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Ursodeoxycholic acid increases the activities of alkaline sphingomyelinase and caspase-3 in the rat colon.

Cheng, Yajun LU ; Tauschel, Horst-Dietmar ; Nilsson, Åke LU and Duan, Rui-Dong LU (1999) In Scandinavian Journal of Gastroenterology 34(9). p.915-920
Abstract
BACKGROUND:
Ursodeoxycholic acid (UDCA) has been found to inhibit the development of colon carcinoma induced by chemical carcinogens with unidentified mechanisms. Sphingomyelin metabolism has emerged as a novel signal transduction pathway closely related to cell proliferation and apoptosis. We recently found that alkaline sphingomyelinase (SMase) activity was decreased in human colon cancer. The present study is to investigate whether UDCA has effect on the levels of SMase and whether the activity of caspase-3, a key regulatory protease in apoptosis that can be activated by sphingomyelin breakdown products, is also influenced by UDCA.

METHODS:
Rats were fed UDCA in amounts ranging from 37.5 to 300 mg/kg/day for 10 days by... (More)
BACKGROUND:
Ursodeoxycholic acid (UDCA) has been found to inhibit the development of colon carcinoma induced by chemical carcinogens with unidentified mechanisms. Sphingomyelin metabolism has emerged as a novel signal transduction pathway closely related to cell proliferation and apoptosis. We recently found that alkaline sphingomyelinase (SMase) activity was decreased in human colon cancer. The present study is to investigate whether UDCA has effect on the levels of SMase and whether the activity of caspase-3, a key regulatory protease in apoptosis that can be activated by sphingomyelin breakdown products, is also influenced by UDCA.

METHODS:
Rats were fed UDCA in amounts ranging from 37.5 to 300 mg/kg/day for 10 days by gavage. The colonic mucosa was scraped, homogenized, and sonicated. The activities of acid, neutral and alkaline SMases, and caspase-3 were determined.

RESULTS:
UDCA dose-dependently increased alkaline SMase activity in colonic mucosa and faeces, slightly increased acid SMase activity in the mucosa, and had no effect on neutral SMase. UDCA also dose-dependently increased caspase-3 activity in the colonic mucosa, and the increase correlated significantly with the changes in alkaline but not that in acid or neutral SMase activity.

CONCLUSIONS:
UDCA increases alkaline sphingomyelinase and caspase-3 activities, which might be a mechanism involved in its anticarcinogenic effect on colon cancer development. (Less)
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author
; ; and
publishing date
type
Contribution to journal
publication status
published
subject
in
Scandinavian Journal of Gastroenterology
volume
34
issue
9
pages
915 - 920
publisher
Taylor & Francis
external identifiers
  • scopus:0032885918
  • pmid:10522612
ISSN
0036-5521
DOI
10.1080/003655299750025408
language
English
LU publication?
no
id
27cb9078-42b7-4371-938b-975a62bb3a53
date added to LUP
2019-02-03 16:40:58
date last changed
2022-01-31 17:21:55
@article{27cb9078-42b7-4371-938b-975a62bb3a53,
  abstract     = {{BACKGROUND:<br/>Ursodeoxycholic acid (UDCA) has been found to inhibit the development of colon carcinoma induced by chemical carcinogens with unidentified mechanisms. Sphingomyelin metabolism has emerged as a novel signal transduction pathway closely related to cell proliferation and apoptosis. We recently found that alkaline sphingomyelinase (SMase) activity was decreased in human colon cancer. The present study is to investigate whether UDCA has effect on the levels of SMase and whether the activity of caspase-3, a key regulatory protease in apoptosis that can be activated by sphingomyelin breakdown products, is also influenced by UDCA.<br/><br/>METHODS:<br/>Rats were fed UDCA in amounts ranging from 37.5 to 300 mg/kg/day for 10 days by gavage. The colonic mucosa was scraped, homogenized, and sonicated. The activities of acid, neutral and alkaline SMases, and caspase-3 were determined.<br/><br/>RESULTS:<br/>UDCA dose-dependently increased alkaline SMase activity in colonic mucosa and faeces, slightly increased acid SMase activity in the mucosa, and had no effect on neutral SMase. UDCA also dose-dependently increased caspase-3 activity in the colonic mucosa, and the increase correlated significantly with the changes in alkaline but not that in acid or neutral SMase activity.<br/><br/>CONCLUSIONS:<br/>UDCA increases alkaline sphingomyelinase and caspase-3 activities, which might be a mechanism involved in its anticarcinogenic effect on colon cancer development.}},
  author       = {{Cheng, Yajun and Tauschel, Horst-Dietmar and Nilsson, Åke and Duan, Rui-Dong}},
  issn         = {{0036-5521}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{915--920}},
  publisher    = {{Taylor & Francis}},
  series       = {{Scandinavian Journal of Gastroenterology}},
  title        = {{Ursodeoxycholic acid increases the activities of alkaline sphingomyelinase and caspase-3 in the rat colon.}},
  url          = {{http://dx.doi.org/10.1080/003655299750025408}},
  doi          = {{10.1080/003655299750025408}},
  volume       = {{34}},
  year         = {{1999}},
}