Laboratório de Lípides (LIM 10), Hospital das Clínicas (HCFMUSP), Faculdade de Medicina da Universidade de São Paulo, São Paulo CEP 01246-000, Brazil.
Programa de Pós-Graduação em Ciências do Envelhecimento, Universidade São Judas Tadeu, São Paulo CEP 03166-000, Brazil.
Int J Mol Sci. 2020 Oct 1;21(19):7265. doi: 10.3390/ijms21197265.
We addressed the involvement of the receptor for advanced glycation end products (RAGE) in the impairment of the cellular cholesterol efflux elicited by glycated albumin. Albumin was isolated from type 1 (DM1) and type 2 (DM2) diabetes mellitus (HbA1c > 9%) and non-DM subjects (C). Moreover, albumin was glycated in vitro (AGE-albumin). Macrophages from null and wild-type (WT) mice, or THP-1 transfected with siRNA- were treated with C, DM1, DM2, non-glycated or AGE-albumin. The cholesterol efflux was reduced in WT cells exposed to DM1 or DM2 albumin as compared to C, and the intracellular lipid content was increased. These events were not observed in null cells, in which the cholesterol efflux and lipid staining were, respectively, higher and lower when compared to WT cells. In WT, , and mRNA increased and and diminished after treatment with DM1 and DM2 albumin. In null cells treated with DM-albumin, , and were reduced and and increased. In -silenced THP-1, and mRNA were reduced and and were increased even after treatment with AGE or DM-albumin. RAGE mediates the deleterious effects of AGE-albumin in macrophage cholesterol efflux.
我们探讨了晚期糖基化终产物受体（RAGE）在糖化白蛋白引起的细胞胆固醇外排受损中的作用。从 1 型（DM1）和 2 型（DM2）糖尿病（HbA1c>9%）和非 DM 患者（C）中分离出白蛋白。此外，白蛋白在体外发生糖化（AGE-白蛋白）。用 C、DM1、DM2、非糖化或 AGE-白蛋白处理 和 WT 小鼠的巨噬细胞或用 siRNA 转染的 THP-1。与 C 相比，暴露于 DM1 或 DM2 白蛋白的 WT 细胞中的胆固醇外排减少，细胞内脂质含量增加。这些事件在 缺失细胞中未观察到，与 WT 细胞相比， 缺失细胞中的胆固醇外排和脂质染色分别更高和更低。在 WT 中， 、 和 在用 DM1 和 DM2 白蛋白处理后增加， 和 减少。在用 DM-白蛋白处理的 缺失细胞中， 、 和 减少， 和 增加。在沉默的 THP-1 中，即使在用 AGE 或 DM-白蛋白处理后， 和 的 mRNA 减少， 和 的增加。RAGE 介导 AGE-白蛋白对巨噬细胞胆固醇外排的有害作用。
