Fluorosed mouse ameloblasts have increased SATB1 retention and Gαq activity.
Fluorosed mouse ameloblasts have increased SATB1 retention and Gαq activity.
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DOI：
10.1371/journal.pone.0103994
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Den Besten PK
中科院分区：
文献类型：
--
作者：
Zhang Y;Kim JY;Horst O;Nakano Y;Zhu L;Radlanski RJ;Ho S;Den Besten PK
氟斑牙的特征是表面下矿化不足和釉质孔隙度增加，与釉质基质蛋白的去除延迟有关。为了研究氟化物对成釉细胞的影响，A/J小鼠在饮用水中给予50 ppm的氟化钠，持续四周，导致血清氟化物水平为4.5 µM，是对照组小鼠的四倍。MicroCT分析显示，与对照釉质相比，氟化切牙釉质的矿化延迟和不完全。微阵列分析的分泌和成熟阶段的成釉细胞显微解剖控制和氟小鼠切牙显示，与Mmp 20聚集的基因似乎是在成熟阶段的成釉细胞的氟切牙相比，控制成熟成釉细胞下调。这些Mmp 20共调节基因之一是全球染色质组织者，特殊的富含AT的序列结合蛋白1（SATB 1）。免疫组化分析显示，增加SATB 1蛋白存在于氟成釉细胞相比，对照组。在体外，暴露于微摩尔水平的氟化钠和氟化铝的人成釉细胞系细胞导致SATB 1蛋白含量的显着增加，但不是Satb 1 mRNA的水平，这表明氟化物诱导的机制保护SABT 1降解。与这种可能性相一致，我们使用免疫组织化学和蛋白质印迹显示，氟暴露的成釉细胞在体内和体外都增加了磷酸化PKCα。已知该激酶磷酸化SATB 1，并且已知磷酸化保护SATB 1免于被半胱天冬酶-6降解。另外，氟暴露后成釉细胞甘油二酯（diacylglycerol，DAG）的生成显著增加，提示SATB 1磷酸化水平的增加可能与氟增强分泌型成釉细胞Gαq活性有关。
Dental fluorosis is characterized by subsurface hypomineralization and increased porosity of enamel, associated with a delay in the removal of enamel matrix proteins. To investigate the effects of fluoride on ameloblasts, A/J mice were given 50 ppm sodium fluoride in drinking water for four weeks, resulting serum fluoride levels of 4.5 µM, a four-fold increase over control mice with no fluoride added to drinking water. MicroCT analyses showed delayed and incomplete mineralization of fluorosed incisor enamel as compared to control enamel. A microarray analysis of secretory and maturation stage ameloblasts microdissected from control and fluorosed mouse incisors showed that genes clustered with Mmp20 appeared to be less downregulated in maturation stage ameloblasts of fluorosed incisors as compared to control maturation ameloblasts. One of these Mmp20 co-regulated genes was the global chromatin organizer, special AT-rich sequence-binding protein-1 (SATB1). Immunohistochemical analysis showed increased SATB1 protein present in fluorosed ameloblasts compared to controls. In vitro, exposure of human ameloblast-lineage cells to micromolar levels of both NaF and AlF3 led to a significantly increase in SATB1 protein content, but not levels of Satb1 mRNA, suggesting a fluoride-induced mechanism protecting SABT1 from degradation. Consistent with this possibility, we used immunohistochemistry and Western blot to show that fluoride exposed ameloblasts had increased phosphorylated PKCα both in vivo and in vitro. This kinase is known to phosphorylate SATB1, and phosphorylation is known to protect SATB1 from degradation by caspase-6. In addition, production of cellular diacylglycerol (DAG) was significantly increased in fluorosed ameloblasts, suggesting that the increased phosphorylation of SATB1 may be related to an effect of fluoride to enhance Gαq activity of secretory ameloblasts.
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影响因子：
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通讯作者：
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作者：
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通讯作者：
DENBESTEN, PK