کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5504896 | 1400256 | 2017 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Metformin protects against retinal cell death in diabetic mice
ترجمه فارسی عنوان
متفورمین در برابر مرگ سلولی شبکیه در موشهای دیابتی محافظت می کند
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
چکیده انگلیسی
Retinal degeneration is an early feature of diabetic retinopathy, the major cause of blindness in the developed world. Here we investigated how the widely used antidiabetic drug metformin reduces retinal injury in diabetic mice. Metformin was orally administered to control mice or mice with streptozotocin-induced diabetes. Western blot analysis showed that levels of O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) and other related proteins such as carbohydrate-responsive element-binding protein (ChREBP) and thioredoxin-interacting protein (TXNIP) were significantly increased, and nuclear factor kappaB (NF-κB) and poly (ADP-ribose) polymerase (PARP) were activated in the diabetic retinas or retinal pigment epithelial (RPE) cells exposed to high glucose compared to controls. More importantly, RPE cells exposed to high glucose and treated with thiamet-G had higher levels of those proteins, demonstrating the role of elevated O-GlcNAcylation. Double immunofluorescence analysis revealed increased co-localization of terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL)-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB in diabetic retinas compared to control retinas. Co-immunoprecipitation analysis showed that interaction between OGT and ChREBP or NF-κB was increased in diabetic retinas compared to control retinas, and this was accompanied by more cell death. Notably, metformin attenuated the increases in protein levels; reduced co-localization of TUNEL-positive ganglion cells and OGT, ChREBP, TXNIP, or NF-κB; and reduced interaction between OGT and ChREBP or NF-κB. Our results indicate that OGT inhibition might be one of the mechanisms by which metformin decreases retinal cell death.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 492, Issue 3, 21 October 2017, Pages 397-403
Journal: Biochemical and Biophysical Research Communications - Volume 492, Issue 3, 21 October 2017, Pages 397-403
نویسندگان
Yoon Sook Kim, Minjun Kim, Mee Young Choi, Dong Hoon Lee, Gu Seob Roh, Hyun Joon Kim, Sang Soo Kang, Gyeong Jae Cho, Seong-Jae Kim, Ji-Myong Yoo, Wan Sung Choi,