Anthracycline anticancer drugs, such as doxorubicin (DOX), can induce cardiotoxicity supposed to be related to mitochondrial damage. We have recently demonstrated that a branchedchain amino acid (BCAA)-enriched mixture (BCAAem), supplemented with drinking water to middle-aged mice, was able to promote mitochondrial biogenesis in cardiac and skeletal muscle. To maximally favor and increase oxidative metabolism and mitochondrial function, here we tested a new original formula, composed of essential amino acids, tricarboxylic acid cycle precursors and co-factors (named 5), in HL-1 cardiomyocytes and mice treated with DOX. We measured mitochondrial biogenesis, oxidative stress, and BCAA catabolic pathway. Moreover, the molecular relevance of endothelial nitric oxide synthase (eNOS) and mechanistic/mammalian target of rapamycin complex 1 (mTORC1) was studied in both cardiac tissue and HL-1 cardiomyocytes. Finally, the role of Krüppel-like factor 15 (KLF15), a critical transcriptional regulator of BCAA oxidation and eNOS-mTORC1 signal, was investigated. Our results demonstrate that the 5 mixture prevents the DOX-dependent mitochondrial damage and oxidative stress better than the previous BCAAem, implying a KLF15/eNOS/mTORC1 signaling axis. These results could be relevant for the prevention of cardiotoxicity in the DOX-treated patients.
A Special Amino-Acid Formula Tailored to Boosting Cell Respiration Prevents Mitochondrial Dysfunction and Oxidative Stress Caused by Doxorubicin in Mouse Cardiomyocytes / L. Tedesco, F. Rossi, M. Ragni, C. Ruocco, D. Brunetti, M.O. Carruba, Y. Torrente, A. Valerio, E. Nisoli. - In: NUTRIENTS. - ISSN 2072-6643. - 12:2(2020 Jan), pp. 282.1-282.20.
|Titolo:||A Special Amino-Acid Formula Tailored to Boosting Cell Respiration Prevents Mitochondrial Dysfunction and Oxidative Stress Caused by Doxorubicin in Mouse Cardiomyocytes|
VALERIO, ALESSANDRA (Corresponding)
NISOLI, ENZO (Corresponding)
|Parole Chiave:||Krüppel-like factor 15; branched-chain amino acids; cardiomyocytes; doxorubicin; endothelial nitric oxide synthase; mechanistic/mammalian target of rapamycin; mitochondria; oxidative stress; peroxisome proliferator-activated receptor coactivator 1; tricarboxylic acid cycle|
|Settore Scientifico Disciplinare:||Settore MED/26 - Neurologia|
|Data di pubblicazione:||gen-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3390/nu12020282|
|Appare nelle tipologie:||01 - Articolo su periodico|