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  • Title: Transforming growth factor beta1 mediates apoptotic activity of angiotensin II type I receptor blocker on prostate epithelium in vitro.
    Author: Zhao Y, Peng J, Zheng L, Yu W, Jin J.
    Journal: Prostate; 2010 Jun 01; 70(8):899-905. PubMed ID: 20135646.
    Abstract:
    BACKGROUND: The significant association of benign prostatic hyperplasia (BPH) and hypertension indicates a common pathophysiological factor for both diseases. Hyperactivity of the renin-angiotensin system (RAS) has been reported in BPH. Angiotensin II type I (AT1) receptor is the principal mediator of the RAS, and the antagonist, AT1 receptor blocker (ARB), can induce apoptosis in prostate epithelium cells and increase transforming growth factor beta1 (TGF-beta1) expression. We aimed to investigate the mechanism of inhibition of AT1 receptor in prostate epithelium cells and the role of TGF-beta1. METHODS: Human prostate epithelium cell lines were treated with different concentrations of ARB (losartan) (0, 0.1, 1, 10, 100, and 1,000 microM) for 24-72 hr. Cell proliferation was analyzed by cell proliferation assay. The location of AT1 receptor was shown by immunocytohistochemistry and immunocytofluorescence study. Analysis of apoptosis was by use of terminal transferase TdT-mediated dUTP-biotin end labeling (TUNEL) and caspase 3/7 activity assay. Mitochondrial outer-membrane permeabilization was measured by JC-1 staining. The level of TGF-beta1 was determined by enzyme-linked immunosorbent assay. RESULTS: Immunohistochemistry and immunofluorescence analysis showed AT1 receptor expressed in epithelium cells. Compared to control cultures, cultures treated with losartan for 24-72 hr showed a dose-dependent significant decrease in cell number, with apoptosis increased by 65.2%. Decreased cell number was reversed on treatment with anti-TGF-beta1 antibody. TUNEL staining showed increased apoptosis in prostate epithelium cells exposed to losartan. Caspase 3/7 activation was increased and mitochondrial membrane potential was downregulated. Expression of TGF-beta1 in cells treated with losartan was higher than that in untreated cells. CONCLUSIONS: The apoptotic effect of blockade of AT1 receptor on human prostatic epithelium cells may be mediated through an autocrine the production of TGF-beta1. Furthermore, this finding may have implications for medication options. Inc.
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