Effect of protease inhibitors on in vitro breakdown of uterine histones from hormone-treated rats.
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Biomedical subjects
Publications and source records attributed to W Troll.
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Previous work has suggested that intracellular proteolysis may play a role in lymphocyte stimulation. An inhibitor of proteolysis, epsilon amino caproic acid (EACA) was studied for its effect on the lymphocyte response to phytohemagglutinin (PHA). EACA was found to inhibit several parameters of lymphocyte stimulation (e.g. DNA, RNA, and protein synthesis as well as alterations in morphology) This inhibition was not due to diminished cellular viability and did not permanently impair the capacity of the lymphocyte to subsequently respond to PHA. Additionally, there was no evidence that this inhibition was due to other possible effects of EACA, such as alterations in Na(+) - K(+) transport, competitive amino acid deprivation or interference with PHA binding. Moreover, the inhibitors of proteolysis, tosyl arginine methyl ester (TAME), tosyl lysine chloromethyl ketone (TLCK), and tosyl phenyl-alanine chloromethyl ketone (TPCK), were also shown to inhibit lymphocyte stimulation.EACA was most effective when added during the first 24 hr of stimulation. Therefore, these experiments support the hypothesis that proteolysis is an essential step in the early phase of lymphocyte activation.
Three synthetic inhibitors of proteases (tosyl lysine chloromethyl ketone, tosyl phenylalanine chloromethyl ketone, and tosyl arginine methyl ester) inhibit the tumorigenesis initiated in mouse skin by 7,12-dimethylbenz(a)anthracene and promoted by croton oil or its active principle, phorbol ester. These protease inhibitors, when applied directly to mouse skin, inhibit some of the irritant effects of the tumor promoter and are not toxic.
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