Leitersdorf E, Stein O, Stein Y
Biochim Biophys Acta. 1985 Jul 9;835(2):183-90. doi: 10.1016/0005-2760(85)90272-3.
Bovine adrenal cells were isolated from the subcapsular region of the gland to obtain cultures enriched in cells of the zona glomerulosa. The cells kept in primary cultures were shown to respond to angiotensin II and adrenocorticorticotropin (ACTH) by a significant increase in aldosterone production. These primary adrenal cultures were used to study the effect of angiotensin II on LDL metabolism. Addition of angiotensin II for 48 h to the culture medium resulted in a 200-300% increase in LDL metabolism, and the lowest effective concentration was 10(-8) -10(-9) M. The angiotensin II effect became evident after 12-16 h of incubation. To compare the metabolism of the 125I-labeled protein moiety to that of cholesteryl ester of LDL, the lipoprotein was labeled also with cholesteryl linoleyl ether, a nonhydrolyzable analog of cholesteryl ester. Under basal conditions and in the presence of angiotensin II or ACTH the ratio of [3H]cholesteryl linoleyl ether to 125I indicate some preferential uptake of the cholesteryl ester moiety. Stimulation of specific LDL binding at 4 degrees C and LDL metabolism at 37 degrees C by 10(-7) M angiotensin II occurred at all concentrations of LDL studied. Linearization of the kinetic data showed that angiotensin II increased the LDL receptor number significantly but not the affinity of the LDL receptor for its ligand. The present findings indicate that in analogy to ACTH, angiotensin II can influence receptor-mediated uptake of LDL by adrenal cortical cells. It remains to be shown whether the angiotensin II effect on LDL metabolism is limited to adrenal cells or will affect other cells which express the angiotensin II receptor.
从牛肾上腺被膜下区域分离细胞,以获得富含球状带细胞的培养物。原代培养的细胞显示,血管紧张素II和促肾上腺皮质激素(ACTH)可使其醛固酮分泌显著增加。这些原代肾上腺培养物用于研究血管紧张素II对低密度脂蛋白(LDL)代谢的影响。向培养基中添加血管紧张素II 48小时,可使LDL代谢增加200% - 300%,最低有效浓度为10^(-8) - 10^(-9) M。孵育12 - 16小时后,血管紧张素II的作用变得明显。为了比较125I标记的蛋白质部分与LDL胆固醇酯部分的代谢情况,LDL还用胆固醇亚油酸醚进行标记,胆固醇亚油酸醚是胆固醇酯的一种不可水解类似物。在基础条件下以及存在血管紧张素II或ACTH的情况下,[3H]胆固醇亚油酸醚与125I的比值表明胆固醇酯部分有一些优先摄取。在所有研究的LDL浓度下,10^(-7) M血管紧张素II均可刺激4℃时特异性LDL结合以及37℃时LDL代谢。动力学数据的线性化表明,血管紧张素II显著增加了LDL受体数量,但未增加LDL受体对其配体的亲和力。目前的研究结果表明,与ACTH类似,血管紧张素II可影响肾上腺皮质细胞受体介导的LDL摄取。血管紧张素II对LDL代谢的影响是否仅限于肾上腺细胞,还是会影响其他表达血管紧张素II受体的细胞,仍有待确定。