Brandt Rowena, Krantz Sven
Institute of Medical Biochemistry and Molecular Biology, Ernst Moritz Arndt University, Klinikum Sauerbruchstrasse, D-17487 Greifswald, Germany.
Biochim Biophys Acta. 2006 Nov;1760(11):1749-53. doi: 10.1016/j.bbagen.2006.09.004. Epub 2006 Sep 15.
Increased levels of glycated, Amadori-modified albumin are a risk factor for diabetic vascular disorders. Glycated albumin binds to specific receptors and induces cellular signaling pathways, the complexity of which is largely unknown. Binding of glycated albumin to MonoMac 6 cells leads to an activation of MAPK p44/42 (ERK1/2) and p38 with subsequent translocation of NF-kappaB into the nucleus. The activation of MAPK is in part mediated by protein kinase C activation, but a PKC-independent pathway via MEK-1 is also involved. Protein tyrosine kinases do not play a role in the activation of NF-kappaB. The results may have pathophysiological significance, because the MonoMac 6 cell line is not greatly different from blood monocytes.
糖化、经阿马多里修饰的白蛋白水平升高是糖尿病血管疾病的一个危险因素。糖化白蛋白与特定受体结合并诱导细胞信号通路，其复杂性在很大程度上尚不清楚。糖化白蛋白与单核细胞白血病细胞系MonoMac 6细胞结合会导致丝裂原活化蛋白激酶p44/42（细胞外信号调节激酶1/2，ERK1/2）和p38激活，随后核因子κB（NF-κB）易位至细胞核。丝裂原活化蛋白激酶的激活部分由蛋白激酶C激活介导，但也涉及一条经由丝裂原活化蛋白激酶/细胞外信号调节激酶激酶1（MEK-1）的不依赖蛋白激酶C的途径。蛋白酪氨酸激酶在核因子κB的激活中不起作用。这些结果可能具有病理生理学意义，因为MonoMac 6细胞系与血液单核细胞并无太大差异。
