (1999). Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell, 96(6), 857-868. doi: https://doi.org/10.1016/S0092-8674(00)80595-4
Desplanches, D., Mayet, M. H., Sempore, B., & Flandrois, R. (1987). Structural and functional responses to prolonged hindlimb suspension in rat muscle. J Appl Physiol (1985), 63(2), 558-563. doi: https://doi.org/10.1152/jappl.1987.63.2.558
Ebert, S. M., Dyle, M. C., Kunkel, S. D., Bullard, S. A., Bongers, K. S., Fox, D. K., . . . Adams, C. M. (2012). Stress-induced skeletal muscle Gadd45a expression reprograms myonuclei and causes muscle atrophy. J Biol Chem, 287(33), 27290-27301. doi: https://doi.org/10.1074/jbc.M112.374777
Ebert, S. M., Monteys, A. M., Fox, D. K., Bongers, K. S., Shields, B. E., Malmberg, S. E., . . . Adams, C. M. (2010). The transcription factor ATF4 promotes skeletal myofiber atrophy during fasting. Molecular Endocrinology, 24(4), 790-799. doi: https://doi.org/10.1210/me.2009-0345
Edwards, M. G., Anderson, R. M., Yuan, M., Kendziorski, C. M., Weindruch, R., & Prolla, T. A. (2007). Gene expression profiling of aging reveals activation of a p53-mediated transcriptional program. BMC Genomics, 8(1), 80. doi: https://doi.org/10.1186/1471-2164-8-80
Ehrnhoefer, D. E., Skotte, N. H., Ladha, S., Nguyen, Y. T., Qiu, X., Deng, Y., . . . Becanovic, K. (2013). p53 increases caspase-6 expression and activation in muscle tissue expressing mutant huntingtin. Human Molecular Genetics, 23(3), 717-729.  doi: https://doi.org/10.1093/hmg/ddt458
Evans, W. J. (2010). Skeletal muscle loss: Cachexia, sarcopenia, and inactivity. Am J Clin Nutr, 91(4), 1123s-1127s. doi: https://doi.org/10.3945/ajcn.2010.28608A
Foletta, V. C., White, L. J., Larsen, A. E., Leger, B., & Russell, A. P. (2011). The role and regulation of MAFbx/atrogin-1 and MuRF1 in skeletal muscle atrophy. Pflugers Arch, 461(3), 325-335. doi: https://doi.org/10.1007/s00424-010-0919-9
Fox, D. K., Ebert, S. M., Bongers, K. S., Dyle, M. C., Bullard, S. A., Dierdorff, J. M., . . . Adams, C. M. (2014). p53 and ATF4 mediate distinct and additive pathways to skeletal muscle atrophy during limb immobilization. American Journal of Physiology-Endocrinology and Metabolism, 307(3), E245-E261. doi: https://doi.org/10.1152/ajpendo.00010.2014
Fox, D. K., Ebert, S. M., Bongers, K. S., Dyle, M. C., Bullard, S. A., Dierdorff, J. M., . . . Adams, C. M. (2014). p53 and ATF4 mediate distinct and additive pathways to skeletal muscle atrophy during limb immobilization. Am J Physiol Endocrinol Metab, 307(3), E245-261. doi: https://doi.org/10.1152/ajpendo.00010.2014
Giger, J. M., Bodell, P. W., Zeng, M., Baldwin, K. M., & Haddad, F. (2009). Rapid muscle atrophy response to unloading: pretranslational processes involving MHC and actin. J Appl Physiol (1985), 107(4), 1204-1212. doi: https://doi.org/10.1152/japplphysiol.00344.2009
Gomes, M. D., Lecker, S. H., Jagoe, R. T., Navon, A., & Goldberg, A. L. (2001). Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proceedings of the National Academy of Sciences, 98(25), 14440-14445. doi: https://doi.org/10.1073/pnas.251541198
 Gordon, B. S., Kelleher, A. R., & Kimball, S. R. (2013). Regulation of muscle protein synthesis and the effects of catabolic states. Int J Biochem Cell Biol, 45(10), 2147-2157. doi: https://doi.org/10.1016/j.biocel.2013.05.039
Herbison, G. J., Jaweed, M. M., & Ditunno, J. F. (1979). Muscle atrophy in rats following denervation, casting, inflammation, and tenotomy. Arch Phys Med Rehabil, 60(9), 401-404. PMID: 496606
Horn, H., & Vousden, K. (2007). Coping with stress: Multiple ways to activate p53. Oncogene, 26(9), 1306.  doi: https://doi.org/10.1038/sj.onc.1210263
Horn, H. F., & Vousden, K. H. (2007). Coping with stress: Multiple ways to activate p53. Oncogene, 26(9), 1306-1316. doi: https://doi.org/10.1038/sj.onc.1210263
Hughes, D. C., Marcotte, G. R., Marshall, A. G., West, D. W., Baehr, L. M., Wallace, M. A., . . . Baar, K. (2016). Age-related differences in dystrophin: Impact on force transfer proteins, membrane integrity, and neuromuscular junction stability. Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 72(5), 640-648. doi: https://doi.org/10.1093/gerona/glw109
 Keller, K., & Engelhardt, M. (2013). Strength and muscle mass loss with aging process. Age and strength loss. Muscles, Ligaments and Tendons Journal, 3(4), 346-350. PMID: 24596700
Kyparos, A., Feeback, D. L., Layne, C. S., Martinez, D. A., & Clarke, M. S. (2005). Mechanical stimulation of the plantar foot surface attenuates soleus muscle atrophy induced by hindlimb unloading in rats. J Appl Physiol (1985), 99(2), 739-746. doi: https://doi.org/10.1152/japplphysiol.00771.2004
Li, P., Waters, R. E., Redfern, S. I., Zhang, M., Mao, L., Annex, B. H., & Yan, Z. (2007). Oxidative phenotype protects myofibers from pathological insults induced by chronic heart failure in mice. The American Journal of Pathology, 170(2), 599-608. doi: https://doi.org/10.2353/ajpath.2007.060505
Milan, G., Romanello, V., Pescatore, F., Armani, A., Paik, J.-H., Frasson, L., . . . Goldberg, A. L. (2015). Regulation of autophagy and the ubiquitin–proteasome system by the FoxO transcriptional network during muscle atrophy. Nature Communications, 6, 6670.  doi: https://doi.org/10.1038/ncomms7670
Ohira, Y., Kawano, F., Wang, X., Sudoh, M., Iwashita, Y., Majima, H., & Nonaka, I. (2006). Irreversible morphological changes in leg bone following chronic gravitational unloading of growing rats. Life Sciences, 79(7), 686-694. doi: https://doi.org/10.1016/j.lfs.2006.02.022
Ohira, Y., Nomura, T., Kawano, F., Sato, Y., Ishihara, A., & Nonaka, I. (2002). Effects of nine weeks of unloading on neuromuscular activities in adult rats. Journal of Gravitational Physiology: A Journal of the International Society for Gravitational Physiology, 9(2), 49-59. PMID: 14638459
Parrini, M., Ghezzi, D., Deidda, G., Medrihan, L., Castroflorio, E., Alberti, M., . . . Contestabile, A. (2017). Aerobic exercise and a BDNF-mimetic therapy rescue learning and memory in a mouse model of Down syndrome. Scientific Reports, 7(1), 16825. doi: https://doi.org/10.1038/s41598-017-17201-8
Rodriguez, J., Vernus, B., Chelh, I., Cassar-Malek, I., Gabillard, J. C., Hadj Sassi, A., . . . Bonnieu, A. (2014). Myostatin and the skeletal muscle atrophy and hypertrophy signaling pathways. Cell Mol Life Sci, 71(22), 4361-4371. doi: https://doi.org/10.1007/s00018-014-1689-x
Sacheck, J. M., Hyatt, J. P., Raffaello, A., Jagoe, R. T., Roy, R. R., Edgerton, V. R., . . . Goldberg, A. L. (2007). Rapid disuse and denervation atrophy involve transcriptional changes similar to those of muscle wasting during systemic diseases. Faseb j, 21(1), 140-155. doi: https://doi.org/10.1096/fj.06-6604com
Sandri, M. (2010). Autophagy in skeletal muscle. FEBS Lett, 584(7), 1411-1416. doi: https://doi.org/10.1016/j.febslet.2010.01.056
Sandri, M., Sandri, C., Gilbert, A., Skurk, C., Calabria, E., Picard, A., . . . Goldberg, A. L. (2004). Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell, 117(3), 399-412.  doi: https://doi.org/10.1016/s0092-8674(04)00400-3
Schwarzkopf, M., Coletti, D., Marazzi, G., & Sassoon, D. (2008). Chronic p53 activity leads to skeletal muscle atrophy and muscle stem cell perturbation. Basic Appl Myol, 18(5), 131-138.
Stephens, N. A., Gallagher, I. J., Rooyackers, O., Skipworth, R. J., Tan, B. H., Marstrand, T., . . . Fearon, K. C. (2010). Using transcriptomics to identify and validate novel biomarkers of human skeletal muscle cancer cachexia. Genome Medicine, 2(1), 1.  doi: https://doi.org/10.1186/gm122
Stitt, T. N., Drujan, D., Clarke, B. A., Panaro, F., Timofeyva, Y., Kline, W. O., . . . Glass, D. J. (2004). The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol Cell, 14(3), 395-403. doi: https://doi.org/10.1016/S1097-2765(04)00211-4
Thomason, D. B., & Booth, F. W. (1990). Atrophy of the soleus muscle by hindlimb unweighting. J Appl Physiol (1985), 68(1), 1-12. doi: https://doi.org/10.1152/jappl.1990.68.1.1
Tiao, G., Lieberman, M., Fischer, J., & Hasselgren, P. (1997). Intracellular regulation of protein degradation during sepsis is different in fast-and slow-twitch muscle. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 272(3), R849-R856.  doi: https://doi.org/10.1152/ajpregu.1997.272.3.R849
Tiao, G., Lieberman, M., Fischer, J. E., & Hasselgren, P. O. (1997). Intracellular regulation of protein degradation during sepsis is different in fast- and slow-twitch muscle. Am J Physiol, 272(3 Pt 2), R849-856. doi: https://doi.org/10.1152/ajpregu.1997.272.3.R849
Tsika, R. W., Herrick, R. E., & Baldwin, K. M. (1987). Effect of anabolic steroids on skeletal muscle mass during hindlimb suspension. J Appl Physiol (1985), 63(5), 2122-2127. doi: https://doi.org/10.1152/jappl.1987.63.5.2122
Ura, S., Masuyama, N., Graves, J. D., & Gotoh, Y. (2001). Caspase cleavage of MST1 promotes nuclear translocation and chromatin condensation. Proceedings of the National Academy of Sciences of the United States of America, 98(18), 10148-10153. doi: https://doi.org/10.1073/pnas.181161698
Verdijk, L. B., Dirks, M. L., Snijders, T., Prompers, J. J., Beelen, M., Jonkers, R. A., . . . Van Loon, L. J. (2012). Reduced satellite cell numbers with spinal cord injury and aging in humans. Med Sci Sports Exerc, 44(12), 2322-2330. doi: https://doi.org/10.1249/MSS.0b013e3182667c2e
Verhees, K. J., Schols, A. M., Kelders, M. C., Op den Kamp, C. M., van der Velden, J. L., & Langen, R. C. (2011). Glycogen synthase kinase-3beta is required for the induction of skeletal muscle atrophy. Am J Physiol Cell Physiol, 301(5), C995-c1007. doi: https://doi.org/10.1152/ajpcell.00520.2010
Wei, B., Dui, W., Liu, D., Xing, Y., Yuan, Z., & Ji, G. (2013a). MST1, a key player, in enhancing fast skeletal muscle atrophy. BMC Biology, 11(1), 12.  doi: https://doi.org/10.1186/1741-7007-11-12
 Wei, B., Dui, W., Liu, D., Xing, Y., Yuan, Z., & Ji, G. (2013b). MST1, a key player, in enhancing fast skeletal muscle atrophy. BMC Biology, 11, 12-12. doi: https://doi.org/10.1186/1741-7007-11-12
Yu, Z., Li, P., Zhang, M., Hannink, M., Stamler, J. S., & Yan, Z. (2008). Fiber type-specific nitric oxide protects oxidative myofibers against cachectic stimuli. PloS one, 3(5), e2086.  doi: https://doi.org/10.1371/journal.pone.0002086
Zhang, B. T., Yeung, S. S., Liu, Y., Wang, H. H., Wan, Y. M., Ling, S. K., . . . Yeung, E. W. (2010). The effects of low frequency electrical stimulation on satellite cell activity in rat skeletal muscle during hindlimb suspension. BMC Cell Biol, 11, 87. doi: https://doi.org/10.1186/1471-2121-11-87
Zhang, Q. W., Li, G. Y., Ren, Y. P., & Gao, Y. F. (2015). [Effect of two Pi deficiency syndrome models on the configuration and function of the skeletal muscle in mice]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 35(1), 71-75. PMID: 25790678
 
 
 
Volume 1, Issue 3
December 2021
Pages 124-132
  • Receive Date: 30 September 2021
  • Revise Date: 22 November 2021
  • Accept Date: 19 December 2021
  • First Publish Date: 19 December 2021