Department of Nephrology, Provincial Hospital Affiliated to Shandong University, JiNan, China.
Ren Fail. 2012;34(5):616-21. doi: 10.3109/0886022X.2012.668491. Epub 2012 Mar 27.
Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is known as a mammalian cell energy sensor, which could regulate cellular energy metabolism via sensing the alterations of energy balance, such as oversupply or lack of glucose and fatty acid. Recent studies have suggested that AMPK could also regulate many other biological processes, including cell cycling, inflammation, protein synthesis, and so on. In this study, AMPK signaling in high-glucose-induced dysfunction of mesangial cells (MCs) was investigated.
Established rat glomerular MCs were treated under normal glucose (5.6 mM glucose) or high-glucose conditions (30 mM glucose). mRNA levels of AMPK subunits were detected by reverse transcriptase-polymerase chain reaction. Expressions of AMPKα, phosphorylated AMPKα (p-AMPKα), phosphorylated acetyl-CoA carboxylase (p-ACC), and collagen IV were measured by Western blot.
Under high-glucose conditions, AMPKα protein expression and mRNA levels were significantly decreased. High-glucose treatment also induced a notable decrease in p-AMPKα and p-ACC expression. AMPKα activation by 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) effectively ameliorated high-glucose-induced dysfunction of MCs, including cell proliferation, cell-cycle progression, and collagen IV production.
High glucose impaired AMPKα in its expression and activity; AICAR significantly ameliorated high-glucose-induced proliferation of MCs and collagen IV production, indicating a role of AMPKα in high-glucose-induced dysfunction of MCs.
腺苷 5'-单磷酸（AMP）激活的蛋白激酶（AMPK）被认为是哺乳动物细胞的能量传感器，通过感知能量平衡的改变，如葡萄糖和脂肪酸的供应过多或缺乏，来调节细胞能量代谢。最近的研究表明，AMPK 还可以调节许多其他生物过程，包括细胞周期、炎症、蛋白质合成等。本研究旨在探讨 AMPK 信号在高糖诱导的肾小球系膜细胞（MCs）功能障碍中的作用。
用正常葡萄糖（5.6mM 葡萄糖）或高葡萄糖（30mM 葡萄糖）处理建立的大鼠肾小球系膜细胞。逆转录-聚合酶链反应检测 AMPK 亚基的 mRNA 水平。用 Western blot 检测 AMPKα、磷酸化 AMPKα（p-AMPKα）、磷酸化乙酰辅酶 A 羧化酶（p-ACC）和胶原 IV 的表达。
在高葡萄糖条件下，AMPKα 蛋白表达和 mRNA 水平显著降低。高葡萄糖处理也显著诱导 p-AMPKα 和 p-ACC 表达降低。5-氨基咪唑-4-甲酰胺-1-β-D-核糖呋喃糖苷（AICAR）激活 AMPKα 可有效改善高葡萄糖诱导的 MCs 功能障碍，包括细胞增殖、细胞周期进程和胶原 IV 产生。
高葡萄糖损害了 AMPKα 的表达和活性；AICAR 显著改善了高葡萄糖诱导的 MCs 增殖和胶原 IV 产生，表明 AMPKα 在高葡萄糖诱导的 MCs 功能障碍中发挥作用。
