ABCC8 p.Arg1379Leu
| Predicted by SNAP2: | A: D (91%), C: D (91%), D: D (95%), E: D (95%), F: D (95%), G: D (95%), H: D (91%), I: D (95%), K: D (91%), L: D (95%), M: D (91%), N: D (95%), P: D (95%), Q: D (91%), S: D (91%), T: D (95%), V: D (95%), W: D (95%), Y: D (95%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, S: D, T: D, V: D, W: D, Y: D, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] 17beta-Estradiol modulates apoptosis in pancreatic... J Biol Chem. 2009 Feb 20;284(8):4905-13. Epub 2008 Dec 18. Ackermann S, Hiller S, Osswald H, Losle M, Grenz A, Hambrock A
17beta-Estradiol modulates apoptosis in pancreatic beta-cells by specific involvement of the sulfonylurea receptor (SUR) isoform SUR1.
J Biol Chem. 2009 Feb 20;284(8):4905-13. Epub 2008 Dec 18., [PMID:19095654]
Abstract [show]
Apoptosis of pancreatic beta-cells is an important factor in the pathophysiology of diabetes. Previously, we have shown that the "phytoestrogen" resveratrol can induce beta-cell apoptosis dependent on the expression of sulfonylurea receptor (SUR) 1, the regulatory subunit of pancreatic ATP-sensitive K(+) channels. Here, we investigate whether 17beta-estradiol also influences beta-cell apoptosis in a SUR1-dependent manner. Therefore, islets from wild type or SUR1 knock-out mice, clonal beta-cells, or HEK293 cells expressing different SUR forms were treated with 17beta-estradiol or estrone. Different apoptotic parameters were determined and estrogen binding to SUR was analyzed. In murine islets, 17beta-estradiol treatment resulted in significant apoptotic changes, which in their nature (either apoptotic or anti-apoptotic) were dependent on the age of the animal. These effects were not observed in SUR1 knock-out mice. Furthermore, 17beta-estradiol, which specifically binds to SUR, induced enhanced apoptosis in SUR1-expressing HEK293 cells and clonal beta-cells, whereas apoptosis in recombinant cells expressing SUR2A or SUR2B (cardiac or vascular SUR-isoforms) or sham-transfected control cells was significantly lower. The apoptotic potency of 17beta-estradiol was much higher than that of resveratrol or estrone. SUR1-specific 17beta-estradiol-induced apoptosis was either abolished by the mutation M1289T in transmembrane helix 17 of SUR1 or clearly enhanced by two mutations in nucleotide binding fold 2 (R1379C, R1379L). In conclusion, 17beta-estradiol treatment modulates beta-cell apoptosis under specific involvement of SUR1 in an age-dependent manner. 17beta-Estradiol-induced apoptosis can be influenced by certain SUR1 mutations. These findings may contribute to the understanding of pathophysiological changes in beta-cell mass and could, for instance, provide interesting aspects concerning the etiology of gestational diabetes.
Comments [show]
None has been submitted yet.
No. Sentence Comment
9 SUR1-specific 17beta-estradiol-induced apoptosis was either abolished by the mutation M1289T in transmembrane helix 17 of SUR1 or clearly enhanced by two mutations in nucleotide binding fold 2 (R1379C, R1379L).
X
ABCC8 p.Arg1379Leu 19095654:9:202
status: NEW43 In addition, we explored in which manner the action of 17beta-estradiol was influenced by mutations (M1289T, R1379C, R1379L) in the SUR1 gene (ABCC8) that are of special importance for SUR function (18-20).
X
ABCC8 p.Arg1379Leu 19095654:43:117
status: NEW46 EXPERIMENTAL PROCEDURES Mutagenesis, Transfection, and Cell Culture-HEK293 cells (German Collection of Microorganisms and Cell Cultures, DSMZ, Braunschweig, Germany) were stably transfected with pcDNA3.1 expression vector (Invitrogen) containing the coding sequence of rat SUR1 (GenBankTM accession number X97279), SUR1(M1289T), SUR1(R1379C), SUR1(R1379L), murine SUR2A (GenBank D86037), SUR2A(Y1206S), murine SUR2B (GenBank D86038), or SUR2B(Y1206S), or they were transfected with empty pcDNA3.1 expression vector (Invitrogen).
X
ABCC8 p.Arg1379Leu 19095654:46:348
status: NEW105 By contrast, apoptosis in cells expressing mutants SUR1(R1379C) or SUR1(R1379L) was potentiated to a large extent (Figs.
X
ABCC8 p.Arg1379Leu 19095654:105:72
status: NEW120 After treatment of SUR1-, SUR1(M1289T)-, SUR2A-, and SUR2B-expressing HEK293 cells (A and B) or of SUR1, SUR1(R1379C), and SUR1(R1379L) cells (C) with 17beta-estradiol (100 mol/liter, 24 h), cell detachmentorchangesinnuclearmorphologyweredeterminedandcomparedwiththeresultsobtainedwith pcDNA control cells (please note the different scales in A and C).
X
ABCC8 p.Arg1379Leu 19095654:120:128
status: NEW184 This SUR1-dependent effect of 17beta-estradiol is either abolished by mutation M1289T or enhanced by mutations R1379C or R1379L in SUR1.
X
ABCC8 p.Arg1379Leu 19095654:184:121
status: NEW225 The mutation M1289T completely abolishes the SUR1-specific apoptotic effects of KATP channel blockers glibenclamide (3) or resveratrol (4), or 17beta-estradiol obviously without directly affecting binding of these substances to SUR1.
X
ABCC8 p.Arg1379Leu 19095654:225:118
status: NEW227 To see whether SUR1-mediated apoptosis is linked with ATP hydrolysis, we explored the effects of mutations R1379C and R1379L in nucleotide binding fold 2 of SUR1 on 17beta-estradiol action.
X
ABCC8 p.Arg1379Leu 19095654:227:118
status: NEW44 In addition, we explored in which manner the action of 17beta-estradiol was influenced by mutations (M1289T, R1379C, R1379L) in the SUR1 gene (ABCC8) that are of special importance for SUR function (18-20).
X
ABCC8 p.Arg1379Leu 19095654:44:117
status: NEW47 EXPERIMENTAL PROCEDURES Mutagenesis, Transfection, and Cell Culture-HEK293 cells (German Collection of Microorganisms and Cell Cultures, DSMZ, Braunschweig, Germany) were stably transfected with pcDNA3.1 expression vector (Invitrogen) containing the coding sequence of rat SUR1 (GenBankTM accession number X97279), SUR1(M1289T), SUR1(R1379C), SUR1(R1379L), murine SUR2A (GenBank D86037), SUR2A(Y1206S), murine SUR2B (GenBank D86038), or SUR2B(Y1206S), or they were transfected with empty pcDNA3.1 expression vector (Invitrogen).
X
ABCC8 p.Arg1379Leu 19095654:47:348
status: NEW104 By contrast, apoptosis in cells expressing mutants SUR1(R1379C) or SUR1(R1379L) was potentiated to a large extent (Figs. 3C and 4A): compared with SUR1, cell detachment was increased by a factor of 3.0 or 2.7, respectively, and the rate of apoptotic nuclei was elevated b07;3-fold.
X
ABCC8 p.Arg1379Leu 19095654:104:72
status: NEW118 After treatment of SUR1-, SUR1(M1289T)-, SUR2A-, and SUR2B-expressing HEK293 cells (A and B) or of SUR1, SUR1(R1379C), and SUR1(R1379L) cells (C) with 17beta-estradiol (100 òe;mol/liter, 24 h), cell detachmentorchangesinnuclearmorphologyweredeterminedandcomparedwiththeresultsobtainedwith pcDNA control cells (please note the different scales in A and C).
X
ABCC8 p.Arg1379Leu 19095654:118:128
status: NEW182 This SUR1-dependent effect of 17beta-estradiol is either abolished by mutation M1289T or enhanced by mutations R1379C or R1379L in SUR1.
X
ABCC8 p.Arg1379Leu 19095654:182:121
status: NEW106 By contrast, apoptosis in cells expressing mutants SUR1(R1379C) or SUR1(R1379L) was potentiated to a large extent (Figs.
X
ABCC8 p.Arg1379Leu 19095654:106:72
status: NEW121 After treatment of SUR1-, SUR1(M1289T)-, SUR2A-, and SUR2B-expressing HEK293 cells (A and B) or of SUR1, SUR1(R1379C), and SUR1(R1379L) cells (C) with 17beta-estradiol (100 òe;mol/liter, 24 h), cell detachmentorchangesinnuclearmorphologyweredeterminedandcomparedwiththeresultsobtainedwith pcDNA control cells (please note the different scales in A and C).
X
ABCC8 p.Arg1379Leu 19095654:121:128
status: NEW186 This SUR1-dependent effect of 17beta-estradiol is either abolished by mutation M1289T or enhanced by mutations R1379C or R1379L in SUR1.
X
ABCC8 p.Arg1379Leu 19095654:186:121
status: NEW229 To see whether SUR1-mediated apoptosis is linked with ATP hydrolysis, we explored the effects of mutations R1379C and R1379L in nucleotide binding fold 2 of SUR1 on 17beta-estradiol action.
X
ABCC8 p.Arg1379Leu 19095654:229:118
status: NEW