Aspirin-induced抑制脂肪生成的磷酸戊糖途径的p - 53依赖的和与失活有关。
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苏YF,杨SH,李YH,公元前吴,黄SC,刘厘米,陈SL,潘YF,周党卫军,瞅我,杨HW
Aspirin-induced抑制脂肪生成的磷酸戊糖途径的p - 53依赖的和与失活有关。
欧元J杂志。2014年9月5日,738:101-10。doi: 10.1016 / j.ejphar.2014.03.009。Epub 2014年4月12日。
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24726874 (在PubMed]
- 文摘
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肥胖已经成为全球的一个主要公共卫生问题的意义。今天,阿司匹林仍然是最常用的药物用于治疗发热、疼痛、炎症和抗血小板。本研究的目的是评估可能存在的一个假定的脂肪形成的p - 53依赖的途径基本aspirin-induced抑制。细胞迁移试验是通过Transwell插入被迁移的能力。油红O染色法来量化脂肪堆积。血糖和甘油三酯的浓度测量使用分析工具。几个主监管分子的表达水平控制各种信号通路被监控使用免疫印迹技术。阿司匹林显著抑制preadipocyte迁移和脂肪堆积。p53-p21信号和分化标记glycerol-3-phosphate脱氢酶的表达增加剂量依赖性的方式。它通过p53-p21表明阿司匹林诱导脂肪细胞的分化途径。 The oncogenic ERK 1/2 MAPK signaling was induced, whereas, the expression of adipogenic markers peroxisome proliferator-activated receptor gamma (PPARgamma), adipocyte fatty acid-binding protein (A-FABP) and inflammatory factors cyclooxygenase-2 (Cox-2), tumor necrosis factor alpha (TNFalpha) and inducible nitric oxide synthase (iNOS) were inhibited. Aspirin negatively regulated the pentose phosphate pathway (PPP) by inhibiting the expression of rate-limiting enzyme glucose-6-phosphate dehydrogenase. Knockdown the expression of oncogenic ERK 1/2 MAPK by using 10 muM PD98059 significantly increased triglyceride synthesis, adipose accumulation and activated PPP, however, decreased glucose uptake. Diverted the glucose flux to PPP, rather than increased glucose uptake, was associated with adipogenesis. Down-regulated the expression of tumor suppressor p53 by 10 muM pifithrin-alpha (PFTalpha) alone had no effect on adipose accumulation. However, administration of aspirin accompanied with PFTalpha abolished aspirin-induced inhibition of adipogenesis. We demonstrated that aspirin-induced inhibition of adipogenesis was p53-dependent and associated with inactivation of PPP. Blockade PPP may be a novel strategy for obesity prevention and therapy. Moreover, when use aspirin in therapeutic strategy, the p53 status should be considered.