کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2603802 1133838 2008 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Proteomic analysis of phospholipidosis in citalopram treated U937 cells – Support for the cholesterol biosynthesis hypothesis
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Proteomic analysis of phospholipidosis in citalopram treated U937 cells – Support for the cholesterol biosynthesis hypothesis
چکیده انگلیسی

Excessive accumulation of phospholipids leads to phospholipidosis (PL), which disrupts cellular functions, in extreme cases leading to acute or chronic disease. Citalopram and many other cationic amphiphilic drugs (CADs) have been shown to cause PL both in vitro and in vivo. Recent toxicogenomic studies suggest four hypothetical mechanisms for PL (lysosomal enzyme transport decrease, lysosomal phospholipase activity decrease, phospholipids biosynthesis increase or cholesterol biosynthesis increase). However, the post-genomic steps remain largely unknown and proteomic analyses hold significant promise for defining mechanisms of PL induction. In this study U937 monoblastoid cells were exposed to citalopram hydrobromide for 24 h (0, 20, 100 or 200 μM as citalopram free base) and then harvested for whole cell proteomic analysis using 2-D gel electrophoresis, or transmission electron microscopy (TEM). Protein spots that were significantly altered versus controls were analysed by MALDI-TOF mass spectrometry. Up-regulated proteins were Glyoxalase-I (Glo 1) and 3-Hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (HMGCS1) in cells with PL shown by TEM (favouring the cholesterol biosynthesis increase hypothesis for citalopram induced PL). Other altered proteins were catalase (up-regulated), beta-actin (up-regulated) and 14-3-3 protein (down-regulated). The function of several of the successfully identified proteins indicates a potential perturbed lipid metabolism.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology in Vitro - Volume 22, Issue 5, August 2008, Pages 1198–1204
نویسندگان
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