کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10815087 | 1058448 | 2014 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
New insights concerning insulin synthesis and its secretion in rat hippocampus and cerebral cortex: Amyloid-β1-42-induced reduction of proinsulin level via glycogen synthase kinase-3β
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کلمات کلیدی
RT-PCRGSK-3βCAPS2Amyloid-β1–42Aβ1–42 - Aβ1-42DMSO - DMSOAlzheimer's disease - بیماری آلزایمرDimethyl sulfoxide - دیمتیل سولفواکسیدpHluorin - فلوئورینCerebrospinal fluid - مایع مغزی نخاعیCSF - مایع مغزی نخاعیHippocampal neurons - نورونهای هیپوکامپreverse transcriptase polymerase chain reaction - واکنش زنجیره ای پلی مراز ترانس کریتاز معکوسProinsulin - پروینسولینGlycogen synthase kinase-3β - گلیکوزین سنتاز کیناز 3β
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The reduction of insulin levels in hippocampal areas is associated with Alzheimer's disease. The present study using rat brain explores the mechanisms of insulin synthesis and secretion, as well as amyloid-β1-42 (Aβ1-42)-induced reduction of proinsulin expression. After confirming the expression of insulin mRNA and proinsulin in rat brain, we visualized and analyzed the motion of insulin secretion in rat hippocampal neurons using pH-sensitive green fluorescent protein (pHluorin) fused to the insulin. In the rat hippocampal neurons expressing insulin-pHluorin, time-lapse confocal laser scanning microscopy revealed the appearance of fluorescent spots induced by depolarization after stimulation with 50 mM KCl. In these fluorescent spots, Ca2 +-dependent activator protein for secretion 2 (CAPS2), which is the regulator of the dense-core vesicle involving neuronal peptides, was co-localized with insulin-pHluorin. However, Aβ1-42-induced reduction of proinsulin in rat hippocampal neurons was inhibited by treatment with lithium and transfection with glycogen synthase kinase-3β (GSK-3β) siRNA. These results demonstrate that synthesized insulin is secreted from rat hippocampal and cortical neuron's dense-core vesicles, and that activation of GSK-3β in Aβ1-42-induced Alzheimer's model hippocampal neurons decreases the insulin synthesis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 26, Issue 2, February 2014, Pages 253-259
Journal: Cellular Signalling - Volume 26, Issue 2, February 2014, Pages 253-259
نویسندگان
Takayuki Nemoto, Fumiyo Toyoshima-Aoyama, Toshihiko Yanagita, Toyoaki Maruta, Hiroshi Fujita, Tomohiro Koshida, Tetsu Yonaha, Akihiko Wada, Akira Sawaguchi, Manabu Murakami,