Expression proteomics of acute promyelocytic leukaemia cells treated with methotrexate

Biochimica Et Biophysica Acta
Nitin Kumar AgarwalHassan Dihazi

Abstract

Methotrexate was first introduced as a cytotoxic agent that inhibits nucleotide biosynthesis in various cancer disorders; its molecular mechanism remains elusive. To understand the molecular mechanism by which methotrexate induces apoptosis, we analyzed the resulting intracellular protein changes in methotrexate-treated acute promyelocytic leukaemia (HL-60) cells by cysteine-labeled differential in-gel electrophoresis (CL-DIGE) combined with mass spectrometry. Initial CL-DIGE analysis revealed that 24 proteins were differentially expressed (p<0.05) in the HL-60 cell proteome after treatment with 2.5microM methotrexate for 72h. We found that three structural alpha4, alpha5, alpha7 proteasome subunits, a non-catalytic beta3 and two 26S regulatory proteasome subunits were down-regulated in methotrexate-treated HL-60 cells. Western blot analyses further showed that the inhibition of proteasome subunits is accompanied by suppression of NF-kappaB subunits and promotes the accumulation of ubiquitinated proteins. Furthermore, methotrexate activated unfolded protein response by inducing the expression of endoplasmic reticulum-resident proteins such as calreticulin, protein disulphide isomerase A3 and A4, and 78kDa glucose regulated prot...Continue Reading

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Citations

Jul 1, 2010·Genome Medicine·Sigrun M HjelleBjørn T Gjertsen
Jun 24, 2014·Journal of Materials Science. Materials in Medicine·Rahul Misra, Sanat Mohanty
Mar 10, 2012·Free Radical Biology & Medicine·Francisco R M LaurindoDenise de Castro Fernandes
Aug 9, 2011·Expert Review of Proteomics·Marie-Pierre Bousquet-DubouchOdile Burlet-Schiltz
Apr 12, 2013·Expert Review of Proteomics·Ellen Niederberger, Gerd Geisslinger

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