کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1910329 | 1046765 | 2009 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
BMP6 attenuates oxidant injury in HK-2 cells via Smad-dependent HO-1 induction
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
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چکیده انگلیسی
Oxidative stress is involved in a variety of kidney diseases, and heme oxygenase 1 (HO-1) induction is a protective response to oxidative stress. Downregulation of bone morphogenetic protein 6 (BMP6) is associated with renal damage in intrauterine growth-restricted newborns. However, it is unknown whether BMP6 has a renoprotective effect or HO-1 induction property. In this study, we demonstrate that BMP6 effectively protects renal proximal tubule cells (HK-2) against hydrogen peroxide (H2O2)-induced cell injury. BMP6 also increased HO-1 gene expression and activity of HO. Inhibition of de novo gene expression, the HO inhibitor ZnPPIX, HO-1 knockdown, or the carbon monoxide (CO) scavenger hemoglobin attenuated the cytoprotective effect of BMP6, whereas HO-1 constitutive expression, the HO-1 inducer hemin, or the hemin metabolites bilirubin and CO ameliorated H2O2-induced cell injury. Stimulation of HK-2 cells with BMP6 activated Smad signaling but not mitogen-activated protein kinases. In addition, BMP6-mediated induction of HO-1 expression and increase in HO activity were inhibited by Smad5 knockdown. Furthermore, deletion or mutation of the Smad-binding element in the HO-1 promoter also inhibited BMP6-induced luciferase activity. In summary, these findings suggest that induction of HO-1 through a Smad-dependent mechanism is responsible for the cytoprotective effect of BMP6 in H2O2-mediated renal cell injury.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 46, Issue 9, 1 May 2009, Pages 1275-1282
Journal: Free Radical Biology and Medicine - Volume 46, Issue 9, 1 May 2009, Pages 1275-1282
نویسندگان
Jidong Yan, Shuang Yang, Jie Zhang, Chunli Zhai, Tianhui Zhu,