Bartling Babett, Fuchs Christine, Somoza Veronika, Niemann Bernd, Silber Rolf-Edgar, Simm Andreas
Cardio-thoracic Surgery, Martin Luther University Halle-Wittenberg, Halle/Saale, Germany.
Mol Nutr Food Res. 2007 Apr;51(4):479-87. doi: 10.1002/mnfr.200600223.
High mobility group box protein 1 (HMGB1) is a ubiquitous nuclear protein that can be actively released from the cell in certain conditions thereby mediating cytokine-like function. While nuclear HMGB1 modulates the transcriptional activity of cells, extracellular HMGB1 partially acts via binding to the receptor for advanced glycation end products (RAGE), which is highly expressed in lung tissue. Therefore, we studied the impact of food-derived advanced glycation end products (AGEs), the Maillard reaction products, on the lung expression of HMGB1. Feeding rats with AGE-rich diet, containing either bread crust or coffee beverage, resulted in an upregulation of HMGB1 mRNA and protein especially in those animals receiving bread crust diet. The expression of RAGE was not influenced. Moreover, we revealed a positive correlation between an increased lung AGE level and HMGB1 protein expression in both animal groups receiving either bread crust or coffee extract but not in the control group. In contrast, the ageing-related AGE accumulation was not associated with an increased level of HMGB1 protein in lung tissue from senescent (100 wk) compared to young-adult (24 wk) rats. Our data suggest a physiological role of food- but not ageing-associated AGEs in the regulation of the HMGB1 expression in lung.
高迁移率族蛋白B1（HMGB1）是一种普遍存在的核蛋白，在某些条件下可从细胞中主动释放，从而介导细胞因子样功能。虽然核内HMGB1调节细胞的转录活性，但细胞外HMGB1部分通过与晚期糖基化终末产物受体（RAGE）结合发挥作用，RAGE在肺组织中高表达。因此，我们研究了食物来源的晚期糖基化终末产物（AGEs），即美拉德反应产物，对肺组织中HMGB1表达的影响。用富含AGEs的饮食喂养大鼠，饮食中含有面包皮或咖啡饮料，导致HMGB1 mRNA和蛋白上调，尤其是在那些接受面包皮饮食的动物中。RAGE的表达未受影响。此外，我们发现，在接受面包皮或咖啡提取物的两个动物组中，肺组织中AGE水平升高与HMGB1蛋白表达呈正相关，但在对照组中未发现这种相关性。相比之下，与衰老相关的AGE积累与衰老（100周）大鼠肺组织中HMGB1蛋白水平升高无关，而年轻成年（24周）大鼠肺组织中HMGB1蛋白水平升高。我们的数据表明，食物来源而非衰老相关的AGEs在调节肺组织中HMGB1表达方面具有生理作用。
