Vaena de Avalos S, Lima C, Martini C, de Lederkremer R M, Vila M C
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Steroids. 1998 Feb;63(2):70-5. doi: 10.1016/s0039-128x(97)00137-2.
In the present paper, we report that an inositolphosphoglycan (IPG), derived from a Trypanosoma cruzi glycoinositolphosphoceramide (LPPG), is able to inhibit ACTH-mediated accumulation of a glucocorticoid, cortisol, in calf adrenocortical cells. This IPG is also able to inhibit the stimulation by ACTH of the production of the main glucocorticoid, corticosterone and the main mineralocorticoid, aldosterone, in rat adrenocortical cells. Nitrous acid deamination confirmed that IPG is responsible for this inhibition. In order to study the involvement of glycosylphosphatidylinositol (GPI) in ACTH response in rat adrenal cortex, the activation of a phospholipase that hydrolyzes GPI (GPI-PLC) was evaluated. It was found that the release of alkaline phosphatase, a GPI-anchored enzyme, to the extracellular medium is increased in rat adrenocortical cells by ACTH treatment. In addition, ACTH stimulates the release of ceramide from the glycoinositolphosphoceramide purified from T. cruzi. These data suggest that ACTH activates a GPI-PLC in rat adrenal cortex, which is in agreement with our previous data in calf adrenocortical cells; thus, the hydrolysis of GPI provoked by ACTH takes place in different mammals and the IPG released could inhibit ACTH-mediated synthesis of aldosterone, corticosterone and cortisol.
在本论文中,我们报告称,一种源自克氏锥虫糖肌醇磷酸神经酰胺(LPPG)的肌醇磷酸聚糖(IPG)能够抑制促肾上腺皮质激素(ACTH)介导的小牛肾上腺皮质细胞中糖皮质激素皮质醇的积累。这种IPG还能够抑制促肾上腺皮质激素对大鼠肾上腺皮质细胞中主要糖皮质激素皮质酮以及主要盐皮质激素醛固酮产生的刺激作用。亚硝酸脱氨基作用证实了IPG是这种抑制作用的原因。为了研究糖基磷脂酰肌醇(GPI)在大鼠肾上腺皮质对促肾上腺皮质激素反应中的作用,对一种水解GPI的磷脂酶(GPI-PLC)的激活情况进行了评估。结果发现,经促肾上腺皮质激素处理后,大鼠肾上腺皮质细胞中一种GPI锚定酶碱性磷酸酶释放到细胞外培养基中的量增加。此外,促肾上腺皮质激素刺激从克氏锥虫纯化得到的糖肌醇磷酸神经酰胺释放神经酰胺。这些数据表明,促肾上腺皮质激素激活了大鼠肾上腺皮质中的GPI-PLC,这与我们之前在小牛肾上腺皮质细胞中的数据一致;因此,促肾上腺皮质激素引发的GPI水解在不同哺乳动物中都会发生,释放出的IPG能够抑制促肾上腺皮质激素介导的醛固酮、皮质酮和皮质醇的合成。