Dietary regulation and localization of apoptosis cascade proteins in the colonic crypt

This study was designed primarily to assess the localization of apoptosis c ascade proteins along the rat colonic crypt and secondarily to test whether the activity and/or localization of these proteins are affected by the enr ichment of the diet with the soluble fiber pectin. Expression of apoptosis cascade proteins was assessed in isolated colonocytes harvested from the lu minal and basal crypt colonocyte populations. Two different dietary regimen s were tested: a standard diet (diet A), and a diet enriched in pectin (die t B), a soluble fiber that undergoes fermentation in the cecum and produces high concentrations of intracolonic short-chain fatty acids. Caspase-1 exp ression was maximal in luminal colonocytes of rats fed diet B, as evidenced by Western blot and immunohistological analyses. Expression of the cleaved poly(ADP-ribose) polymerase product was elevated in both the luminal and b asal colonocytes of the pectin-fed group, whereas in rats fed diet A, the e xpression was lower, especially in basal crypt colonocytes. The highest exp ression of the antiapoptotic protein Bcl-2 was observed in the lower compar tments of the colonic crypt tissue and was maximal in the rat group fed a s tandard diet. The apoptotic index in colonocytes of rats fed diet B was hig her than that measured in rats fed diet A. Cumulatively, our results indica te that apoptosis cascade proteins are differentially localized along the l umen-crypt axis, and their expression and activity may be controlled by die tary components. These results may, at least partially, account for the doc umented protective effect of butyrogenic fibers on colorectal cancer. J. Ce ll. Biochem. 77:18-29, 2000. (C) 2000 Wiley-Liss,Inc.