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Impact of MuRF-1 and MuRF-2 to skeletal muscle wasting under experimental hyperthyroidism

Grant number: 19/06819-8
Support type:Scholarships abroad - Research Internship - Doctorate (Direct)
Effective date (Start): August 01, 2019
Effective date (End): February 28, 2020
Field of knowledge:Biological Sciences - Morphology - Anatomy
Principal Investigator:Anselmo Sigari Moriscot
Grantee:André Cruz de Oliveira
Supervisor abroad: Siegfried Labeit
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: University of Mannheim, Germany  
Associated to the scholarship:17/09398-8 - Interplay betweeen myostatin and mTORC1 pathways in skeletal muscle: implications for a thyroid hormone biological action, BP.DD


Skeletal muscle is a major target of thyroid hormone (T3), this hormone acts mainly through gene transcription modulation and it is known for inducing muscle proteolysis. Previously, we addressed the effects of T3 in the protein synthesis and degradation related pathways by microarray analysis. From these data, we have shown that high levels of T3 stimulate protein breakdown by ubiquitin-proteasome system stimulation whereas we indicated that protein synthesis could be diminished by down-regulation of an mTORC1 subunit called Raptor. Linking catabolism and anabolism are myostatin pathway that could inhibit protein synthesis while induces protein breakdown by MuRF1/2 up-regulation leading the skeletal muscle atrophy. For this reason, our aim in this BEPE proposal is to understand the impact of the ubiquitin-proteasome pathway in the skeletal mass loss induced by T3. For that purpose, we will manipulate MuRF1/2 levels by utilizing MuRF1 and MuRF-2 knockout mice and also knock down myostatin since it is known that myostatin can increase MuRF1 transcription. With this BEPE proposal along with the Doctorate proposal, we intend to gain insight on the relative role of protein synthesis and degradation upon the muscle wasting effects of T3. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
LABEIT, SIEGFRIED; HIRNER, STEPHANIE; BOGOMOLOVAS, JULIJUS; CRUZ, ANDRE; MYRZABEKOVA, MOLDIR; MORISCOT, ANSELMO; BOWEN, THOMAS SCOTT; ADAMS, VOLKER. Regulation of Glucose Metabolism by MuRF1 and Treatment of Myopathy in Diabetic Mice with Small Molecules Targeting MuRF1. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 4 FEB 2021. Web of Science Citations: 0.
ADAMS, VOLKER; GUSSEN, VICTORIA; ZOZULYA, SERGEY; CRUZ, ANDRE; MORISCOT, ANSELMO; LINKE, AXEL; LABEIT, SIEGFRIED. Small-Molecule Chemical Knockdown of MuRF1 in Melanoma Bearing Mice Attenuates Tumor Cachexia Associated Myopathy. CELLS, v. 9, n. 10 OCT 2020. Web of Science Citations: 0.

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