Expressional analysis of the cardiac Na-Ca exchanger in rat development and senescence
Expressional analysis of the cardiac Na-Ca exchanger in rat development and senescence
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DOI：
10.1016/s0008-6363(97)00276-9
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发表时间：
1998-02-01
影响因子：
10.8
通讯作者：
Boheler, KR
中科院分区：
文献类型：
--
作者：
Koban, MU;Moorman, AFM;Boheler, KR
心脏钠钙交换器（NCX）是心肌细胞内主要的钙外排机制，在维持细胞内钙稳态中起重要作用。已知NCX RNA和蛋白质的积累在心脏肥大、甲状腺激素和出生后发育期间受到调节。在这项研究中，NCX mRNA和蛋白质积累的时间和空间模式进行了检查，并进行核运行试验。NCX在晚期胎儿和新生大鼠心脏中高度表达，RNA在出生后20天降低至成人水平（P < 0.05，胎儿和1天龄新生大鼠（1 ND）对20天龄新生大鼠（20 ND））。最大蛋白质表达见于19个胚胎日龄（艾德）的心脏，并在20个新生日龄后的某个时候达到成人水平。（P < 0.05，胎儿与成人）。在空间上，NCX在早期胚胎和胎儿心脏中均匀表达，出生后表达下降。蛋白质水平下降更慢，表明蛋白质半衰期长。在6月龄和18月龄的动物中观察到最低水平的mRNA积累（对于10个新生日之前的所有时间点，P < 0.05）。在24月龄的衰老大鼠中，NCX转录物比6和18月龄时增加了近50%（P < 0.05），但与新生15天的那些没有差异。围产期NCX表达受转录调控：晚期胎儿和新生儿心脏具有高转录活性，但到出生后20天，无法检测到转录活性。在整个开发过程中，至少使用了5个转录起始位点，尽管鉴定了几种新的心脏剪接变体，但在5'非翻译或3'编码剪接位点中没有显着差异。我们还报告了一个3.7 kb的片段，包含心脏NCX1启动子，这是在新生儿心肌细胞转录活性的克隆。(C)1998年Elsevier Science B.V.
The cardiac Na-Ca exchanger (NCX) serves as the main calcium extrusion mechanism in heart muscle and is important in maintaining intracellular calcium homeostasis. The accumulations of NCX RNA and protein are known to be regulated in cardiac hypertrophy, by thyroid hormone and during postnatal development. In this study the temporal and spatial patterns of NCX mRNA and protein accumulations were examined, and nuclear run-on assays performed. NCX is highly expressed in late fetal and neonatal rat hearts, decreasing to adult levels by 20 days after birth for RNA (P < 0.05, fetal and 1 neonatal day old (1 ND) versus 20 day old (20 ND)). Maximal protein expression is seen in 19 embryonic day (ED) old hearts, and reaches adult levels sometime after 20 neonatal days. (P < 0.05, fetal versus adult). Spatially, NCX is homogenously expressed in early embryonic and fetal heart, followed by a decline after birth. The protein levels decline more slowly suggesting a long protein half-life. The lowest level of mRNA accumulation is seen in 6 and 18 month old animals (P < 0.05 for all time points before 10 neonatal days). In the 24 month old senescent rat, NCX transcripts are increased by almost 50% above that seen at 6 and 18 months (P < 0.05) but are not different from those at 15 neonatal days. Perinatal NCX expression is regulated transcriptionally: late fetal and neonatal hearts have high transcriptional activity but by 20 postnatal days, no detectable transcriptional activity can be demonstrated. Throughout development, at least five transcription start sites are used, and no significant difference in the 5' untranslated or 3' coding splice sites could be demonstrated, although several new cardiac splicing variants were identified. We also report the cloning of a 3.7 kb fragment containing the cardiac NCX1 promoter which is transcriptionally active in neonatal cardiomyocytes. (C) 1998 Elsevier Science B.V.