Department of Biological Sciences, Faculty of Science and Engineering, The University of Waikato, Private Bag 3105, Hamilton, New Zealand.
Cell Stress Chaperones. 2012 Jan;17(1):23-8. doi: 10.1007/s12192-011-0282-6. Epub 2011 Jul 16.
Metformin is in widespread clinical use for the treatment of diabetes mellitus in patients. It has been shown to inhibit mitochondrial bioenergetic functions by inhibiting complex I of the electron transport chain. The expression of mitochondrial-specific molecular stress protein Hsp60 is a key consequence of mitochondrial impairment. Since this protein has important immune-modulatory properties, we have investigated the expression of Hsp60 in human THP-1 monocyte cells exposed to metformin. In this study, we demonstrate significant up-regulation of Hsp60 at both mRNA and protein levels when these cells were exposed to metformin at therapeutic dosage levels. Interestingly, there was also an increase in expression of CD14 mRNA in these cells. This suggested a possible modulation of the differentiation rates of the THP-1 cells during exposure to metformin. As monocyte differentiation marks a critical step in atherosclerosis, these observations suggest that long-term exposure to metformin could have important implications for the diabetic patient.
二甲双胍在临床上广泛用于治疗糖尿病患者。它已被证明通过抑制电子传递链的复合物 I 来抑制线粒体生物能功能。线粒体特异性分子应激蛋白 Hsp60 的表达是线粒体损伤的关键后果。由于这种蛋白质具有重要的免疫调节特性，我们研究了暴露于二甲双胍的人 THP-1 单核细胞中 Hsp60 的表达。在这项研究中，当这些细胞暴露于治疗剂量的二甲双胍时，我们在 mRNA 和蛋白质水平上都证明了 Hsp60 的显著上调。有趣的是，这些细胞中的 CD14 mRNA 的表达也增加了。这表明在暴露于二甲双胍期间，THP-1 细胞的分化率可能发生了变化。由于单核细胞分化标志着动脉粥样硬化的一个关键步骤，这些观察结果表明，长期暴露于二甲双胍可能对糖尿病患者有重要影响。
