Interaction between monensin and lysosomotropic amines in the regulation of the processing of epidermal growth factor by BALB/c 3T3 cells |
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Authors: | Janet L Cooper Richard Selinfreund Eric Wakshull Walker Wharton |
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Institution: | (1) Experimental Pathology Group, Life Sciences Division, University of California, Los Alamos National Laboratory, 87545 Los Alamos, New Mexico, USA;(2) Los Alamos National Laboratory, LS-4, Mail Stop M888, 87545 Los Alamos, New Mexico, USA |
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Abstract: | Monensin, like the lysosomotropic amines Chloroquine and methylamine, caused a large accumulation of 125I-EGF in BALB/c-3T3 cells that was due to specific increases in the amount of intracellular intact hormone. However using a pulse-chase paradigm of 125I-EGF accumulation, marked differences were observed between monensin and the amines. When EGF was accumulated in the presence of monensin, there was a gradual loss of cell-bound radioactivity during a chase in the absence of the drug, and the labeled material recovered in. the medium primarily consisted of degraded hormone. The continued presence of monensin in the chase medium substantively prevented the loss of cell bound material, and what little was recovered in the medium consisted of intact 125I-EGF. In contrast, when 125I-EGF was accumulated in the presence of methylamine, predominately intact peptide was lost from the cells at a relatively high rate during the chase whether or not methylamine remained in the medium. When monensin was present in the chase medium following accumulation in the presence of either Chloroquine or methylamine, the loss of intracellular 125I-EGF was essentially blocked. |
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Keywords: | Chloroquine methylamine lysosomes pH gradients |
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