Lu Ming, Forsberg Lars, Höög Anders, Juhlin Christofer C, Vukojević Vladana, Larsson Catharina, Conigrave Arthur D, Delbridge Leigh W, Gill Anthony, Bark Christina, Farnebo Lars-Ove, Bränström Robert
Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Mol Cell Endocrinol. 2008 Jun 11;287(1-2):72-80. doi: 10.1016/j.mce.2008.01.028. Epub 2008 Mar 10.
In regulated exocytosis synaptosomal-associated protein of 25kDa (SNAP-25) is one of the key-players in the formation of SNARE (soluble N-ethylmaleimide-sensitive fusion attachment protein receptor) complex and membrane fusion. SNARE proteins are essentially expressed in neurons, neuroendocrine and endocrine cells. Whether parathyroid cells express these proteins is not known. In this study, we have examined the expression of the SNARE protein SNAP-25 and its cellular homologue SNAP-23, as well as syntaxin1 and VAMP (vesicle-associated membrane protein) in samples of normal parathyroid tissue, chief cell adenoma, and parathyroid carcinoma, using immunohistochemistry and Western blot analysis. SNAP-23 and VAMP were evenly expressed in all studied parathyroid tissues using immunohistochemistry and/or Western blot analysis. SNAP-25 (and Syntaxin1) was not expressed in normal parathyroid tissue, but in approximately 20% of chief cell adenomas, and in approximately 45% of parathyroid carcinoma samples. It is likely that the SNARE proteins SNAP-23 and VAMP play a role in the stimulus-secretion coupling and exocytosis of parathyroid hormone as these proteins were expressed in all of the parathyroid samples we studied. In particular, preferential expression of SNAP-23 rather than SNAP-25 provides an explanation of the high level of PTH secretion that occurs under conditions of low cytoplasmic free Ca(2+) concentration (around 0.1micromol/l). SNAP-25 (and Syntaxin1) appears to be a tumour-specific protein(s) in parathyroid tissues since its expression was restricted to pathological tissues.
在调节性胞吐作用中,25kDa的突触体相关蛋白(SNAP - 25)是SNARE(可溶性N - 乙基马来酰亚胺敏感融合附着蛋白受体)复合体形成和膜融合的关键参与者之一。SNARE蛋白主要在神经元、神经内分泌和内分泌细胞中表达。甲状旁腺细胞是否表达这些蛋白尚不清楚。在本研究中,我们使用免疫组织化学和蛋白质印迹分析,检测了正常甲状旁腺组织、主细胞腺瘤和甲状旁腺癌样本中SNARE蛋白SNAP - 25及其细胞同源物SNAP - 23,以及 syntaxin1和VAMP(囊泡相关膜蛋白)的表达。使用免疫组织化学和/或蛋白质印迹分析,SNAP - 23和VAMP在所有研究的甲状旁腺组织中均有均匀表达。SNAP - 25(和Syntaxin1)在正常甲状旁腺组织中不表达,但在约20%的主细胞腺瘤和约45%的甲状旁腺癌样本中表达。SNARE蛋白SNAP - 23和VAMP可能在甲状旁腺激素的刺激 - 分泌偶联和胞吐作用中发挥作用,因为这些蛋白在我们研究的所有甲状旁腺样本中均有表达。特别是,SNAP - 23而非SNAP - 25的优先表达解释了在低细胞质游离Ca(2+)浓度(约0.1微摩尔/升)条件下发生的高水平甲状旁腺激素分泌。SNAP - 25(和Syntaxin1)似乎是甲状旁腺组织中的肿瘤特异性蛋白,因为其表达仅限于病理组织。