کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2596015 1562370 2011 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cysteinyl leukotrienes synthesis is involved in aristolochic acid I-induced apoptosis in renal proximal tubular epithelial cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Cysteinyl leukotrienes synthesis is involved in aristolochic acid I-induced apoptosis in renal proximal tubular epithelial cells
چکیده انگلیسی

Aristolochic acid I (AAI) is a primary nephrotoxin and carcinogen that is found in some Chinese herbal medicines, and AAI is responsible for the progression of aristolochic acid nephropathy. The membrane associated proteins in the eicosanoid and glutathione metabolism (MAPEG) superfamily are associated with cysteinyl leukotrienes (cysLTs) synthesis. The present study investigated whether cysLTs synthesis was involved in AAI-induced renal proximal tubular epithelial cell injury in LLC-PK1 cells. Based on MAPEG and related molecular events, the potential mechanisms of AAI-induced LLC-PK1 cell injury were explored. AAI triggered the mitochondrial/caspase apoptotic pathway in LLC-PK1 cells, which was indicated by an enhanced Bax/Bcl-2 ratio, loss of mitochondrial membrane potential, cytochrome C release, and caspase 3 activation. In addition, AAI-induced cysLTs release was accompanied by selective upregulation of 5-lipoxygenase activating protein (FLAP) and microsomal glutathione S-transferase 3 (mGST3) in a concentration-dependent manner. The FLAP inhibitor MK866 significantly protected cells from AAI-induced apoptosis. Furthermore, activation of extracellular signal-regulated kinase (ERK) 1/2 and inhibition of phosphorylated p38-MAPK were demonstrated at the early phase of AAI treatment. Notably, the MEK/ERK inhibitor U0126 reversed AAI-induced apoptosis and reduced both FLAP, mGST3 and mitochondrial/caspase protein expression. Taken together, these findings suggest that cysLTs synthesis is involved in AAI-induced apoptosis via an ERK activation way.


► AAI induced cysLTs release was accompanied by selectively elevating FLAP and mGST3.
► Enhanced cysLTs synthesis followed by apoptosis after treatment with AAI.
► ERK activation pathway was involved in apoptosis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 287, Issues 1–3, 5 September 2011, Pages 38–45
نویسندگان
, , , , , , , , ,