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

• Grant number: 19/06819-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: August 01, 2019
• End date: February 28, 2020
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Anselmo Sigari Moriscot
• Grantee: André Cruz de Oliveira
• Supervisor: Siegfried Labeit
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: 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

Abstract

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)

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. (19/06819-8, 15/04090-0)

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. (15/04090-0, 19/06819-8)