Decreased PGC1-α levels and increased apoptotic protein signaling are associated with the maladaptive cardiac hypertrophy in hyperthyroidism
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Hyperthyroidism can lead to the activation of proteins which are associated with inflammation, apoptosis, hypertrophy, and heart failure. This study aimed to explore the inflammatory and apoptotic proteins involved in the hyperthyroidism-induced cardiac hypertrophy establishment. Male Wistar rats were divided into control and hyperthyroid (12 mg/L L-thyroxine, in drinking water for 28 days) groups. The expression of inflammatory and apoptotic signaling proteins was quantified in the left ventricle by Western blot. Hyperthyroidism was confirmed by evaluation of T3 and T4 levels, as well as cardiac hypertrophy development. There was no change in the expression of HSP70, HIF1-α, TNF-α, MyD88, p-NFκB, NFκB, p-p38, and p38. Reduced expression of p53 and PGC1-α was associated with increased TLR4 and decreased IL-10 expression. Decreased Bcl-2 expression and increased Bax/Bcl-2 ratio were also observed. The results suggest that reduced PGC1-α and IL-10, and elevated TLR4 proteins expression could be involved with the diminished mitochondrial biogenesis and anti-inflammatory response, as well as cell death signaling, in the establishment of hyperthyroidism-induced maladaptive cardiac hypertrophy.
KeywordsCardiac hypertrophy cell death hyperthyroidism inflammation PGC1-α
Veterinary medical support from Dr. André Ricardo Ribeiro Belló is acknowledged. We also acknowledge Professor Ilma Simoni Brum, Physiology Department, UFRGS, for providing the p53 antibody. This paper was written during a scholarship provided by the International Cooperation Program CAPES/DFATD at the University of Manitoba. This study was funded by Conselho Nacional de Desenvolvimento Científico e tecnológico, Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
- Araujo ASR, Diniz GP, Seibel FER, Branchini G, Ribeiro MFM, Brum IS, Khaper N, Barreto-Chaves ML and Belló-Klein A 2011 Reactive oxygen and nitrogen species balance in the determination of thyroid hormones-induced cardiac hypertrophy mediated by renin–angiotensin system. Mol. Cell. Endocrinol. 333 78–84CrossRefGoogle Scholar
- Dijsselbloem N, Goriely S, Albarani V, Gerlo S, Francoz S, Marine J-C, Goldman M, Haegeman G and Vanden Berghe W 2007 A critical role for p53 in the control of NF-kappaB-dependent gene expression in TLR4-stimulated dendritic cells exposed to Genistein. J. Immunol. 178 5048–5057CrossRefGoogle Scholar
- Ferreira A and Ávila S 2013 Diagnóstico Laboratorial das Principais Doenças Infecciosas e Auto-imunes. 2nd ed. (Rio de Janeiro: Guanabara Koogan).Google Scholar
- Madenspacher JH, Azzam KM, Gowdy KM, Malcolm KC, Nick JA, Dixon D, Aloor JJ, Draper DW, Guardiola JJ, Shatz M, Menendez D, Lowe J, Lu J, Bushel P, Li L, Merrick BA, Resnick MA and Fessler MB 2013 p53 integrates host defense and cell fate during bacterial pneumonia. J. Exp. Med. 210 891–904CrossRefGoogle Scholar
- Narula J, Pandey P, Arbustini E, Haider N, Narula N, Kolodgie FD, Bello Bd, Semigran MJ, Bielsa-Masdeu A, Dec Gw, Israels S, Ballester M, Virmanii R, Saxena S and Kharbanda S 1999 Apoptosis in heart failure: release of cytochrome c from mitochondria and activation of caspase-3 in human cardiomyopathy. Proc. Natl. Acad. Sci. U S A 96 8144–8149CrossRefGoogle Scholar
- Satoh M, Shimoda Y, Akatsu T, Ishikawa Y, Minami Y and Nakamura M 2006 Elevated circulating levels of heat shock protein 70 are related to systemic inflammatory reaction through monocyte Toll signal in patients with heart failure after acute myocardial infarction. Eur. J. Heart Fail. 8 810–815CrossRefGoogle Scholar
- Summermatter S, Baum O, Santos G, Hoppeler H and Handschin C 2010 Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) promotes skeletal muscle lipid refueling in vivo by activating de novo lipogenesis and the pentose phosphate pathway. J Biol. Chem. 285 32793–32800CrossRefGoogle Scholar
- Timmers L, Sluijter JPG, van Keulen JK, Hoefer IE, Nederhoff MGJ, Goumans M-J, Doevendans PA, van Echteld CJ, Joles JA, Quax PH, Piek JJ, Pasterkamp G and de Kleijn DP 2008 Toll-Like receptor 4 mediates maladaptive left ventricular remodeling and impairs cardiac function after myocardial infarction. Circ. Res. 102 257–264CrossRefGoogle Scholar
- Yang Y, Lv J, Jiang S, Ma Z, Wang D, Hu W, Deng C, Fan C, Di S, Sun Y and Yi W 2016 The emerging role of Toll-like receptor 4 in myocardial inflammation. Cell Death. Dis. 7 e2234–e2234Google Scholar