کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5829674 | 1558998 | 2012 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Adenosine A1 receptors do not play a major role in the regulation of lipogenic gene expression in hepatocytes
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
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چکیده انگلیسی
Activation of adenosine A1 receptors was reported to promote fatty acid synthesis in AML-12 cells, by increasing the expression of SREBP-1c (sterol regulatory binding protein 1c) and FAS (fatty acid synthase). Since these findings have important therapeutic implications for the discovery of adenosine A1 receptor agonists, further studies were undertaken to determine the expression and functional relevance of adenosine A1 receptor in the liver. To that end, we used two classes of distinct adenosine A1 receptor agonists: CPA (N6-cyclopentyl-adenosine), a full agonist and GS-9667 (2-{6-[((1R,2R)-2-hydroxycyclopentyl)-amino]purin-9-yl}(4S,5S,2R,3R)-5-[(2-fluorophenylthio)methyl]-oxolane-3,4-diol), a partial agonist. Treatment of AML-12 cells, HepG2 cells and primary human hepatocytes with either CPA or GS-9667 did not increase the gene expression of SREBP-1c or FAS. Furthermore, in AML-12 and HepG2 cells, CPA did not antagonize forskolin-stimulated cAMP production, a characteristic of adenosine A1 receptor activation, indicating that these cells lack adenosine A1 receptor function. Consistent with this finding, adenosine A1 receptor gene expression was found to be very low and adenosine A1 receptor protein levels were hardly detectable by radioligand binding assays in hepatic cell lines such as AML-12 and HepG2 as well as in both mouse and human liver tissues. Finally, acute treatment with adenosine A1 receptor agonist GS-9667 had no significant effect on gene expression of both SREBP-1c and FAS in livers of Sprague Dawley rats. Taken together, our data suggest that the expression of adenosine A1 receptor is too low to play a major role in the regulation of lipogenic gene expression in hepatocytes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 683, Issues 1â3, 15 May 2012, Pages 332-339
Journal: European Journal of Pharmacology - Volume 683, Issues 1â3, 15 May 2012, Pages 332-339
نویسندگان
Ming Yang, Ruth Chu, Jeffrey W. Chisholm, Holger Doege, Luiz Belardinelli, Arvinder K. Dhalla,