Correlation Engine 2.0
Clear Search sequence regions


Sizes of these terms reflect their relevance to your search.

Protein synthesis inhibitors are commonly used for measuring protein degradation rates, but may cause cytotoxicity via direct or indirect mechanisms. This study aimed to identify concentrations providing optimal inhibition in the absence of overt cytotoxicity. Actinomycin D, cycloheximide, emetine, and puromycin were assessed individually, and in two-, three-, and four-drug combinations for protein synthesis inhibition (IC50 ) and cytotoxicity (CC50 ) over 72 h. Experiments were conducted in HepG2 cells and primary rat hepatocytes (PRH). IC50 for actinomycin D, cycloheximide, emetine, and puromycin were 39 ± 7.4, 6600 ± 2500, 2200 ± 1400, and 1600 ± 1200 nmol/L; with corresponding CC50 values of 6.2 ± 7.3, 570 ± 510, 81 ± 9, and 1300 ± 64 nmol/L, respectively, in HepG2 cells. The IC50 were 1.7 ± 1.8, 290 ± 90, 620 ± 920, and 2000 ± 2000 nmol/L, with corresponding CC50 values of 0.98 ± 1.8, 680 ± 1300, 180 ± 700, and 1600 ± 1000 (SD) nmol/L, respectively, in PRH. CC50 were also lower than the IC50 for all drug combinations in HepG2 cells. These data indicate that using pharmacological interference is inappropriate for measuring protein degradation over a protracted period, because inhibitory effects cannot be extricated from cytotoxicity. © 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

Citation

Christina Chan, Philip Martin, Neill J Liptrott, Marco Siccardi, Lisa Almond, Andrew Owen. Incompatibility of chemical protein synthesis inhibitors with accurate measurement of extended protein degradation rates. Pharmacology research & perspectives. 2017 Oct;5(5)

Expand section icon Mesh Tags

Expand section icon Substances


PMID: 28971619

View Full Text