Studies on the mechanism of butyrate-induced morphological changes in KB cells

KB cells treated with propionate, butyrate and valerate change drastically in their morphology, displaying long processes and few surface microvilli in scanning electron micrographs. Butyrate was the most effective compound and its effects were blocked by actinomycin D, cycloheximide and colchicine, but not by flurbiprofen or thymidine. Butyrate treatment resulted in a 14-fold increase in the specific activity of CMP-sialic acid: lactosylceramide sialosyltransferase when added to cells grown in medium at pH 7.0; lower induction (10-fold) of this enzyme occurred when the medium was above or below pH 7 (6.5-7.5). The subcellular fraction with the highest specific activity sedimented at 100 000 g. The product (II³-α-N-acetylneuraminosyl-lactosylceramide, GM₃) of this glycosyltransferase, when added in pure form or in a liposomal complex, was unable to cause morphological changes in KB cells. Surface labelling (galactose oxidase-[³H]sodium borohydride) of KB cells grown with or without butyrate displayed a pronounced incorporation of tritium into globotriglycosylceramide (GL3) with twice control levels in the butyrate-treated cells. The total incorporation of tritium into glycoproteins was unchanged by butyrate treatment. KB cells show a pronounced increase in DNA synthesis 10-11 h after release from butyrate treatment. A broad but symmetrical curve of DNA synthesis versus time indicates that butyrate treatment blocks the KB cells since a synchronous population results when the cells are released from butyrate.