| Activated polyamine catabolism leads to low cholesterol levels by enhancing bile acid synthesis. | |
| | |
MedLine Citation:
|
PMID: 19956992 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Transgenic mice with activated polyamine catabolism due to overexpression of spermidine/spermine N(1)-acetyltransferase (SSAT) have significantly reduced plasma total cholesterol levels. In our study, we show that low cholesterol levels were attributable to enhanced bile acid synthesis in combination with reduced cholesterol absorption. Hepatic cholesterol 7alpha-hydroxylase (CYP7A1), the rate-limiting enzyme catalyzing the conversion of cholesterol to bile acids, plays an important role in the removal of excess cholesterol from the body. We suggest that by reducing activity of Akt activated polyamine catabolism increased the stability and activity of peroxisome proliferator-activated receptor gamma co-activator 1alpha, the critical activator of CYP7A1. This is supported by our finding that the treatment with SSAT activator, N (1) ,N(11)-diethylnorspermine, reduced significantly the amount of phosphorylated (active) Akt in HepG2 cells. In summary, activated-polyamine catabolism is a novel mechanism to regulate bile acid synthesis. Therefore, polyamine catabolism could be a potential therapeutic target to control hepatic CYP7A1 expression. |
| | |
Authors:
|
Eija Pirinen; Helena Gylling; Paula Itkonen; Nagendra Yaluri; Sami Heikkinen; Marko Pietil?; Teemu Kuulasmaa; Maija Tusa; Marc Cerrada-Gimenez; Jussi Pihlajam?ki; Leena Alhonen; Juhani J?nne; Tatu A Miettinen; Markku Laakso |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-03 |
Journal Detail:
|
Title: Amino acids Volume: 38 ISSN: 1438-2199 ISO Abbreviation: Amino Acids Publication Date: 2010 Feb |
Date Detail:
|
Created Date: 2010-02-09 Completed Date: 2010-06-02 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9200312 Medline TA: Amino Acids Country: Austria |
Other Details:
|
Languages: eng Pagination: 549-60 Citation Subset: IM |
Affiliation:
|
Department of Medicine, University of Kuopio, P.O. Box 1777, 70211, Kuopio, Finland. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acetyltransferases
/
genetics,
metabolism Animals Bile Acids and Salts / biosynthesis* Biogenic Polyamines / biosynthesis* Cholesterol / blood* Cholesterol 7-alpha-Hydroxylase / genetics, metabolism Female Hep G2 Cells Liver / enzymology, metabolism Male Mice Mice, Inbred BALB C Mice, Inbred DBA Mice, Transgenic |
| Chemical | |
Reg. No./Substance:
|
0/Bile Acids and Salts; 0/Biogenic Polyamines; 57-88-5/Cholesterol; EC 1.14.13.17/Cholesterol 7-alpha-Hydroxylase; EC 2.3.1.-/Acetyltransferases; EC 2.3.1.57/diamine N-acetyltransferase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: alpha-Methylspermidine protects against carbon tetrachloride-induced hepatic and pancreatic damage.
Next Document: Evaluation method for polyamine uptake by N (1)-dansylspermine.