کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8476884 | 1550861 | 2015 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibition of c-Src/p38 MAPK pathway ameliorates renal tubular epithelial cells apoptosis in db/db mice
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Inhibition of c-Src/p38 MAPK pathway ameliorates renal tubular epithelial cells apoptosis in db/db mice Inhibition of c-Src/p38 MAPK pathway ameliorates renal tubular epithelial cells apoptosis in db/db mice](/preview/png/8476884.png)
چکیده انگلیسی
Renal tubular epithelial cells (RTEC) apoptosis, which plays a key role in the pathogenesis and progression of diabetic nephropathy (DN), is believed to be contributive to the hyperglycemia-induced kidney failure, though the exact mechanisms remain elusive. In this study, we investigated how inhibition of c-Src/p38 MAPK pathway would affect RTEC apoptosis. The c-Src inhibitor PP2 i.p. administered every other day for 8 weeks to diabetic db/db mice significantly reduced their kidney weights, daily urinary volumes, blood glucose, blood urea nitrogen, serum creatinine, triglyceride and urine albumin excretion, whereas deactivation of c-Src and p38 MAPK were also observed, along with decreases in both Bax/Bcl-2 ratio and cleaved caspase-3 level in the kidneys. In vitro, exposure of HK-2 cells (a human RTEC line), to high glucose (HG) promoted phosphorylation of c-Src and p38 MAPK, and subsequently, as revealed by western blotting, TUNEL assay and flow cytometry, increased cell death, which can be inhibited by PP2. Especially, a specific p38 MAPK inhibitor, SB203580, that both attenuated HG-induced c-Src activation and abrogated the expression of PPARγ and CHOP, also reduced apoptosis. Taken together, PP2 inhibits c-Src and therefore reduces apoptosis in RTEC, which at least in part, is due to suppressed p38 MAPK activation in diabetic kidney.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Endocrinology - Volume 417, 5 December 2015, Pages 27-35
Journal: Molecular and Cellular Endocrinology - Volume 417, 5 December 2015, Pages 27-35
نویسندگان
Haijiang Wu, Yonghong Shi, Xinna Deng, Ye Su, Chunyang Du, Jinying Wei, Yunzhuo Ren, Ming Wu, Yanjuan Hou, Huijun Duan,