Journal article
The AMPK activator ATX-304 alters cellular metabolism to protect against cisplatin-induced acute kidney injury
M Katerelos, K Gleich, G Harley, K Loh, JS Oakhill, BE Kemp, DP de Souza, VK Narayana, MT Coughlan, A Laskowski, NXY Ling, L Murray-Segal, R Brink, M Lee, DA Power, PF Mount
Biomedicine and Pharmacotherapy | ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER | Published : 2024
Open access
Abstract
Acute kidney injury (AKI) disrupts energy metabolism. Targeting metabolism through AMP-activated protein kinase (AMPK) may alleviate AKI. ATX-304, a pan-AMPK activator, was evaluated in C57Bl/6 mice and tubular epithelial cell (TEC) cultures. Mice received ATX-304 (1 mg/g) or control chow for 7 days before cisplatin-induced AKI (CI-AKI). Primary cultures of tubular epithelial cells (TECs) were pre-treated with ATX-304 (20 µM, 4 h) prior to exposure to cisplatin (20 µM, 23 h). ATX-304 increased acetyl-CoA carboxylase phosphorylation, indicating AMPK activation. It protected against CI-AKI measured by serum creatinine (control 0.05 + 0.03 mM vs ATX-304 0.02 + 0.01 mM, P = 0.03), western blot f..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
This study was funded by an Ideas Grant from the National Health and Medical Research Council (Government of Australia) , Grant ID 2010600. ATX-304 was supplied by Amplifier Therapeutics (Cambrian Bio Pharma, Inc., NY, USA) .