Calmodulin and calmodulin-dependent protein kinase II inhibit hormone secretion in human parathyroid adenoma

被引:14
作者
Lu, Ming [1 ,2 ,3 ]
Berglund, Erik [1 ]
Larsson, Catharina [1 ,3 ]
Hoog, Anders [4 ]
Farnebo, Lars-Ove [1 ]
Branstrom, Robert [1 ]
机构
[1] Karolinska Inst, Karolinska Univ Hosp L1 03, Dept Mol Med & Surg, SE-17176 Stockholm, Sweden
[2] Guangxi Med Univ, Affiliated Hosp 1, Dept Geriatr Endocrinol, Nanning, Peoples R China
[3] Karolinska Univ Hosp, CMM, SE-17176 Stockholm, Sweden
[4] Karolinska Inst, Karolinska Univ Hosp, Dept Oncol Pathol, SE-17176 Stockholm, Sweden
基金
瑞典研究理事会;
关键词
PANCREATIC BETA-CELLS; CALCIUM INFLUX; CYTOSOLIC CA2+; SYNAPSIN-I; RELEASE; ACTIVATION; INSULIN; PHOSPHORYLATION; CALMIDAZOLIUM; EXOCYTOSIS;
D O I
10.1677/JOE-10-0123
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Intracellular calcium ([Ca2+](i)) is the most relevant modulator of parathyroid hormone (PTH) secretion. Uniquely, an increase in [Ca2+](i) results in an inhibition of PTH secretion, and it probably exerts its function via calcium-binding protein pathways. The ubiquitous calcium-binding proteins, calmodulin and calmodulin-dependent protein kinase II (CaMKII), have well-established roles in regulated exocytosis in neurons and neuroendocrine cells. However, their roles in parathyroid cells and PTH secretion are still unclear. Using reverse transcription-PCR and western blot analysis, we have demonstrated the expression of calmodulin and CaMKII in human normal parathyroid and parathyroid chief cell adenomas. Blocking of calmodulin and CaMKII activity by the specific antagonists calmidazolium and KN-62 respectively caused a rise in PTH secretion from parathyroid adenoma cells in spite of increased [Ca2+](i). The inhibitory effect of Ca2+ calmodulin on PTH secretion may be due to the absence of synaptotagmin 1 protein in parathyroid adenomas, as demonstrated by western blot analysis. An increased extracellular calcium level acutely lowered the amount of active phosphorylated CaMKII (pCaMKII) in adenoma cells in vitro, indicating the physiological importance of this pathway. Moreover, a negative correlation between the levels of pCaMKII in parathyroid adenomas and serum calcium was found in 20 patients with primary hyperparathyroidism. Taken together, these results show that calmodulin negatively contributes to the regulation of PTH secretion in parathyroid adenoma, at least partially via a CaMKII pathway. Journal of Endocrinology (2011) 208, 31-39
引用
收藏
页码:31 / 39
页数:9
相关论文
共 50 条
  • [41] Calcium/calmodulin-dependent protein kinase II contributes to activity-dependent filopodia growth and spine formation
    Jourdain, P
    Fukunaga, K
    Muller, D
    JOURNAL OF NEUROSCIENCE, 2003, 23 (33) : 10645 - 10649
  • [42] Activation State-Dependent Substrate Gating in Ca2+/Calmodulin-Dependent Protein Kinase II
    Johnson, D. E.
    Hudmon, A.
    NEURAL PLASTICITY, 2017, 2017
  • [43] Ca2+/Calmodulin-dependent Protein Kinase Kinase β Is Regulated by Multisite Phosphorylation
    Green, Michelle F.
    Scott, John W.
    Steel, Rohan
    Oakhill, Jonathan S.
    Kemp, Bruce E.
    Means, Anthony R.
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286 (32) : 28066 - 28079
  • [44] Involvement of calcium/calmodulin-dependent protein kinase kinase in meiotic maturation of pig oocytes
    Xu, Bao-Zeng
    Li, Mo
    Xiong, Bo
    Lin, Sheng-Li
    Zhu, Jia-Qiao
    Hou, Yi
    Chen, Da-Yuan
    Sun, Qing-Yuan
    ANIMAL REPRODUCTION SCIENCE, 2009, 111 (01) : 17 - 30
  • [45] Resveratrol Inhibits Neuronal Apoptosis and Elevated Ca2+/Calmodulin-Dependent Protein Kinase II Activity in Diabetic Mouse Retina
    Kim, Young-Hee
    Kim, Yoon-Sook
    Kang, Sang-Soo
    Cho, Gyeong-Jae
    Choi, Wan-Sung
    DIABETES, 2010, 59 (07) : 1825 - 1835
  • [46] Regulation of Ca2+/calmodulin-dependent protein kinase kinase β by cAMP signaling
    Takahatake, Shota
    Ohtsuka, Satomi
    Sugawara, Takeyuki
    Hatano, Naoya
    Kanayama, Naoki
    Magari, Masaki
    Sakagami, Hiroyuki
    Tokumitsu, Hiroshi
    BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2019, 1863 (04): : 672 - 680
  • [47] Investigation of protein substrates of Ca2+/calmodulin-dependent protein kinase II translocated to the postsynaptic density
    Yoshimura, Y
    Aoi, C
    Yamauchi, T
    MOLECULAR BRAIN RESEARCH, 2000, 81 (1-2): : 118 - 128
  • [48] Calmodulin-dependent kinase II regulates osteoblast differentiation through regulation of Osterix
    Choi, You Hee
    Choi, Jun-Ha
    Oh, Jae-Wook
    Lee, Kwang-Youl
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2013, 432 (02) : 248 - 255
  • [49] Alternative splicing of Drosophila calcium/calmodulin-dependent protein kinase II regulates substrate specificity and activation
    GuptaRoy, B
    Marwaha, N
    Pla, M
    Wang, Z
    Nelson, HB
    Beckingham, K
    Griffith, LC
    MOLECULAR BRAIN RESEARCH, 2000, 80 (01): : 26 - 34
  • [50] Phosphorylation and Feedback Regulation of Metabotropic Glutamate Receptor 1 by Calcium/Calmodulin-Dependent Protein Kinase II
    Jin, Dao-Zhong
    Guo, Ming-Lei
    Xue, Bing
    Fibuch, Eugene E.
    Choe, Eun Sang
    Mao, Li-Min
    Wang, John Q.
    JOURNAL OF NEUROSCIENCE, 2013, 33 (08) : 3402 - 3412