{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T10:09:40Z","timestamp":1782122980232,"version":"3.54.5"},"reference-count":54,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2016,5,13]],"date-time":"2016-05-13T00:00:00Z","timestamp":1463097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education and Research of the Republic of Estonia","award":["TMUSF14058I"],"award-info":[{"award-number":["TMUSF14058I"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Muscle weakness in corticosteroid myopathy is mainly the result of the destruction and atrophy of the myofibrillar compartment of fast-twitch muscle fibers. Decrease of titin and myosin, and the ratio of nebulin and MyHC in myopathic muscle, shows that these changes of contractile and elastic proteins are the result of increased catabolism of the abovementioned proteins in skeletal muscle. Slow regeneration of skeletal muscle is in good correlation with a decreased number of satellite cells under the basal lamina of muscle fibers. Aging causes a reduction of AMP-activated protein kinase (AMPK) activity as the result of the reduced function of the mitochondrial compartment. AMPK activity increases as a result of increased functional activity. Resistance exercise causes anabolic and anticatabolic effects in skeletal muscle: muscle fibers experience hypertrophy while higher myofibrillar proteins turn over. These changes are leading to the qualitative remodeling of muscle fibers. As a result of these changes, possible maximal muscle strength is increasing. Endurance exercise improves capillary blood supply, increases mitochondrial biogenesis and muscle oxidative capacity, and causes a faster turnover rate of sarcoplasmic proteins as well as qualitative remodeling of type I and IIA muscle fibers. The combination of resistance and endurance exercise may be the fastest way to prevent or decelerate muscle atrophy due to the anabolic and anticatabolic effects of exercise combined with an increase in oxidative capacity. The aim of the present short review is to assess the role of myofibrillar protein catabolism in the development of glucocorticoid-caused myopathy from aging and physical activity aspects.<\/jats:p>","DOI":"10.3390\/metabo6020015","type":"journal-article","created":{"date-parts":[[2016,5,13]],"date-time":"2016-05-13T11:53:16Z","timestamp":1463140396000},"page":"15","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Role of Myofibrillar Protein Catabolism in Development of Glucocorticoid Myopathy: Aging and Functional Activity Aspects"],"prefix":"10.3390","volume":"6","author":[{"given":"Teet","family":"Seene","sequence":"first","affiliation":[{"name":"Institute of Sport Sciences and Physiotherapy, University of Tartu, Ravila 14a, Tartu 50411, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priit","family":"Kaasik","sequence":"additional","affiliation":[{"name":"Institute of Sport Sciences and Physiotherapy, University of Tartu, Ravila 14a, Tartu 50411, Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0960-0760(94)90165-1","article-title":"Turnover of skeletal muscle contractile proteins in glucocorticoid myopathy","volume":"50","author":"Seene","year":"1994","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lehmann, M., Foster, C., Gastmann, U., Keizer, H., and Steinacker, J. (1999). Overload, Performance Incompentence, and Regeneration in Sport, Kluwer Academic\/Plenum Publishers.","DOI":"10.1007\/b102418"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/0002-9343(76)90327-2","article-title":"Steroid myopathy in connective tissue disease","volume":"61","author":"Askari","year":"1976","journal-title":"Am. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3217","DOI":"10.1016\/S0021-9258(18)93116-9","article-title":"Protein turnover in skeletal muscle in experimental corticosteroid myopathy","volume":"244","author":"Goldberg","year":"1969","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1042\/bj1780139","article-title":"Effect of glucocorticoid administration on the rate of muscle protein breakdown in vivo in rats, as measured by urinary excretion on N-methylhistidine","volume":"178","author":"Tomas","year":"1979","journal-title":"Biochem. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5","DOI":"10.5455\/jihp.20120606081246","article-title":"Fine architectonics and protein turnover rate in myofibrils of glucocorticoid caused myopathic rats","volume":"1","author":"Kaasik","year":"2012","journal-title":"J. Interdiscip. Histopathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/0022-4731(82)90190-X","article-title":"The catabolic effect of glucocorticoids on different types of skeletal muscle fibres and its dependence upon muscle activity and interaction with anabolic steroids","volume":"16","author":"Seene","year":"1982","journal-title":"J. Steroid Biochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1042\/bj2080593","article-title":"Effect of corticosterone on myofibrillar protein turnover in diabetic rat as assessed by N-methylhistidine excretion","volume":"208","author":"Tomas","year":"1982","journal-title":"Biochem. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/0022-4731(85)90284-5","article-title":"Effect of glucocorticoids on the turnover rate of actin and myosin heavy chains on different types of skeletal muscle fibres","volume":"22","author":"Seene","year":"1985","journal-title":"J. Steroid Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/0022-4731(88)90032-5","article-title":"Effect of glucocorticoids on contractile apparatus of rat skeletal muscle","volume":"29","author":"Seene","year":"1988","journal-title":"J. Steroid Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.jsbmb.2003.08.002","article-title":"The effect of glucocorticoids on the myosin heavy chain isoforms\u2019 turnover in skeletal muscle","volume":"86","author":"Seene","year":"2003","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"70","DOI":"10.4236\/abc.2013.31009","article-title":"Glucocorticoid-induced alterations in titin, nebulin, myosin heavy chain isoform content and viscosoelastic properties of rat skeletal muscle","volume":"3","author":"Aru","year":"2013","journal-title":"Adv. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/0047-6374(91)90131-I","article-title":"Skeletal muscle atrophy in old rats: Defferential changes in three fiber types","volume":"60","author":"Holloszy","year":"1991","journal-title":"Mech. Ageing Dev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1016\/j.biocel.2005.04.009","article-title":"Altered responses in skeletal muscle protein turnover during aging in anabolic and catabolic periods","volume":"37","author":"Attaix","year":"2005","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.jsbmb.2006.11.024","article-title":"Ageing and dexamethasone associated sarcopenia: Peculiarities of regeneration","volume":"105","author":"Kaasik","year":"2007","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"126","DOI":"10.2174\/1874609811205020126","article-title":"Aging and regenerative capacity of skeletal muscle in rats","volume":"5","author":"Kaasik","year":"2012","journal-title":"Curr. Aging Sci."},{"key":"ref_17","first-page":"E226","article-title":"Partial prevention of glucocorticoid induced muscle atrophy by endurance training","volume":"241","author":"Hickson","year":"1981","journal-title":"Am. J. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"172492","DOI":"10.1155\/2012\/172492","article-title":"Role of exercise therapy in prevention of decline in aging muscle function: Glucocorticoid myopathy and unloading","volume":"2012","author":"Seene","year":"2012","journal-title":"J. Aging Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1210\/jcem-45-2-240","article-title":"Plasma testosterone profiles in cushing\u2019s syndrome","volume":"45","author":"Smals","year":"1977","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/mus.880090102","article-title":"A morphological (biochemical) study on the action of corticosteroids on rat skeletal muscle","volume":"9","author":"Kelly","year":"1986","journal-title":"Muscle Nerve"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2686","DOI":"10.1271\/bbb.64.2686","article-title":"Effects of cortiosterone on connection content and protein breakdown in rat skeletal muscle","volume":"64","author":"Hayashi","year":"2000","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1152\/jappl.1987.63.4.1504","article-title":"Initiating regular exercise protects against muscle atrophy from glucocorticoids","volume":"63","author":"Czerwinski","year":"1987","journal-title":"J. Appl. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2945","DOI":"10.1210\/endo.141.8.7621","article-title":"Dexamethasone inhibits insulin-like growth factor signaling and potentiates myoblast apoptosis","volume":"14","author":"Singleton","year":"2000","journal-title":"Endocrinology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.jsbmb.2003.11.012","article-title":"Skeletal muscle: a dual system to measure glucocorticoid\u2014Dependent transactivation and transrepression of gene regulation","volume":"88","author":"Pandit","year":"2004","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Flack, K., Davy, K., Hulver, M., Winett, R., Friasrd, M., and Davy, B. (2011). Aging, resistance training, and diabetes prevention. J. Aging Res.","DOI":"10.4061\/2011\/127315"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1113\/jphysiol.2008.164087","article-title":"Differential stimulation of myofibrillar and sarcoplasmic protein synthesis with protein ingestion at rest and after resistance exercise","volume":"587","author":"Moore","year":"2009","journal-title":"J. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/j.1748-1716.2010.02187.x","article-title":"Resistance exercise enhances mTOR and MAPK signalling in human muscle over that seen at rest after bolus protein ingestion","volume":"201","author":"Moore","year":"2011","journal-title":"Acta Physiol. (Oxf.)"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1123\/japa.16.1.97","article-title":"The effect of aging on skeletal-muscle recovery from exercise: Possible implications for aging athletes","volume":"16","author":"Fell","year":"2008","journal-title":"J. Aging Phys. Act."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1113\/jphysiol.1988.sp017279","article-title":"Contractile properties of skeletal muscles from young, adult, and aged mice","volume":"404","author":"Brooks","year":"1988","journal-title":"J. Physiol."},{"key":"ref_30","first-page":"185","article-title":"Ultrastructural changes in the skeletal muscle of senile rats with significant age-dependent motor deficit","volume":"8","author":"Kaminska","year":"1998","journal-title":"Basic Appl. Myol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/j.1749-6632.1998.tb09894.x","article-title":"Age-associated changes in the response of skeletal muscle cells to exercise and regeneration","volume":"854","author":"Grounds","year":"1998","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"B224","DOI":"10.1093\/gerona\/56.5.B224","article-title":"Skeletal muscle regeneration in very old rats","volume":"56","author":"Carlson","year":"2001","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1172\/JCI118264","article-title":"Sensitivity and protein turnover response to glucocorticoids are different in skeletal muscle from adult and old rats. Lack of regulation of the ubiquitin-proteasome proteolytic pathway in ageing","volume":"96","author":"Dardevet","year":"1995","journal-title":"J. Clin. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1677\/joe.0.1560083","article-title":"Glucocorticoid effects on insulin and IGF-1-regulated muscle protein metabolism during aging","volume":"156","author":"Dardevet","year":"1998","journal-title":"J. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1152\/japplphysiol.00437.2003","article-title":"Age-related changes in the mitotic and metabolic characteristics of muscle-derived cells","volume":"95","author":"Barani","year":"2003","journal-title":"J. Appl. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1016\/j.exger.2004.08.009","article-title":"Increased nuclear proteins in muscle satellite cells in aged animals as compared to young growing animals","volume":"39","author":"Machida","year":"2004","journal-title":"Exp. Gerontol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1126\/science.1079161","article-title":"Aging and genome maintenance: Lessons from the mouse?","volume":"299","author":"Hasty","year":"2003","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1196\/annals.1297.073","article-title":"Alpha lipoic acid\u2019s role in delaying the mitochondrial decay of aging","volume":"1019","author":"Ames","year":"2004","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.archger.2011.05.002","article-title":"Review on aging, unloading and reloading: Changes in skeletal muscle quantity and quality","volume":"54","author":"Seene","year":"2012","journal-title":"Arch. Gerontol. Geriatr."},{"key":"ref_40","first-page":"124","article-title":"Changes in fast-twitch muscle oxidative capacity and myosin isoforms modulation during endurance training","volume":"47","author":"Seene","year":"2007","journal-title":"J. Sports Med. Phys. Fitness"},{"key":"ref_41","first-page":"410","article-title":"Structural rearrangements in contractile apparatus and resulting skeletal muscle remodelling: Effect of exercise training","volume":"49","author":"Seene","year":"2009","journal-title":"J. Sports Med. Phys. Fitness"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/s11102-008-0098-2","article-title":"The pituitary-adrenal axis and body composition","volume":"12","author":"Stewart","year":"2009","journal-title":"Pituitary"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Pette, D. (1990). The Dynamics State of Muscle Fibers, Walter de Gruyter.","DOI":"10.1515\/9783110884784"},{"key":"ref_44","first-page":"137","article-title":"Myosin heavy chain composition in regulating skeletal muscle grafts","volume":"7","author":"Alev","year":"1997","journal-title":"Basic Appl. Myol."},{"key":"ref_45","first-page":"160","article-title":"Signaling in muscle atrophy and hypertrophy","volume":"23","author":"Sandri","year":"2008","journal-title":"Physiology (Bethesda)"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.cmet.2011.01.001","article-title":"Crosstalk between glucocorticoid receptor and nutritional sensor mTOR in skeletal muscle","volume":"13","author":"Shimizu","year":"2011","journal-title":"Cell Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s13539-011-0052-4","article-title":"Sarcopenia and cachexia: The adaptations of negative regulators of skeletal muscle mass","volume":"3","author":"Sakuma","year":"2012","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s13539-011-0025-7","article-title":"Myopenia\u2014A new unviversal term for muscle wasting","volume":"2","author":"Fearon","year":"2011","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.jamda.2014.09.007","article-title":"Treatment of cachexia: An overview of recent developments","volume":"15","author":"Anker","year":"2014","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s13539-014-0135-0","article-title":"Muscle wasting disease: A proposal for a new disease classification","volume":"5","author":"Anker","year":"2014","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1056\/NEJMcibr1106880","article-title":"Cancer cachexia and fat\u2014Muscle physiology","volume":"365","author":"Fearon","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.cmet.2007.01.008","article-title":"Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis","volume":"5","author":"Reznick","year":"2007","journal-title":"Cell Metab."},{"key":"ref_53","first-page":"E299","article-title":"Inactivation of acetyl-CoA carboxylase and activation of AMP\u2014Activated protein kinase in muscle during exercis","volume":"270","author":"Winder","year":"1996","journal-title":"Am. J. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/ncb839","article-title":"TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling","volume":"4","author":"Inoki","year":"2002","journal-title":"Nat. Cell Biol."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/6\/2\/15\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:23:49Z","timestamp":1760210629000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/6\/2\/15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,13]]},"references-count":54,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2016,6]]}},"alternative-id":["metabo6020015"],"URL":"https:\/\/doi.org\/10.3390\/metabo6020015","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,13]]}}}