کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5558559 | 1561147 | 2017 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The anti-ALS drug riluzole attenuates pericyte loss in the diabetic retinopathy of streptozotocin-treated mice
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: The anti-ALS drug riluzole attenuates pericyte loss in the diabetic retinopathy of streptozotocin-treated mice The anti-ALS drug riluzole attenuates pericyte loss in the diabetic retinopathy of streptozotocin-treated mice](/preview/png/5558559.png)
چکیده انگلیسی
Loss of pericytes, considered an early hallmark of diabetic retinopathy, is thought to involve abnormal activation of protein kinase C (PKC). We previously showed that the anti-amyotrophic lateral sclerosis (ALS) drug riluzole functions as a PKC inhibitor. Here, we examined the effects of riluzole on pathological changes in diabetic retinopathy. Pathological endpoints examined in vivo included the number of pericytes and integrity of retinal vessels in streptozotocin (STZ)-induced diabetic mice. In addition, PKC activation and the induction of monocyte chemotactic protein (MCP1) were assessed in diabetic mice and in human retinal pericytes exposed to advanced glycation end product (AGE) or modified low-density lipoprotein (mLDL). The diameter of retinal vessels and the number of pericytes were severely reduced, and the levels of MCP1 and PKC were increased in STZ-induced diabetic mice. Administration of riluzole reversed all of these changes. Furthermore, the increased expression of MCP1 in AGE- or mLDL-treated cultured retinal pericytes was inhibited by treatment with riluzole or the PKC inhibitor GF109203X. In silico modeling showed that riluzole fits well within the catalytic pocket of PKC. Taken together, our results demonstrate that riluzole attenuates both MCP1 induction and pericyte loss in diabetic retinopathy, likely through its direct inhibitory effect on PKC.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 315, 15 January 2017, Pages 80-89
Journal: Toxicology and Applied Pharmacology - Volume 315, 15 January 2017, Pages 80-89
نویسندگان
Jeong A. Choi, Yoo-Ri Chung, Hyae-Ran Byun, Hwangseo Park, Jae-Young Koh, Young Hee Yoon,