Wolf G, Neilson E G, Goldfarb S, Ziyadeh F N
Department of Medicine, University of Pennsylvania, Philadelphia 19104.
Biochem Biophys Res Commun. 1991 Apr 30;176(2):902-9. doi: 10.1016/s0006-291x(05)80271-2.
Incubation of cultured murine proximal tubular cells in serum-free media containing 450 mg/dl of glucose resulted in cellular hypertrophy as defined by an increase in cell size, total protein content, and synthesis after 72 h. 10 nM angiotensin II further increased this hypertrophy, but failed to have any effect on cells grown in 100 mg/dl glucose. This enhancement by angiotensin II was blocked by treatment with 1 microM of the angiotensin-receptor antagonist DuP 753. Although cells incubated in either glucose media exhibited similar high-affinity angiotensin II-receptors, the receptor density was elevated only in cells grown in the presence of high glucose. Stimulation of cells in high glucose for 60 min with 10 nM angiotensin II also reduced significantly intracellular cAMP concentrations. This was not the case for proximal tubular cells cultured in normal glucose. Our results indicate that high glucose and angiotensin II have additive effects on the induction of hypertrophy in renal tubular cells.
将培养的小鼠近端肾小管细胞置于含有450mg/dl葡萄糖的无血清培养基中孵育72小时后，细胞出现肥大，表现为细胞大小增加、总蛋白含量增加以及合成增加。10nM血管紧张素II进一步加剧了这种肥大，但对在100mg/dl葡萄糖中生长的细胞没有任何影响。血管紧张素II的这种增强作用可被1μM血管紧张素受体拮抗剂DuP 753阻断。尽管在任一种葡萄糖培养基中孵育的细胞都表现出相似的高亲和力血管紧张素II受体，但仅在高糖环境下生长的细胞中受体密度升高。用10nM血管紧张素II刺激高糖环境中的细胞60分钟，也会显著降低细胞内cAMP浓度。而在正常葡萄糖环境中培养的近端肾小管细胞则不会出现这种情况。我们的结果表明，高糖和血管紧张素II对肾小管细胞肥大的诱导具有相加作用。
