Metabolic profile of skeletal muscle satellite cells: role of aldehydes and aldehyde dehydrogenase 2.

Author(s)

Katia Maria Gomes Andrade

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2020-04-30

Examining board members

Julio Cesar Batista Ferreira; Guilherme Giannini Artioli; Fabiana de Sant'Anna Evangelista; Anselmo Sigari Moriscot

• Advisor: Julio Cesar Batista Ferreira

Abstract

Skeletal muscle stem cells, termed satellite cells, play an important role in the regeneration of skeletal muscle. Oxidative metabolism directly affects both activation and division of satellite cells. Another process that modulates the fate of satellite cells is the increase of reactive oxygen species. Recently, we reported that oxidative stress lead to accumulation of toxic aldehydes, which have a negative impact in cardiac cells by making adducts with proteins and DNA. It is important to highlight that the role of aldehydes in the activation and maintenance of satellite cells is still unknown. The main enzyme responsible for the removal of toxics aldehydes, such as 4-hydroxy-2-nonenal (4-HNE), is the mitochondrial aldehyde dehydrogenase 2 (ALDH2). Impaired ALDH2 activity contributes to the progression of chronic diseases such as heart failure and peripheral arterial disease. Here, we aim to characterize the metabolic profile of satellite cell/myoblasts/myotubes from WT and ALDH2 knock-in mice, as well as their susceptibility to aldehyde overload associated with skeletal muscle degeneration. Our hypothesis is that aldehydic load disrupts satellite cell metabolism and fate. Our results indicate that acute 4-HNE treatment of proliferating C2C12 myoblasts reduces mitochondrial metabolism, cell proliferation rate, and alters cell cycle. Of interest, ALDH2 knock-in mice, which display reduced ability to metabolize aldehydes, have decreased skeletal muscle pool of satellite cells with impaired proliferative capacity. Moreover, primary myoblasts in culture from ALDH2 knock-in mice present reduced mitochondrial content and bioenergetics compared with WT. This ALDH2 knock-in phenotype is followed by a premature differentiation of myoblasts into myotubes upon serum starvation compared with WT. Our results together suggest that both aldehyde excess and reduced ALDH2 activity and expression negatively affect satellite cell biology. (AU)

• FAPESP's process: 14/15187-1 - Characterization of skeletal muscle satellite cells metabolism and redox balance: role of aldehydes as metabolic sensors
• Grantee: Kátia Maria Gomes Andrade
• Support Opportunities: Scholarships in Brazil - Doctorate