Characterization of aldehyde dehydrogenase isoenzymes in Man, Macaque and Dog skeletal muscles
Résumé
Aldehyde dehydrogenases (ALDH) participate to the metabolism and detoxification of aldehydes and play important roles in cell survival. Moreover, the coordinated expression of several isoenzymes (e.g. ALDH-1A1, -1A2, -1A3, -1B1, -8A1) is finely tuned to regulate the production of retinoic acid involved in the formation of several tissues. However, the localization of ALDHs-expressing cells within muscle tissues, their evolution during ageing or in pathological contexts, their potential functions, are scarcely described. In skeletal muscle, we previously described a population of ALDH+ /CD34- cells harboring myogenic capacities amenable to use in cell therapy. Here, we explored the presence and persistence of these cells in tissues of human donors (healthy, young or aged, versus patients presenting Duchenne muscular dystrophy), of non-human primates (healthy, several anatomical territories being compared), and of dogs (healthy versus the Golden Retriever model of Duchenne muscular Dystrophy). While no significant variation was observed with ageing or between anatomical territories, important changes were manifested between healthy and pathological tissues. We identified extracellular markers associated with expression of ALDH activity. Phenotypic characterization indicated that human ALDH+ /CD34- cells are mainly associated with the extracellular markers CD9, CD36, CD49a, CD49c, CD49f, CD106, CD146, CD184, some being associated to myogenic capacities. We identified several isoenzymes expressed by myogenic and non-myogenic cells present in muscle ex vivo and in vitro at the protein and mRNA levels. Histological analysis ex vivo documented the presence of different cell types harboring isoenzymes in specific anatomical locations, i.e. inside muscle fibers, or in satellite-like position, or in the endomysium, or participating to vessel or neural architectures. Cytological analysis identified cell populations expressing different isoenzymes in vitro (ALDH-1A1, -1A2, -1A3, -2, -3A1, -3A2, -3B1, - 3B2, -4A1, -7A1, -8A1). Finally the analysis of gene expression suggested that, at least, ALDH-1A1, -1A3, -1B1, -2, -3A2, -7A1, -8A1 and -9A1 isoenzymes are involved in muscle homeostasis. This study therefore unveils the importance of the ALDH isoenzymes family in skeletal muscle physiology