Modulation of human Niemann-Pick C1-like 1 gene expression by sterol: Role of sterol regulatory element binding protein 2.

Modulation of human Niemann-Pick C1-like 1 gene expression by sterol: Role of sterol regulatory element binding protein 2. Research Abstract Details 

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Modulation of human Niemann-Pick C1-like 1 gene expression by sterol: Role of sterol regulatory element binding protein 2. Abstract Text:

Waddah A Alrefai,Fadi Annaba,Zaheer Sarwar,Alka Dwivedi,Seema Saksena,Amika Singla,Pradeep K Dudeja,Ravinder K Gill,

Niemann-Pick C1-like 1 (NPC1L1) is an essential intestinal component of cholesterol absorption. However, little is known about the molecular regulation of intestinal NPC1L1 expression and promoter activity. We demonstrated that human NPC1L1 mRNA expression was significantly decreased by 25-hydroxycholesterol but increased in response to cellular cholesterol depletion achieved by incubation with Mevinolin (an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase) in human intestinal Caco-2 cells. We also showed that a -1741/+56 fragment of the NPC1L1 gene demonstrated high promoter activity in Caco-2 cells that was reduced by 25-hydroxycholesterol and stimulated by cholesterol depletion. Interestingly, we showed that the NPC1L1 promoter is remarkably transactivated by the overexpression of sterol regulatory element (SRE) binding protein (SREBP)-2, suggesting its involvement in the sterol-induced alteration in NPC1L1 promoter activity. Finally, we identified two putative SREs in the human NPC1L1 promoter and established their essential roles in mediating the effects of cholesterol on promoter activity. Our study demonstrated the modulation of human NPC1L1 expression and promoter activity by cholesterol in a SREBP-2-dependent mechanism.

Modulation of human Niemann-Pick C1-like 1 gene expression by sterol: Role of sterol regulatory element binding protein 2. Publishing Authors By Initials

WA Alrefai,F Annaba,Z Sarwar,A Dwivedi,S Saksena,A Singla,PK Dudeja,RK Gill,

For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

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Modulation of human Niemann-Pick C1-like 1 gene expression by sterol: Role of sterol regulatory element binding protein 2. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: American journal of physiology. Gastrointestinal a

VOLUME: 292

Page Numbers: G369-76

Journal Abbreviation: Am. J. Physiol. Gastrointest.

ISSN: 0193-1857

DAY: 28

MONTH: 09

YEAR: 2006

Modulation of human Niemann-Pick C1-like 1 gene expression by sterol: Role of sterol regulatory element binding protein 2. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100901227

Modulation of human Niemann-Pick C1-like 1 gene expression by sterol: Role of sterol regulatory element binding protein 2. Keywords Mesh Terms:

KEYWORDS: Transfection

MESH TERMS: physiology

Chemical & Substance for Abstract: Modulation of human Niemann-Pick C1-like 1 gene expression by sterol: Role of sterol regulatory element binding protein 2. Information

Substance Name: Cholesterol

Registry Number: 57-88-5

Grant and Affiliation Information for Modulation of human Niemann-Pick C1-like 1 gene expression by sterol: Role of sterol regulatory element binding protein 2.

AFFILIATION: Section of Digestive Diseases and Nutrition, Department of Medicine, University of Illinois, and Jesse Brown Veterans Affairs Medical Center, Chicago, IL 60612, USA. walrefai@uic.edu

Country: United States

AGENCY: United States NIDDK

GRANT: DK-71596

ACRONYM: DK

MEDLINETA: Am J Physiol Gastrointest Live

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