BILE ACIDS AND LARGE BOWEL CARCINOGENESIS
胆汁酸与大肠癌发生
基本信息
- 批准号:3164786
- 负责人:
- 金额:$ 9.08万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1978
- 资助国家:美国
- 起止时间:1978-05-01 至 1987-11-30
- 项目状态:已结题
- 来源:
- 关键词:Clostridium biotransformation carcinogens chenodeoxycholate cholelithiasis dietary constituent enteric bacteria enzyme structure feces gel filtration chromatography host organism interaction hydrolase hydroxylation hydroxysteroid dehydrogenases microorganism culture mutagen testing nutrition related neoplasm /cancer nutrition related tag radiotracer steroid metabolism
项目摘要
There is substantial evidence that microbially generated secondary bile
acids (deoxychollic and lithocholic acid) are co-carcinogenic and these
steroids may facilitate the development, growth and spread of large bowel
cancer. Moreover, bile acids have recently been shown to specifically
stimulate the formation of fecal mutagens (unsaturated glyceryl ether
lipids) by intestinal anaerobic bacteria. The concentration of secondary
bile acids in the large bowel appears to be a function of dietary habits
and bile acids 7-dehydroxylase activity of the intestinal microflora. The
first aim of this grant proposal is the purification, characterization and
regulation of bile acid 7-dehydroxylase from Eubacterium sp. V.P.I. 12708.
Our current approach is to purify the bile acid inducible polypeptides
(23,500, 27,000 56,000 and 77,000 daltons) using SDS-PAGE as a detection
technique. These polypeptides are specifically induced by primary bile
acids and co-purify (except 23,500) with 7-dehydroxylase activity during
HPLC-gel filtration chromatography. Bile acid inducible polypeptides will
be purified by (NH4)2SO4 fractionation, HPLC-DEAE chromatography (2 PH
values), HPLC gel filtration and HPLC-reverse phase (C3) chromatography.
Purified polypeptides will be used for physical characterization studies.
The second aim of this proposal is to raise antibody against bile acid
inducible polypeptides. Specific antibody will be used in
immunoprecipitation studies aimed at determining how many polypeptides make
up bile acid 7-dehydroxylase and if 7Alpha, 7Beta and Delta6-reductase
activities all reside in the same enzyme complex. The third aim will be
the purification and characterization of bile acid binding proteins and to
determine their role in bile acid 7-dehydroxylation. The fourth aim of
this proposal will be to clone bile acid 7-dehydroxylase from Eubacterium
sp. V.P.I. 12708 into E. coli using the expression vector PKG 1800. The
final aim will be to determine the mechanism of conversion of
3Alpha-sulfolithocholic to Delta3-cholenoic acid and 5Beta-cholanoic acid
by Clostridum sordellii and to develop a "cell-free" system that will
catalyze this bile acid biotransformation(s) so that the enzymology and
mechanism of the reaction can be studied in detail.
有大量证据表明微生物产生了次生胆汁
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Modified plasmid isolation method for Clostridium perfringens and Clostridium absonum.
产气荚膜梭状芽胞杆菌和absonum 梭状芽胞杆菌的改良质粒分离方法。
- DOI:10.1128/aem.52.1.197-199.1986
- 发表时间:1986
- 期刊:
- 影响因子:4.4
- 作者:Roberts,I;Holmes,WM;Hylemon,PB
- 通讯作者:Hylemon,PB
HPLC purification and preparation of antibodies to cholic acid-inducible polypeptides from Eubacterium sp. V.P.I. 12708.
HPLC 纯化和制备针对真杆菌属胆酸诱导多肽的抗体。
- DOI:
- 发表时间:1984
- 期刊:
- 影响因子:6.5
- 作者:Paone,DA;Hylemon,PB
- 通讯作者:Hylemon,PB
Molecular cloning of bile acid 7-dehydroxylase from Eubacterium sp. strain VPI 12708.
真杆菌属胆汁酸 7-脱羟酶的分子克隆。
- DOI:10.1128/jb.169.4.1516-1521.1987
- 发表时间:1987
- 期刊:
- 影响因子:3.2
- 作者:Coleman,JP;White,WB;Hylemon,PB
- 通讯作者:Hylemon,PB
Biosynthesis of a novel bile acid nucleotide and mechanism of 7 alpha-dehydroxylation by an intestinal Eubacterium species.
新型胆汁酸核苷酸的生物合成和肠道真杆菌属 7α-脱羟基的机制。
- DOI:
- 发表时间:1987
- 期刊:
- 影响因子:0
- 作者:Coleman,JP;White,WB;Egestad,B;Sjövall,J;Hylemon,PB
- 通讯作者:Hylemon,PB
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PHILLIP B HYLEMON其他文献
PHILLIP B HYLEMON的其他文献
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{{ truncateString('PHILLIP B HYLEMON', 18)}}的其他基金
LncRNA H19 in Cholestatic Liver Diseases
LncRNA H19 在胆汁淤积性肝病中的作用
- 批准号:
10202570 - 财政年份:2018
- 资助金额:
$ 9.08万 - 项目类别:
LncRNA H19 in Cholestatic Liver Diseases
LncRNA H19 在胆汁淤积性肝病中的作用
- 批准号:
10909545 - 财政年份:2018
- 资助金额:
$ 9.08万 - 项目类别:
LncRNA H19 in Cholestatic Liver Diseases
LncRNA H19 在胆汁淤积性肝病中的作用
- 批准号:
9750721 - 财政年份:2018
- 资助金额:
$ 9.08万 - 项目类别:
Bile Acid and Sphingosine-1-phosphate Receptor-mediated Signaling in Cholestasis
胆汁酸和 1-磷酸鞘氨醇受体介导的胆汁淤积信号传导
- 批准号:
9024718 - 财政年份:2015
- 资助金额:
$ 9.08万 - 项目类别:
Role of Bile Acids and Gut Bacteria in GI Diseases
胆汁酸和肠道细菌在胃肠道疾病中的作用
- 批准号:
8698288 - 财政年份:2012
- 资助金额:
$ 9.08万 - 项目类别:
Role of Bile Acids and Gut Bacteria in GI Diseases
胆汁酸和肠道细菌在胃肠道疾病中的作用
- 批准号:
8536579 - 财政年份:2012
- 资助金额:
$ 9.08万 - 项目类别:
Bile Acids and Clostridium scindens Inhibit C. difficile: Role of Secreted Antibacterial Compounds
胆汁酸和梭菌抑制艰难梭菌:分泌的抗菌化合物的作用
- 批准号:
9233344 - 财政年份:2012
- 资助金额:
$ 9.08万 - 项目类别:
Role of Bile Acids and Gut Bacteria in GI Diseases
胆汁酸和肠道细菌在胃肠道疾病中的作用
- 批准号:
8324091 - 财政年份:2012
- 资助金额:
$ 9.08万 - 项目类别:
HIV Protease Inhibitors and Hepatic Lipid Dysregulation
HIV 蛋白酶抑制剂和肝脂质失调
- 批准号:
7035831 - 财政年份:2004
- 资助金额:
$ 9.08万 - 项目类别:
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