Abstract:
AIM To determine the regulatory role of branched chain amino acid aminotransferase-1 (BCAT1) in the survival of adipose-derived mesenchymal stem cells (ADSCs).
METHODS ADSCs were isolated from white adipose tissues of male Sprague Dawley rats. BCAT1 expression was knocked down or over-expressed in ADSCs by adenovirus transfection and ADSC apoptosis was induced by hydrogen dioxide stimulation. ADSC apoptosis was evaluated by CCK-8 cell viability assay, cleaved caspase-3 expression, and TUNEL staining. The activity of P53 was suppressed by the specific inhibitor PFT-1α in control or BCAT1 silencing ADSCs.
RESULTS BCAT1, rather than BCAT2, was the predominant subtype expressed in ADSCs. Silencing of BCAT1 exacerbated, whereas BCAT1 over-expression ameliorated hydrogen dioxide-induced ADSC apoptosis. The downstream targets of P53 were significantly increased in BCAT1 knock-downed ADSCs when stimulated by hydrogen dioxide. Inhibition of P53 by its specific inhibitor PFT-1α reversed the adverse impact of BCAT1 silencing on ADSC survival.
CONCLUSION BCAT1 regulates ADSC survival via a P53-dependent manner, revealing that BCAT1 is a promising target to enhance ADSC survival and their cardioprotective efficacy.