Branched chain amino acid aminotransferase-1 regulates tubular epithelial cell injury via P53 signaling.

AIM Explore the effects and molecular mechanism of branched chain amino acid aminotransferase-1 (BCAT1) in regulating renal tubular epithelial cell (TEC) injury.

METHODS Cortices from mice with C57BL/6J were used to isolate TEC.BCAT1 was overexpressed or knocked down in TEC, which was performed by adenovirus vectors. Hydrogen dioxide (H₂O₂) stimulation induced TEC apoptosis. TEC viability was assessed by cell counting kit-8 (CCK-8). TEC apoptosis was evaluated by Cleaved-caspase3 expression and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining. The molecular mechanism of BCAT1 regulating TEC injury by P53 signaling was investigated by using PFT-1α, a P53 inhibitor.

RESULTS In H₂O₂-induced apoptotic TEC, a declined expression of BCAT1 mRNA and protein was observed (P<0.01). BCAT1 knockdown exacerbated H₂O₂-induced TEC apoptosis (P<0.01), whereas overexpressing BCAT1 ameliorated it (P<0.01). Expression of P53 downstream target genes further elevated when silencing BCAT1 in H₂O₂-induced TEC, suggesting the activation of P53 signaling (P<0.05). PFT-1α reversed detrimental effects of silencing BCAT1 in H₂O₂-induced TEC apoptosis (P<0.01).

CONCLUSION BCAT1 regulates TEC injury through P53 signaling and might serve as a therapeutic target for chronic kidney disease.