کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5504401 | 1536285 | 2017 | 57 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Characterization of Acyl-CoA synthetase isoforms in pancreatic beta cells: Gene silencing shows participation of ACSL3 and ACSL4 in insulin secretion
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Long-chain acyl-CoA synthetases (ACSLs) convert fatty acids to fatty acyl-CoAs to regulate various physiologic processes. We characterized the ACSL isoforms in a cell line of homogeneous rat beta cells (INS-1 832/13Â cells) and human pancreatic islets. ACSL4 and ACSL3 proteins were present in the beta cells and human and rat pancreatic islets and concentrated in insulin secretory granules and less in mitochondria and negligible in other intracellular organelles. ACSL1 and ACSL6 proteins were not seen in INS-1 832/13Â cells or pancreatic islets. ACSL5 protein was seen only in INS-1 832/13Â cells. With shRNA-mediated gene silencing we developed stable ACSL knockdown cell lines from INS-1 832/13Â cells. Glucose-stimulated insulin release was inhibited â¼50% with ACSL4 and ACSL3 knockdown and unaffected in cell lines with knockdown of ACSL5, ACLS6 and ACSL1. Lentivirus shRNA-mediated gene silencing of ACSL4 and ACSL3 in human pancreatic islets inhibited glucose-stimulated insulin release. ACSL4 and ACSL3 knockdown cells showed inhibition of ACSL enzyme activity more with arachidonate than with palmitate as a substrate, consistent with their preference for unsaturated fatty acids as substrates. ACSL4 knockdown changed the patterns of fatty acids in phosphatidylserines and phosphatidylethanolamines. The results show the involvement of ACLS4 and ACLS3 in insulin secretion.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Archives of Biochemistry and Biophysics - Volume 618, 15 March 2017, Pages 32-43
Journal: Archives of Biochemistry and Biophysics - Volume 618, 15 March 2017, Pages 32-43
نویسندگان
Israr-ul H. Ansari, Melissa J. Longacre, Scott W. Stoker, Mindy A. Kendrick, Lucas M. O'Neill, Laura J. Zitur, Luis A. Fernandez, James M. Ntambi, Michael J. MacDonald,