Overexpression of RCAN1, a Gene on Human Chromosome 21, Alters Cell Redox and Mitochondrial Function in Enamel Cells.
Overexpression of RCAN1, a Gene on Human Chromosome 21, Alters Cell Redox and Mitochondrial Function in Enamel Cells.
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钙调神经磷酸酶（RCAN 1）的调节剂已被牵连在唐氏综合征（DS）的发病机制。患有DS的个体由于未知原因显示牙齿异常，并且已经发现在DS患者的几种组织中RCAN 1水平升高。先前的微阵列分析比较了牙釉质的两个主要形成阶段（分泌和成熟）的细胞，结果显示后者的RCAN 1表达显著增加。由于RCAN 1在釉质形成过程中的功能尚不清楚，因此没有将RCAN 1与DS患者的牙齿异常联系起来的机制证据。我们通过在成釉细胞系LS 8中过表达RCAN 1（LS 8 + RCAN 1）来研究RCAN 1在釉质中的作用。我们首先通过qRT-PCR证实RCAN 1在成熟期成釉细胞中高度表达，并使用免疫荧光显示其在成釉细胞中的定位。然后，我们分析了LS 8 + RCAN 1细胞中的细胞氧化还原和线粒体生物能量学，因为已知RCAN 1会影响这些过程。我们发现，LS 8 + RCAN 1细胞增加了活性氧（ROS）和减少线粒体生物能量学的电子传递链的复合物的表达，或在NADH水平没有变化。然而，LS 8 + RCAN 1细胞表现出线粒体Ca 2+摄取升高和釉质形成所必需的几个釉质基因的表达降低。这些结果提供了对RCAN 1在釉质中的作用的深入了解，并表明DS个体成釉细胞中RCAN 1水平的增加可能通过改变氧化还原环境和线粒体功能以及降低釉质特异性基因的表达来影响釉质形成。
The regulator of calcineurin (RCAN1) has been implicated in the pathogenesis of Down syndrome (DS). Individuals with DS show dental abnormalities for unknown reasons, and RCAN1 levels have been found to be elevated in several tissues of DS patients. A previous microarray analysis comparing cells of the two main formative stages of dental enamel, secretory and maturation, showed a significant increase in RCAN1 expression in the latter. Because the function of RCAN1 during enamel formation is unknown, there is no mechanistic evidence linking RCAN1 with the dental anomalies in individuals with DS. We investigated the role of RCAN1 in enamel by overexpressing RCAN1 in the ameloblast cell line LS8 (LS8+RCAN1). We first confirmed that RCAN1 is highly expressed in maturation stage ameloblasts by qRT-PCR and used immunofluorescence to show its localization in enamel-forming ameloblasts. We then analyzed cell redox and mitochondrial bioenergetics in LS8+RCAN1 cells because RCAN1 is known to impact these processes. We show that LS8+RCAN1 cells have increased reactive oxygen species (ROS) and decreased mitochondrial bioenergetics without changes in the expression of the complexes of the electron transport chain, or in NADH levels. However, LS8+RCAN1 cells showed elevated mitochondrial Ca2+ uptake and decreased expression of several enamel genes essential for enamel formation. These results provide insight into the role of RCAN1 in enamel and suggest that increased RCAN1 levels in the ameloblasts of individuals with DS may impact enamel formation by altering both the redox environment and mitochondrial function, as well as decreasing the expression of enamel-specific genes.
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影响因子：
7.4
作者：
Blacker, Thomas S.;Duchen, Michael R.
通讯作者：
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影响因子：
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影响因子：
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作者：
CHEN, LS;COUWENHOVEN, RI;SNEAD, ML
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通讯作者：
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