Deletion of the secretory vesicle proteins IA-2 and IA-2β disrupts circadian rhythms of cardiovascular and physical activity
Deletion of the secretory vesicle proteins IA-2 and IA-2β disrupts circadian rhythms of cardiovascular and physical activity
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DOI：
10.1096/fj.09-132019
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发表时间：
2009-09-01
期刊：
影响因子：
4.8
通讯作者：
Notkins, Abner L.
中科院分区：
文献类型：
--
作者：
Kim, Soo Mi;Power, Andrea;Notkins, Abner L.
I型糖尿病的主要自身抗原IA-2和IA-2β和跨膜分泌囊泡蛋白的靶向缺失会导致激素和神经递质的分泌受损。在目前的研究中，我们评估了这些缺失对血压、心率、核心体温以及自发的身体和神经元活动的日常节律的影响。我们发现，IA-2和IA-2β的缺失都会深刻地扰乱这些参数的日常变化，而单独删除IA-2或IA-2β并不会产生重大变化。原位杂交显示，IA-2和IA-2β转录本在视交叉上核高度但非节律地表达，视交叉上核是大脑的主要昼夜节律振荡器的位置。对视交叉上核组织切片的电生理学研究表明，IA-2和IA-2β的干扰都会导致神经元放电的显著变化。从这些研究中，我们得出结论，IA-2和IA-2β的缺失对昼夜节律系统有深远的影响。-Kim，S.M.，Power，A.，Brown，T.M.，Constance，C.M.，Coon，S.L.，Nishimura，T.，Hirai，H.，Cai，T.，Eisner，C.，Weaver，D.R.，Piggins，H.D.，Klein，D.C.，Schnermann，J.，Notkins，分泌囊泡蛋白IA-2和IA-2β的缺失会扰乱心血管和体力活动的昼夜节律。FASE B J.23,3226-3232(2009)。Www.fasebj.org
Targeted deletion of IA-2 and IA-2 beta, major autoantigens in type 1 diabetes and transmembrane secretory vesicle proteins, results in impaired secretion of hormones and neurotransmitters. In the present study, we evaluated the effect of these deletions on daily rhythms in blood pressure, heart rate, core body temperature, and spontaneous physical and neuronal activity. We found that deletion of both IA-2 and IA-2 beta profoundly disrupts the usual diurnal variation of each of these parameters, whereas the deletion of either IA-2 or IA-2 beta alone did not produce a major change. In situ hybridization revealed that IA-2 and IA-2 beta transcripts are highly but nonrhythmically expressed in the suprachiasmatic nuclei, the site of the brain's master circadian oscillator. Electrophysiological studies on tissue slices from the suprachiasmatic nuclei showed that disruption of both IA-2 and IA-2 beta results in significant alterations in neuronal firing. From these studies, we concluded that deletion of IA-2 and IA-2 beta, structural proteins of secretory vesicles and modulators of neuroendocrine secretion, has a profound effect on the circadian system.-Kim, S. M., Power, A., Brown, T. M., Constance, C. M., Coon, S. L., Nishimura, T., Hirai, H., Cai, T., Eisner, C., Weaver, D. R., Piggins, H. D., Klein, D. C., Schnermann, J., Notkins, A. L. Deletion of the secretory vesicle proteins IA-2 and IA-2 beta disrupts circadian rhythms of cardiovascular and physical activity. FASEB J. 23, 3226-3232 ( 2009). www.fasebj.org