کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5829401 1558992 2012 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Molecular and cellular pharmacologyLong-term leptin treatment exerts a pro-apoptotic effect on renal tubular cells via prostaglandin E2 augmentation
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Molecular and cellular pharmacologyLong-term leptin treatment exerts a pro-apoptotic effect on renal tubular cells via prostaglandin E2 augmentation
چکیده انگلیسی

Adipokine leptin reportedly acts on the kidney in pathophysiological states. However, the influence of leptin on renal tubular epithelial cells is still unclear. Gentamicin, a widely used antibiotic for the treatment of bacterial infection, can cause nephrotoxicity. This study aims to investigate the influence of long-term leptin treatment on gentamicin-induced apoptosis in rat renal tubular cells (NRK-52E) and mice. We monitored apoptosis and molecular mechanisms using annexin V/ propidium iodide staining and small interfering RNA transfection. In NRK-52E cells, leptin reduced gentamicin-induced apoptosis at 24 h, but significantly increased apoptosis at 48 h. Long-term treatment of leptin decreased Bcl-xL expression and increased caspase activity in gentamicin-treated NRK-52E cells. Leptin also increased the expression of cyclooxygenase-2 (COX-2) and its product, prostaglandin E2 (PGE2), in a dose-dependent manner. The COX-2 inhibitor, NS398 (N-[2-(Cyclohexyloxy)-4- nitrophenyl]methanesulfonamide), blocked PGE2 augmentation and the pro-apoptotic effects of leptin. The addition of PGE2 recovered the pro-apoptotic effect of leptin in NS398-treated NRK-52E cells. In a mouse animal model, a 10 day leptin treatment significantly increased gentamicin-induced apoptotic cells in proximal tubules. NS398 treatment inhibited this in vivo pro-apoptotic effect of leptin. Results reveal that long-term elevation of leptin induces COX-2-mediated PGE2 augmentation in renal tubular cells, and then increases these cells' susceptibility to gentamicin-induced apoptosis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 689, Issues 1–3, 15 August 2012, Pages 65-71
نویسندگان
, , , , , , ,