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Effects of 5‐azacytidine, sodium butyrate, and phorbol esters on amino acid transport system A in a kidney epithelial cell line, MDCK: Evidence for multiple mechanisms of regulation
Author(s) -
Boerner Paula,
Saier Milton H.
Publication year - 1988
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041370114
Subject(s) - butyrate , sodium butyrate , cell culture , butyric acid , biochemistry , amino acid , acetylation , biology , chemistry , microbiology and biotechnology , fermentation , gene , genetics
Abstract Neutral amino acid transport by system A was investigated in the epithelial cell lines MDCK and MDCK‐T 1 . The latter line is a chemically induced, oncogenically transformed line derived from MDCK. Inducers of differentiation, sodiuum butyrate and 5‐azacytidine, and a tumor promotor, TPA, were used as probes to delineate pathways of regulation involved in system A response to a variety of physiological conditions and agents. Azacytidine, an inhibitor of DNA methylation, and butyrate, an enhancer of histone acetylation, inhibited expression of system A, had little effect on system ASC, and slightly stimulated system L. Inhibition of system A expression by butyrate and azacytidine occurred under different conditions. Increases in system A activity due to amino acid starvation or transformation were inhibited by butyrate but not by azacytidine. Repressed system A activity, normally observed in the presence of high levels of amino acids, was more sensitive to azacytidine than to butyrate. The tumor promotor, TPA, stimulated system A activity in MDCK cells under normal growth conditions but did not stimulate activity in amino acid‐starved MDCK cells or in MDCK‐T 1 cells. Stimulation of system A activity by TPA was prevented by prior exposure to butyrate but not to azacytidine. These results suggest (1) that system A expression observed in growing amino‐acid‐repressed MDCK cells is modulated by an azacytidine‐sensitive mechanism and (2) that the elevated expression of system A activity induced by amino acid starvation, by chemical transformation to MDCK‐T 1 , and by TPA is modulated by a butyrate‐sensitive mechanism.