Bcl-w is an important determinant of damage-induced apoptosis in epithelia of small and large intestine.
The potential role of the bcl-2 relative bcl-w as a physiological regulator of apoptosis in intestinal epithelia has been investigated. Immunoblots for bcl-w with new monoclonal antibodies revealed that it was expressed in the small intestine and colon, among other murine tissues, as well as in six human tumour cell lines of epithelial origin, including two colon carcinoma lines. To assess whether bcl-w regulates either spontaneous or damage-induced apoptosis in the small intestine or colon, apoptosis in intestinal crypts of bcl-w -/- and wild-type mice was quantified microscopically on a cell positional basis. Spontaneous apoptosis within crypt epithelia was not significantly increased by loss of bcl-w, in either the small intestine or midcolon. However, after treatment with the cytotoxic drug 5-fluorouracil or with gamma-radiation, the bcl-w-null animals exhibited substantially more apoptosis than their wild-type counterparts in both tissues. The greatest enhancement of apoptosis attributable to the absence of bcl-w (up to sixfold) occurred in the small intestine. Hence, bcl-w is an important determinant of damage-induced apoptosis in intestinal epithelia, and unlike bcl-2, which regulates only colonic apoptosis, plays a major role in small intestinal epithelium.
Pritchard
D M
DM
CRC Department of Epithelial Biology, Paterson Institute, Christie Hospital NHS Trust, Manchester, UK.
Print
C
C
O'Reilly
L
L
Adams
J M
JM
Potten
C S
CS
Hickman
J A
JA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D051017:Apoptosis Regulatory Proteins; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D005472:Fluorouracil / Q000494:pharmacology; D005720:Gamma Rays; D006801:Humans; D007420:Intestine, Large / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011506:Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D051017:Apoptosis Regulatory Proteins; C491073:BCL2L2 protein, human; C101155:Bcl2l2 protein, mouse; D011506:Proteins; D005472:Fluorouracil