Effects of Selected Inhibitors of Protein Kinases and Phosphatases on Cellular Respiration: An In Vitro Study

Autor: Saeeda Almarzooqi, Robert Mallon, Hidaya Mohammed Abdul-Kader, Sami Shaban, Alia Albawardi, Abdul-Kader Souid, Ali S Alfazari, Dhanya Saraswathiamma
Rok vydání: 2014
Předmět:
Zdroj: Journal of Clinical Toxicology.
ISSN: 2161-0495
DOI: 10.4172/2161-0495.1000212
Popis: Inhibitors of protein kinases/phosphatases are known to alter cellular metabolism. Effects of these rapidly identified small molecules on cellular respiration (mitochondrial O2 consumption) have not been adequately investigated, especially in healthy organs. This in vitro study measured cellular respiration in tissues from C57BL/6 mice with and without GSK2126458 (PI3K/mTOR inhibitor), BEZ235 (PI3K/mTOR inhibitor), GDC0980 (PI3K/mTOR inhibitor), GSK1120212 (trametinib, MEK inhibitor), sorafenib, regorafenib (multikinase inhibitors), and cyclosporine (calcineurin inhibitor). Cellular respiration was measured by the phosphorescence oxygen analyzer, aided by the O2 probe Pd(II)-meso-tetra-(4-sulfonatophenyl)-tetrabenzoporphyrin. Cyanide inhibited O2 consumption, confirming the oxidation occurred in the respiratory chain. Renal cellular respiration decreased 26-34% in the presence of 10 μM GSK2126458 (p
Databáze: OpenAIRE