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

2007 ◽  
Author(s):  
Bruno Stieger
Keyword(s):  
Gene Expression ◽  
Binding Protein ◽  
Regulatory Element ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Niemann Pick

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

2007 ◽  
Vol 292 (1) ◽  
pp. G369-G376 ◽  
Author(s):  
Waddah A. Alrefai ◽  
Fadi Annaba ◽  
Zaheer Sarwar ◽  
Alka Dwivedi ◽  
Seema Saksena ◽  
...  
Keyword(s):  
Promoter Activity ◽  
Binding Protein ◽  
Regulatory Element ◽  
Cholesterol Absorption ◽  
Cholesterol Depletion ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Niemann Pick ◽  
Coa Reductase

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.

Regulation of sterol regulatory-element binding protein 1 gene expression in liver: role of insulin and protein kinase B/cAkt

2000 ◽  
Vol 349 (1) ◽  
pp. 13-17 ◽  
Author(s):  
Mark FLEISCHMANN ◽  
Patrick B. IYNEDJIAN
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Recombinant Protein ◽  
Protein Kinase B ◽  
Binding Protein ◽  
Regulatory Element ◽  
Mutant Form ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Insulin stimulates the transcription of the sterol regulatory- element binding protein (SREBP) 1/ADD1 gene in liver. Hepatocytes in primary culture were used to delineate the insulin signalling pathway for induction of SREBP1 gene expression. The inhibitors of phosphoinositide 3-kinase (PI 3-kinase), wortmannin and LY 294002, abolished the insulin-dependent increase in SREBP1 mRNA, whereas the inhibitor of the mitogen- activated protein kinase cascade, PD 98059, was without effect. To investigate the role of protein kinase B (PKB)/cAkt downstream of PI 3-kinase, hepatocytes were transduced with an adenovirus encoding a PKB-oestrogen receptor fusion protein. The PKB activity of this recombinant protein was rapidly activated in hepatocytes challenged with 4-hydroxytamoxifen (OHT), as was endogenous PKB in hepatocytes challenged with insulin. The addition of OHT to transduced hepatocytes resulted in accumulation of SREBP1 mRNA, with a time-course and magnitude similar to the effect of insulin in non-transduced cells. The level of SREBP1 mRNA was not increased by OHT in hepatocytes expressing a mutant form of the recombinant protein whose PKB activity was not activated by OHT. Thus acute activation of PKB is sufficient to induce SREBP1 mRNA accumulation in primary hepatocytes, and might be the major signalling event by which insulin induces SREBP1 gene expression in the liver.

scholarly journals Sterol Regulatory Element-binding Protein-2- and Liver X Receptor-driven Dual Promoter Regulation of Hepatic ABC Transporter A1 Gene Expression

2007 ◽  
Vol 282 (29) ◽  
pp. 21090-21099 ◽  
Author(s):  
Norimasa Tamehiro ◽  
Yukari Shigemoto-Mogami ◽  
Tomoshi Kakeya ◽  
Kei-ichiro Okuhira ◽  
Kazuhiro Suzuki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Abc Transporter ◽  
Binding Protein ◽  
Regulatory Element ◽  
Liver X Receptor ◽  
Promoter Regulation ◽  
Element Binding Protein ◽  
Sterol Regulatory Element ◽  
Dual Promoter

scholarly journals Transcription Factor Sterol Regulatory Element Binding Protein 2 Regulates Scavenger Receptor Cla-1 Gene Expression

2004 ◽  
Vol 24 (12) ◽  
pp. 2358-2364 ◽  
Author(s):  
Morgan Tréguier ◽  
Chantal Doucet ◽  
Martine Moreau ◽  
Christiane Dachet ◽  
Joëlle Thillet ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Binding Protein ◽  
Regulatory Element ◽  
Scavenger Receptor ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

scholarly journals Human Sterol Regulatory Element-Binding Protein 1a Contributes Significantly to Hepatic Lipogenic Gene Expression

2015 ◽  
Vol 35 (2) ◽  
pp. 803-815 ◽  
Author(s):  
Andreas Bitter ◽  
Andreas K. Nüssler ◽  
Wolfgang E. Thasler ◽  
Kathrin Klein ◽  
Ulrich M. Zanger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Liver ◽  
Target Genes ◽  
Binding Protein ◽  
Regulatory Element ◽  
Lipogenic Gene ◽  
Knock Down ◽  
Lipogenic Gene Expression ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Background/Aims: Sterol regulatory element-binding protein (SREBP) 1, the master regulator of lipogenesis, was shown to be associated with non-alcoholic fatty liver disease, which is attributed to its major isoform SREBP1c. Based on studies in mice, the minor isoform SREBP1a is regarded as negligible for hepatic lipogenesis. This study aims to elucidate the expression and functional role of SREBP1a in human liver. Methods: mRNA expression of both isoforms was quantified in cohorts of human livers and primary human hepatocytes. Hepatocytes were treated with PF-429242 to inhibit the proteolytic activation of SREBP precursor protein. SREBP1a-specifc and pan-SREBP1 knock-down were performed by transfection of respective siRNAs. Lipogenic SREBP-target gene expression was analyzed by real-time RT-PCR. Results: In human liver, SREBP1a accounts for up to half of the total SREBP1 pool. Treatment with PF-429242 indicated SREBP-dependent auto-regulation of SREBP1a, which however was much weaker than of SREBP1c. SREBP1a-specifc knock-down also reduced significantly the expression of SREBP1c and of SREBP-target genes. Regarding most SREBP-target genes, simultaneous knock-down of both isoforms resulted in effects of only similar extent as SREBP1a-specific knock-down. Conclusion: We here showed that SREBP1a is significantly contributing to the human hepatic SREBP1 pool and has a share in human hepatic lipogenic gene expression.

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