tailieunhanh - Báo cáo hóa học: " Prevention of hyperglycemia-induced myocardial apoptosis by gene silencing of Toll-like receptor-4"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Prevention of hyperglycemia-induced myocardial apoptosis by gene silencing of Toll-like receptor-4 | Zhang et al. Journal of Translational Medicine 2010 8 133 http content 8 1 133 TRANSLATIONAL MEDICINE RESEARCH Open Access Prevention of hyperglycemia-induced myocardial apoptosis by gene silencing of Toll-like receptor-4 Yuwei Zhang1 Tianqing Peng2 3 Huaqing Zhu2 Xiufen Zheng2 Xusheng Zhang2 Nan Jiang2 Xiaoshu Cheng4 V I z tin I I4 A -s chi I 1 I z2 h I IZX z-xt- Civs z i 2 l I o I I D I r r 5 f I rzx I V o r z t 1 6 ì I n A r si I z t 1 Xiaoyan Lai Aminah Shunnar Manpreet Singh Neil Riordan Vladimir Bogin Nanwei long Wei-Ping Min2 3 4 Abstract Background Apoptosis is an early event involved in cardiomyopathy associated with diabetes mellitus. Toll-like receptor TLR signaling triggers cell apoptosis through multiple mechanisms. Up-regulation of TLR4 expression has been shown in diabetic mice. This study aimed to delineate the role of TLR4 in myocardial apoptosis and to block this process through gene silencing of TLR4 in the myocardia of diabetic mice. Methods Diabetes was induced in C57 BL6 mice by the injection of streptozotocin. Diabetic mice were treated with 50 pg of TLR4 siRNA or scrambled siRNA as control. Myocardial apoptosis was determined by TUNEL assay. Results After 7 days of hyperglycemia the level of TLR4 mRNA in myocardial tissue was significantly elevated. Treatment of TLR4 siRNA knocked down gene expression as well as diminished its elevation in diabetic mice. Apoptosis was evident in cardiac tissues of diabetic mice as detected by a TUNEL assay. In contrast treatment with TLR4 siRNA minimized apoptosis in myocardial tissues. Mechanistically caspase-3 activation was significantly inhibited in mice that were treated with TLR4 siRNA but not in mice treated with control siRNA. Additionally gene silencing of TLR4 resulted in suppression of apoptotic cascades such as Fas and caspase-3 gene expression. TLR4 deficiency resulted in inhibition of reactive oxygen species ROS production and NADPH oxidase activity suggesting .

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