Skip to main content

Advertisement

Log in

Reactive oxygen species play a role in muscle wasting during thyrotoxicosis

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

The role of reactive oxygen species (ROS) in muscle protein hydrolysis and protein oxidation in thyrotoxicosis has not been explored. This study indicates that ROS play a role in skeletal muscle wasting pathways in thyrotoxicosis. Two experimental groups (rats) were treated for 5 days with either 3,3′,5-triiodothyronine (HT) or HT with α-tocopherol (HT + αT). Two controls were used, vehicle (Control) and control treated with αT (Control + αT). Serum T3, peritoneal fat, serum glycerol, muscle and body weight, temperature, mitochondrial metabolism (cytochrome c oxidase activity), oxidative stress parameters and proteolytic activities were examined. High body temperature induced by HT returned to normal when animals were treated with αT, although total body and muscle weight did not. An increase in lipolysis was observed in the HT + αT group, as peritoneal fat decreased significantly together with an increase in serum glycerol. GSH, GSSG and total radical-trapping antioxidant parameter (TRAP) decreased and catalase activity increased in the HT group. The glutathione redox ratio was higher in HT + αT than in both HT and Control + αT groups. Carbonyl proteins, AOPP, mitochondrial and chymotrypsin-like proteolytic activities were higher in the HT group than in the Control. HT treatment with αT restored mitochondrial metabolism, TRAP, carbonyl protein, chymotrypsin-like activity and AOPP to the level as that of the Control + αT. Calpain activity was lower in the HT + αT group than in HT and Control + αT and superoxide dismutase (SOD) activity was higher in the HT + αT group than in the Control + αT. Although αT did not reverse muscle loss, ROS was involved in proteolysis to some degree.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

αT:

Alpha-tocopherol

BSA:

Bovine serum albumin

Control+αT:

Control treated with αT

DNPH:

2,4-dinitrophenylhydrazine

EDTA:

Ethylenediamine tetraacetic acid

GSSG:

Oxidized glutathione

GSH:

Reduced glutathione

HT:

Hormone treated

HT+αT:

Hormone treated plus αT treatment

IM:

Isolation medium

KI:

Potassium iodide

MDA:

Malondialdehyde

RLU:

Relative light units

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

T3:

3,3′,5-triiodothyronine

TBARS:

Thiobarbituric acid-reactive substances

TCA:

Trichloroacetic acid

References

  • Adams J (2002) Development of the proteasome inhibitor PS-341. Oncologist 7:9–16

    Article  CAS  PubMed  Google Scholar 

  • Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  CAS  PubMed  Google Scholar 

  • Angerås U, Hasseigren PO (1985) Protein turnover in different types of skeletal muscle during experimental hyperthyroidism in rats. Acta Endocrinol 109:90–95

    PubMed  Google Scholar 

  • Asayama K, Dobashi K, Hayashibe H, Kato K (1989) Vitamin E protects against thyroxine-induced acceleration of lipid peroxidation in cardiac and skeletal muscles in rats. J Nutr Sci Vitaminol 35:407–418

    Article  CAS  PubMed  Google Scholar 

  • Asayama K, Kato K (1990) Oxidative muscular injury and its relevance to hyperthyroidism. Free Radic Biol Med 8:293–303

    Article  CAS  PubMed  Google Scholar 

  • Barker T, Traber MG (2007) From animals to humans: evidence linking oxidative stress as a causative factor in muscle atrophy. J Physiol 583:421–422

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bartoli M, Richard I (2005) Calpains in muscle wasting. Int J Biochem Cell Biol 37:2115–2133

    Article  CAS  PubMed  Google Scholar 

  • Cakatay U, Telci A, Kayali R, Tekeli F, Akçay T, Sivas A (2003) Relation of aging with oxidative protein damage parameters in the rat skeletal muscle. Clin Biochem 36:51–55

    Article  CAS  PubMed  Google Scholar 

  • Carter W, Benjamin W, Faas F (1982) Effects of experimental hyperthyroidism on protein turnover in skeletal and cardiac muscle as measured by [14C] tyrosine infusion. Biochem J 204:69–74

    CAS  PubMed Central  PubMed  Google Scholar 

  • Carter WJ, van der Weijden Benjamin WS, Faas F (1981) Effect of experimental hyperthyroidism on skeletal-muscle proteolysis. Biochem J 194:685–690

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cassina A, Radi R (1996) Differential inhibitory action of nitric oxide and peroxynitrite on mitochondrial electron transport. Arch Biochem Biophys 328:309–316

    Article  CAS  PubMed  Google Scholar 

  • Cooper DS, Greenspan FS, Ladenson PW (2007) The thyroid gland. In: Gardner DG, Shoback DM (eds) Greenspan’s - Basic & Clinical Endocrinology, 8th edn. McGraw-Hill, New York, pp 209–267

    Google Scholar 

  • Cunha NV, de Abreu SB, Panis C, Grassiolli S, Guarnier FA, Cecchini R, Mazzuco TL, Pinge-Filho P, Martins-Pinge MC (2010) Cox-2 inhibition attenuates cardiovascular and inflammatory aspects in monosodium glutamate-induced obese rats. Life Sci 87:375–381

    Article  CAS  PubMed  Google Scholar 

  • Davies TF, Larsen PR (2002) Thyrotoxicosis. In: Larsen PR, Kronenberg HM, Melmed S, Polonsky KS (eds) Williams Textbook of Endocrinology, vol 10. Elsevier, Philadelphia, pp 374–422

    Google Scholar 

  • Diano S (2013) Role of Reactive Oxygen Species in Hypothalamic Regulation of Energy Metabolism. Endocrinol Metab 28:3–5

    Article  Google Scholar 

  • Fermoselle C, Rabinovich R, Ausín P, Puig-Vilanova E, Coronell C, Sanchez F, Roca J, Gea J, Barreiro E (2012) Does oxidative stress modulate limb muscle atrophy in severe COPD patients? Eur Respir J 40(4):851–862

    Article  CAS  PubMed  Google Scholar 

  • Gille L, Staniek K, Rosenau T, Duvigneau JC, Kozlov AV (2010) Tocopheryl quinones and mitochondria. Mol Nutr Food Res 54:601–615

    Article  CAS  PubMed  Google Scholar 

  • Glickman MH, Ciechanover A (2002) The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev 82:373–428

    CAS  PubMed  Google Scholar 

  • Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL (2001) Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad USA 98(25):14440–14445

    Article  CAS  Google Scholar 

  • Gredilla R, López Torres M, Portero-Otín M, Pamplona R, Barja G (2001) Influence of hyper‐and hypothyroidism on lipid peroxidation, unsaturation of phospholipids, glutathione system and oxidative damage to nuclear and mitochondrial DNA in mice skeletal muscle. Mol Cell Biochem 221:41–48

    Article  CAS  PubMed  Google Scholar 

  • Guarnier FA, Cecchini AL, Suzukawa AA, Maragno AL, Simão AN, Gomes MD, Cecchini R (2010) Time course of skeletal muscle loss and oxidative stress in rats with walker 256 solid tumor. Muscle Nerve 42:950–958

    Article  CAS  PubMed  Google Scholar 

  • Halliwell B, Gutteridge JMC (2007) Free radicals in biology and medicine. Oxford University Press, New York

    Google Scholar 

  • Hershko A, Ciechanover A (1998) The ubiquitin system. Annu Rev Biochem 67:425–479

    Article  CAS  PubMed  Google Scholar 

  • Horak HA, Pourmand R (2000) Endocrine myophaties. Neurol Clin 18:203–213

    Article  CAS  PubMed  Google Scholar 

  • Isermann B, Bierhaus A, Tritschler H, Ziegler R, Nawroth PP (1999) alpha-Tocopherol induces leptin expression in healthy individuals and in vitro. Diabetes Care 22:1227–1228

    Article  CAS  PubMed  Google Scholar 

  • Jahngen-Hodge J, Obin MS, Gong X, Shang F, Nowell TR Jr, Gong J, Abasi H, Blumberg J, Taylor A (1997) Regulation of ubiquitin-conjugating enzymes by glutathione following oxidative stress. J Biol Chem 272:28218–28226

    Article  CAS  PubMed  Google Scholar 

  • Korkmaz GG, Altınoglu E, Civelek S, Sozer V, Erdenen F, Tabak O, Uzun H (2013) The association of oxidative stress markers with conventional risk factors in the metabolic syndrome. Metabolism 62:828–835

    Article  CAS  PubMed  Google Scholar 

  • Lass A, Sohal RS (2000) Effect of coenzyme Q10 and α-tocopherol content of mitochondria on the production of superoxide anion radicals. FASEB J 14:87–94

    CAS  PubMed  Google Scholar 

  • Li D, Saldeen T, Romeo F, Mehta JL (1999) Relative effects of alpha- and gamma-tocopherol on low-density lipoprotein oxidation and superoxide dismutase and nitric oxide synthase activity and protein expression in rats. J Cardiovasc Pharmacol Ther 4:219–226

    Article  CAS  PubMed  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  • Lucy JA (1978) Structural interactions between vitamin E and polyunsaturated phospholipids. In: de Duve C, Hayaishi O (eds) Tocopherol. Oxygen and Biomembranes. Elsevier, Amsterdam, pp 109–120

    Google Scholar 

  • Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474

    Article  CAS  PubMed  Google Scholar 

  • Mastrocola R, Reffo P, Penna F, Tomasinelli CE, Boccuzzi G, Baccino FM, Aragno M, Costelli P (2008) Muscle wasting in diabetic and in tumor-bearing rats: role of oxidative stress. Free Radic Bio Med 44:584–593

    Article  CAS  Google Scholar 

  • Miller G (1959) Protein determination of large numbers of samples. Anal Chem 31:964

    Article  CAS  Google Scholar 

  • Mittra ES, Niederkohr RD, Rodriguez C, El-Maghraby T, McDougall IR (2008) Uncommon causes of thyrotoxicosis. J Nucl Med 49:265–278

    Article  PubMed  Google Scholar 

  • Morrison WL, Gibson JN, Jung RT, Rennie MJ (1988) Skeletal muscle and whole body protein turnover in thyroid disease. Eur J Clin Investig 18:62–68

    Article  CAS  Google Scholar 

  • Németh I, Boda D (1989) The ratio of oxidized/reduced glutathione as an index of oxidative stress in various experimental models of shock syndrome. Biomed Biochim Acta 48:S53–S57

    PubMed  Google Scholar 

  • Nicol CJM, Bruce DS (1981) Effect of hyperthyroidism on the contractile and histochemical properties of fast and slow twitch skeletal muscle in the rat. Pflugers Arch Eur J Physiol 390:73–79

    Article  CAS  Google Scholar 

  • Nørrelund H, Hove KY, Brems-Dalgaard E, Jurik AG, Nielsen LP, Nielsen S, Jørgensen JO, Weeke J, Møller N (1999) Muscle mass and function in thyrotoxic patients before and during medical treatment. Clin Endocrinol 51:693–699

    Article  Google Scholar 

  • Nurjhan N, Kennedy F, Consoli A, Martin C, Miles J, Gerich J (1988) Quantification of the glycolytic origin of plasma glycerol: implications for the use of the rate of appearance of plasma glycerol as an index of lipolysis in vivo. Metabolism 37:386–389

    Article  CAS  PubMed  Google Scholar 

  • Oliveira FJA, Cecchini R (2000) Oxidative stress of liver in hamsters infected with Leishmania (L.) chagasi. J Parasitol 86:1067–1072

    Article  CAS  PubMed  Google Scholar 

  • O'Neal P, Alamdari N, Smith I, Poylin V, Menconi M, Hasselgren PO (2009) Experimental hyperthyroidism in rats increases the expression of the ubiquitin ligases atrogin‐1 and MuRF1 and stimulates multiple proteolytic pathways in skeletal muscle. J Cell Biochem 108:963–973

    Article  PubMed  Google Scholar 

  • Oppenheimer JH, Schwartz HL, Lane JT, Thompson MP (1991) Functional relationship of thyroid hormone-induced lipogenesis, lipolysis, and thermogenesis in the rat. J Clin Invest 87:125–132

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ory RL, Altschul AM (1962) Participation of tocopherol derivatives in lipolysis. Biochem Biophys Res Commun 7:370–374

    Article  CAS  PubMed  Google Scholar 

  • Pellegrino MA, Desaphy JF, Brocca L, Pierno S, Camerino DC, Bottinelli R (2011) Redox homeostasis, oxidative stress and disuse muscle atrophy. J Physiol 589:2147–2160

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Powers SK (2009) Calpain and caspase-3 are required for sepsis-induced diaphragmatic weakness. J Appl Physiol 107:1369

    Article  PubMed  Google Scholar 

  • Powers SK, Kavazis AN, McClung JM (2007) Oxidative stress and disuse muscle atrophy. J Appl Physiol 102:2389–2397

    Article  CAS  PubMed  Google Scholar 

  • Powers SK, Duarte J, Kavazis AN, Talbert EE (2010) Reactive oxygen speciesare signalling molecules for skeletal muscle adaptation. Exp Physiol 95:1–9

  • Rajkumar SV, Richardson PG, Hideshima T, Anderson KC (2005) Proteasome inhibition as a novel therapeutic target in human cancer. J Clin Oncol 23:630–639

    Article  CAS  PubMed  Google Scholar 

  • Ramsay ID (1966) Muscle dysfunction in hyperthyroidism. Lancet 29:931–934

    Article  Google Scholar 

  • Repetto M, Reides C, Gomez Carretero ML, Costa M, Griemberg G, Llesuy S (1996) Oxidative stress in blood of HIV infected patients. Clin Chim Acta 255:107–117

    Article  CAS  PubMed  Google Scholar 

  • Reznick AZ, Packer L (1994) Oxidative damage to proteins: Spectrophotometric method for carbonyl assay. Methods Enzymol 233:357–363

    Article  CAS  PubMed  Google Scholar 

  • Riis AL, Gravholt CH, Djurhuus CB, Nørrelund H, Jørgensen JO, Weeke J, Møller N (2002) Elevated regional lipolysis in hyperthyroidism. J Clin Endocrinol Metab 87:4747–4753

    Article  CAS  PubMed  Google Scholar 

  • Riis AL, Jørgensen JO, Ivarsen P, Frystyk J, Weeke J, Møller N (2008) Increased protein turnover and proteolysis is an early and primary feature of short-term experimental hyperthyroidism in healthy women. J Clin Endocrinol Metab 93:3999–4005

    Article  CAS  PubMed  Google Scholar 

  • Servais S, Letexier D, Favier R, Duchamp C, Desplanches D (2007) Prevention of unloading-induced atrophy by vitamin E supplementation: links between oxidative stress and soleus muscle proteolysis? Free Radic Biol Med 42:627–635

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Seymen HO, Civelek S, Seven A, Yigit G, Hatemi H, Burcak G (2004) Iron supplementation in experimental hyperthyroidism: effects on oxidative stress in skeletal muscle tissue. Yonsei Med J 45:413–418

    CAS  PubMed  Google Scholar 

  • Smuder AJ, Kavazis AN, Hudson MB, Nelson WB, Powers SK (2010) Oxidation enhances myofibrillar protein degradation via calpain andcaspase-3. Free Radic Biol Med 49:1152–1160

  • Tawa NE Jr, Odessey R, Goldberg AL (1997) Inhibitors of the proteasome reduces the accelerated proteolysis in atrophying rat skeletal muscles. J Clin Invest 100:197–203

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tietze F (1969) Enzymatic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem 27:502–522

    Article  CAS  PubMed  Google Scholar 

  • Tonon J, Cecchini AL, Brunnquell CR, Bernardes SS, Cecchini R, Guarnier FA (2013) Lung injury-dependent oxidative status and chymotrypsin-like activity of skeletal muscles in hamsters with experimental emphysema. BMC Musculoskelet Disord 14:39

    Article  PubMed Central  PubMed  Google Scholar 

  • Venditti P, Di Meo S (2006) Thyroid hormone-induced oxidative stress. Cell Mol Life Sci 63:414–434

    Article  CAS  PubMed  Google Scholar 

  • Venditti P, Di Stefano L, Di Meo S (2009) Vitamin E reduces cold-induced oxidative stress in rat skeletal muscle decreasing mitochondrial H2O2 release and tissue susceptibility to oxidants. Redox Rep 14:167–175

    Article  CAS  PubMed  Google Scholar 

  • Venditti P, Di Stefano L, Di Meo S (2013) Vitamin E management of oxidative damage-linked dysfunctions of hyperthyroid tissues. Cell Mol Life Sci 70:3125–3144

    Article  CAS  PubMed  Google Scholar 

  • Videla LA, Fernández V, Tapia G, Varela P (2007) Thyroid hormone calorigenesis and mitochondrial redox signaling: upregulation of gene expression. Front Biosci 12:1220–1228

    Article  CAS  PubMed  Google Scholar 

  • Wharton DC, Tzagoloff A (1967) Cytochrome oxidase from beef heart mitochondria. Methods Enzymol 10:5127–5128

    Google Scholar 

  • Yamada T, Mishima T, Sakamoto M, Sugiyama M, Matsunaga S, Wada M (2006) Oxidation of myosin heavy chain and reduction in force production in hyperthyroid rat soleus. J Appl Physiol 100:1520–1526

    Article  CAS  PubMed  Google Scholar 

  • Zingg JM, Azzi A (2004) Non-antioxidant activities of vitamin E. Curr Med Chem 11:1113–1133

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alessandra Lourenço Cecchini.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bernardes, S.S., Guarnier, F.A., Marinello, P.C. et al. Reactive oxygen species play a role in muscle wasting during thyrotoxicosis. Cell Tissue Res 357, 803–814 (2014). https://doi.org/10.1007/s00441-014-1881-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-014-1881-1

Keywords

Navigation