Jindrichová S, Nováková O, Bryndová J, Tvrzická E, Lisá V, Novák F, Pácha J
Institute of Physiology, Czech Academy of Sciences, Vídenská 1083, 142 20 Prague 4-Krc, Czech Republic.
J Steroid Biochem Mol Biol. 2003 Nov;87(2-3):157-65. doi: 10.1016/j.jsbmb.2003.08.005.
Previous studies from our laboratory have indicated that secondary hyperaldosteronism affects phospholipids of rat colonic enterocytes. To assess whether this represents a direct effect of mineralocorticoids on enterocytes, the role of aldosterone and dexamethasone in the regulation of lipid metabolism was examined in Caco-2 cells during development of their enterocyte phenotype. Differentiation of Caco-2 cells was associated with increased levels of triglycerides (TG) and cholesteryl esters (CE), a decreased content of cholesterol and phospholipids and changes in individual phospholipid classes. The phospholipids of differentiated cells had a higher content of n-6 polyunsaturated fatty acids (PUFA) and lower amounts of monounsaturated (MUFA) and saturated fatty acids than subconfluent undifferentiated cells. Differentiated cells exhibited a higher ability to incorporate [3H]arachidonic acid (AA) into cellular phospholipids and a lower ability for incorporation into TG and CE. Incubation of subconfluent undifferentiated cells with aldosterone or dexamethasone was without effect on the content of lipids, their fatty acids and [3H]AA incorporation. In contrast, aldosterone treatment of differentiated cells diminished the content of TG, increased the content of phospholipids and modulated their fatty acid composition. The percentage of n-6 and n-3 PUFA in phospholipids was increased and that of MUFA decreased, whereas no changes in TG were observed. The incorporation of [3H]AA into phospholipids was increased and into TG decreased and these changes were blocked by spironolactone. Treatment of differentiated cells with dexamethasone increased their CE content but no effect was identified upon other lipids, their fatty acid composition and on the incorporation of [3H]AA. As expected for the involvement of corticosteroid hormones the mineralocorticoid and glucocorticoid receptors were identified in Caco-2 cells by RT-PCR. The results suggest that aldosterone had a profound influence on lipid metabolism in enterocytes and that its effect depends on the stage of differentiation. The aldosterone-dependent changes occurring in phospholipids and their fatty acid composition may reflect a physiologically important phenomenon with long-term consequences for membrane structure and function.
我们实验室之前的研究表明，继发性醛固酮增多症会影响大鼠结肠肠上皮细胞的磷脂。为了评估这是否代表盐皮质激素对肠上皮细胞的直接作用，在Caco-2细胞肠上皮细胞表型发育过程中，研究了醛固酮和地塞米松在脂质代谢调节中的作用。Caco-2细胞的分化与甘油三酯（TG）和胆固醇酯（CE）水平升高、胆固醇和磷脂含量降低以及个别磷脂类别的变化有关。与未汇合的未分化细胞相比，分化细胞的磷脂中n-6多不饱和脂肪酸（PUFA）含量更高，单不饱和脂肪酸（MUFA）和饱和脂肪酸含量更低。分化细胞将[3H]花生四烯酸（AA）掺入细胞磷脂的能力更高，而掺入TG和CE的能力更低。用醛固酮或地塞米松孵育未汇合的未分化细胞对脂质含量、其脂肪酸以及[3H]AA掺入没有影响。相反，用醛固酮处理分化细胞会降低TG含量，增加磷脂含量并调节其脂肪酸组成。磷脂中n-6和n-3 PUFA的百分比增加，MUFA的百分比降低，而TG未观察到变化。[3H]AA掺入磷脂增加，掺入TG减少，这些变化被螺内酯阻断。用地塞米松处理分化细胞会增加其CE含量，但对其他脂质、其脂肪酸组成以及[3H]AA掺入没有影响。正如预期的那样，通过RT-PCR在Caco-2细胞中鉴定出盐皮质激素和糖皮质激素受体。结果表明，醛固酮对肠上皮细胞的脂质代谢有深远影响，其作用取决于分化阶段。磷脂及其脂肪酸组成中发生的醛固酮依赖性变化可能反映了一种具有重要生理意义的现象，对膜结构和功能有长期影响。
