Hexose-6-phosphate dehydrogenase and 11β-hydroxysteroid dehydrogenase-1 tissue distribution in the rat
Hexose-6-phosphate dehydrogenase and 11β-hydroxysteroid dehydrogenase-1 tissue distribution in the rat
复制标题
DOI：
10.1210/en.2007-0328
复制
发表时间：
2008-02-01
期刊：
影响因子：
4.8
通讯作者：
Gomez-Sanchez, Celso E.
中科院分区：
文献类型：
--
作者：
Gomez-Sanchez, Elise P.;Romero, Damian G.;Gomez-Sanchez, Celso E.
细胞内糖皮质激素皮质醇和皮质酮的浓度由酶11 β -羟基类固醇脱氢酶（11 β - hsd） 1和2.11 β - hsd1是一种还原的烟酰胺腺嘌呤二核苷酸磷酸（NADPH）依赖的微粒体还原酶调节，该酶将无活性的糖皮质激素可的松和11-脱氢皮质酮- 1转化为活性形式皮质醇和皮质酮。己糖-6-磷酸脱氢酶（H6PDH）是一种由内质网内氧化的NADP（NADP(+)）产生NADPH的酶。在缺乏NADPH或H6PDH再生NADPH的情况下，11 - β - hsd1作为脱氢酶并使糖皮质激素失活，11 - β - hsd2也是如此。制备了一种抗H6PDH的单克隆抗体，以研究在缺乏H6PDH的情况下，11 β - hsd1可能对不表达大量11 β - hsd2的组织中的羟基类固醇脱氢酶活性负责。采用实时RT-PCR、Western blot和免疫组化检测H6PDH和11 β - hsd1在大鼠多种组织中的表达情况。H6PDH存在于多种组织中，在肝、肾和间质细胞中浓度最高。虽然整个大脑没有表达大量的H6PDH，但通过免疫组化，一些神经元明显具有免疫反应性。H6PDH在大多数组织中充分表达，其中11 β -HSD1也表达，但肾间质细胞明显例外，其中11 β -HSD1的脱氢酶活性可能会调节糖皮质激素受体的激活，因为大鼠肾间质细胞没有大量的矿皮质激素受体。这种抗H6PDH的抗体将有助于进一步研究内质网内生成NADPH所需的酶活性。
Intracellular concentrations of the glucocorticoids cortisol and corticosterone are modulated by the enzymes 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) 1 and 2.11 beta-HSD1 is a reduced nicotinamide adenine dinucleotide phosphate ( NADPH)-dependent microsomal reductase that converts the inactive glucocorticoids cortisone and 11-dehydrocorticoster-one to their active forms, cortisol and corticosterone. Hexose-6-phosphate dehydrogenase (H6PDH) is an enzyme that generates NADPH from oxidized NADP (NADP(+)) within the endoplasmic reticulum. In the absence of NADPH or H6PDH to regenerate NADPH, 11 beta-HSD1 acts as a dehydrogenase and inactivates glucocorticoids, as does 11 beta-HSD2. A monoclonal antibody against H6PDH was produced to study the possibility that 11 beta-HSD1 in the absence of H6PDH may be responsible for hydroxysteroid dehydrogenase activity in tissues that do not express significant amounts of 11 beta-HSD2. H6PDH and 11 beta-HSD1 expression was surveyed in a variety of rat tissues by real-time RT-PCR, Western blot analysis, and immunohistochemistry. H6PDH was found in a wide variety of tissues, with the greatest concentrations in the liver, kidney, and Leydig cells. Although the brain as a whole did not express significant amounts of H6PDH, some neurons were clearly immunoreactive by immunohistochemistry. H6PDH was amply expressed in most tissues examined in which 11 beta-HSD1 was also expressed, with the notable exception of the renal interstitial cells, in which dehydrogenase activity by 11 beta HSD1 probably moderates activation of the glucocorticoid receptor because rat renal interstitial cells do not have significant amounts of mineralocorticoid receptors. This antibody against the H6PDH should prove useful for further studies of enzyme activity requiring NADPH generation within the endoplasmic reticulum.