14 Induction of Ganglioside Biosynthesis in Cultured Cells by Butyric Acid
Downloaded by AUBURN UNIV on September 12, 2017 | http://pubs.acs.org Publication Date: July 31, 1980 | doi: 10.1021/bk-1980-0128.ch014
PETER H. FISHMAN and RICHARD C. HENNEBERRY National Institute of Neurological and Communicative Disorders and Stroke, The National Institutes of Health, Bethesda, MD 20205
The pleiotropic biochemical changes induced in mammalian cells in culture by butyric acid are many, varied and well documented (1). Although the initial reports on this subject appeared only six years ago, the number of published papers in this area has increased rapidly and is now approaching a hundred. The first reported observations of an effect of this fatty acid on cultured cells involved morphological changes. Ginsburg et al (2) noticed striking alterations in the shape of several lines of cultured cells including HeLa after exposure to butyrate. Independently, Wright (3) reported that butyrate caused morphological changes in Chinese hamster ovary (CHO) cells. Contrary to popular assumption, in neither of these studies was butyrate being used as a control for butyrylated derivatives of cyclic nucleotides. In 1974, our laboratories reported that the activity of CMP-sialic acid:lactosylceramide sialyl transferase and amount of its biosynthetic product ganglioside GM3 (N-acetylneuraminylgalactosylglucosylceramide) increased dramatically in butyrate-treated HeLa cells (4). More recently, we have found that the gangliosideGM1(galactosyl-N-acetyl-galactosaminyl-[N-acetylneuraminyl]galactosylglucosylceramide) is also increased in HeLa cells exposed to butyrate (5). GM1 has been implicated as the cell surface receptor for cholera toxin (6,7). In this article, we will review the effects of butyrate on cell morphology and ganglioside synthesis and provide conclusive evidence thatGM1is the cholera toxin receptor. In addition, we will describe some novel effects of cycloheximide on the turnover of membrane gangliosides. Effects of Butyrate on Cell Morphology In HeLa cells, the striking morphological alterations which follow exposure of the cells to butyrate are characterized by the extension of neurite-like processes (Fig. 1). No significant differences in the fine structure of the cell surface was observed by scanning electron micrography (Fig. 1). In addition to butyrate, propionate and pentanoate but not other homologous 0-8412-0556-6/ 80/ 47-128-223S5.00/ 0 © 1980 American Chemical Society Sweeley; Cell Surface Glycolipids ACS Symposium Series; American Chemical Society: Washington, DC, 1980.
Downloaded by AUBURN UNIV on September 12, 2017 | http://pubs.acs.org Publication Date: July 31, 1980 | doi: 10.1021/bk-1980-0128.ch014
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f a t t y acids a l t e r e d HeLa morphology U , 8 ) . C y c l i c AMP o r i t s but y r y l a t e d d e r i v a t i v e s d i d not induce shape changes i n HeLa (2) although they d i d e f f e c t the morphology o f other c e l l s such as CHO ( 9 J . HeLa c e l l s responded to butyrate i n serum-free medium which by i t s e l f had no e f f e c t on c e l l shape ( 8 ) . In c o n t r a s t , neuroblastoma c e l l s extended long processes when deprived o f serum (10) but a l s o developed these n e u r i t e s when exposed to b u t y r a t e (11). The formation o f the n e u r i t e - l i k e processes appears to be dependent on assembly o f microtubules as c o l c h i c i n e and Colcemid, a n t i m i c r o t u b u l e drugs, prevented shape changes i n the presence o f b u t y r a t e (
