| Popis: |
Background Satellite cells (SC) constitute the stem cell population of skeletal muscle tissue and are determinants for myogenesis. Aldehyde Dehydrogenase 1 (ALDH1) enzymatic activity correlates with myogenic properties of SCs and, recently, we could show co-localization of its isoforms ALDH1A1 and ALDH1A3 in SCs of human skeletal muscle. ALDH1 is not only the pacemaker enzyme in retinoic acid signaling and differentiation, but also protecting cell maintenance against oxidative stress products. However, the molecular mechanism of ALDH1 in SC activation and regulation of myogenesis has not yet been characterized. In regard of ALDH1A1 and ALDH1A1 expression in myogenesis human RH30 and murine C2C12 myoblast cell lines were investigated using Western Blot, Immunofluorescence and Aldefluor Assay. Results Here, we show, that isoforms ALDH1A1 and ALDH1A3 are pivotal factors in the process of myogenic differentiation, since ALDH1A1 knock-out and ALDH1A3 knock-out, respectively, impaired differentiation potential. Recombinant re-expression of ALDH1A1 and ALDH1A3, respectively, in corresponding ALDH1-isoform knock-out cells recovered their differentiation potential. Most interestingly, the chemical inhibition of enzymatic activity by disulfiram leads to ALDH1A1 and ALDH1A3 protein upregulation and subsequent myogenic differentiation. Conclusion Our findings indicate that ALDH1A1 and ALDH1A3 proteins are important for myogenic differentiation and, therefore, seem to be essential activators and regulators of SCs. |
