Wang Dong, Wei Yuren, Frye Melinda, Gentile Christopher L, Pagliassotti Michael J
Department of Food Science and Human Nutrition, Colorado State University, 234 Gifford, Fort Collins, CO 80523-1571, USA.
J Nutr Metab. 2013;2013:514206. doi: 10.1155/2013/514206. Epub 2013 Apr 15.
Liver specific deletion of the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) induces steatosis and hypersensitivity to insulin. Saturated fatty acids, which induce endoplasmic reticulum stress and cell death, appear to increase PTEN, whereas unsaturated fatty acids which do not induce endoplasmic reticulum stress or cell death reduce this protein. In the present study, the role of PTEN in saturated fatty acid-induced cytotoxicity was examined in H4IIE and HepG2 liver cells. Palmitate and stearate increased the expression of PTEN, whereas the unsaturated fatty acids, oleate and linoleate, reduced PTEN expression in both cell types. SiRNA-mediated knockdown of PTEN did not increase liver cell triglyceride stores or reduce palmitate- or stearate-mediated ER stress or apoptosis. These results suggest that PTEN does not play a significant role in saturated fatty acid-induced cytotoxicity in these liver cell models and in the absence of insulin.
肝脏特异性缺失10号染色体上缺失的肿瘤抑制磷酸酶和张力蛋白同源物（PTEN）会诱发脂肪变性和对胰岛素的超敏反应。诱导内质网应激和细胞死亡的饱和脂肪酸似乎会增加PTEN，而不诱导内质网应激或细胞死亡的不饱和脂肪酸则会降低这种蛋白质的水平。在本研究中，在H4IIE和HepG2肝细胞中检测了PTEN在饱和脂肪酸诱导的细胞毒性中的作用。棕榈酸酯和硬脂酸酯增加了PTEN的表达，而不饱和脂肪酸油酸酯和亚油酸酯则降低了这两种细胞类型中PTEN的表达。RNA干扰介导的PTEN敲低并没有增加肝细胞甘油三酯的储存，也没有降低棕榈酸酯或硬脂酸酯介导的内质网应激或细胞凋亡。这些结果表明，在这些肝细胞模型中以及在没有胰岛素的情况下，PTEN在饱和脂肪酸诱导的细胞毒性中不发挥重要作用。
