Braas K M, Harakall S A, Ouafik L, Eipper B A, May V
Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington 05405.
Endocrinology. 1992 May;130(5):2778-88. doi: 10.1210/endo.130.5.1572293.
Peptide alpha-amidation, an essential posttranslational modification that confers bioactivity to many neuroendocrine peptides, is catalyzed by peptidylglycine alpha-amidating monooxygenase (PAM; EC 1.14.17.3). To complement our previous studies on the distribution of PAM in neuroendocrine organs, we have examined expression of the PAM gene in several endocrine tissues by in situ hybridization and immunocytochemistry. In all instances, the autoradiographic densities for PAM mRNA correlated with staining patterns for PAM immunoreactivity. Very high levels of PAM mRNA were found in all heart atrial cardiomyocytes, while much lower levels were present in ventricular cells. In the sublingual gland, PAM was expressed diffusely in both acinar and tubule cells. In contrast, expression of PAM was confined to granular convoluted tubule cells in the submaxillary gland. PAM was expressed at high levels in a subset of adrenal medullary chromaffin cells, and low levels of PAM mRNA and immunoreactivity were also detected in the adrenal cortex. PAM was found predominantly in the calcitonin-producing parafollicular C-cells in the thyroid gland and in the glucagon-containing A-cells in the endocrine pancreas. Collecting and distal tubule cells of the kidney expressed both PAM mRNA and immunoreactivity. The basal cells in testicular seminiferous tubules containing PAM may represent developing germ and Sertoli cells. The cellular localization of PAM within the thyroid gland, adrenal gland, testis, and pancreas correlated with known peptidergic systems, and some of the observed cellular heterogeneity in PAM mRNA expression and immunoreactivity may reflect differences in the levels of amidated peptide production. The expression of PAM in cells not known to produce high levels of alpha-amidated peptides may indicate the production of yet unidentified alpha-amidated bioactive peptides or alternative functions of the PAM protein.
肽α-酰胺化是一种重要的翻译后修饰，赋予许多神经内分泌肽生物活性，由肽基甘氨酸α-酰胺化单加氧酶（PAM；EC 1.14.17.3）催化。为补充我们之前关于PAM在神经内分泌器官中分布的研究，我们通过原位杂交和免疫细胞化学检测了PAM基因在几种内分泌组织中的表达。在所有情况下，PAM mRNA的放射自显影密度与PAM免疫反应性的染色模式相关。在所有心房心肌细胞中发现了非常高水平的PAM mRNA，而心室细胞中的水平则低得多。在舌下腺中，PAM在腺泡细胞和小管细胞中均有弥散性表达。相反，PAM的表达局限于颌下腺的颗粒曲管细胞。PAM在肾上腺髓质嗜铬细胞的一个亚群中高水平表达，在肾上腺皮质中也检测到低水平的PAM mRNA和免疫反应性。PAM主要存在于甲状腺中产生降钙素的滤泡旁C细胞和内分泌胰腺中含胰高血糖素的A细胞中。肾集合管和远曲小管细胞表达PAM mRNA和免疫反应性。睾丸生精小管中含有PAM的基底细胞可能代表发育中的生殖细胞和支持细胞。PAM在甲状腺、肾上腺、睾丸和胰腺内的细胞定位与已知的肽能系统相关，并且在PAM mRNA表达和免疫反应性中观察到的一些细胞异质性可能反映了酰胺化肽产生水平的差异。PAM在未知产生高水平α-酰胺化肽的细胞中的表达可能表明产生了尚未鉴定的α-酰胺化生物活性肽或PAM蛋白的其他功能。
