Differential regulation of the myosin heavy chain genes α and β in rat atria and ventricles:: Role of antisense RNA
Differential regulation of the myosin heavy chain genes α and β in rat atria and ventricles:: Role of antisense RNA
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DOI：
10.1089/thy.2008.0043
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发表时间：
2008-07-01
期刊：
影响因子：
6.6
通讯作者：
Klein, Irwin
中科院分区：
文献类型：
--
作者：
Danzi, Sara;Klein, Steven;Klein, Irwin
背景：肌球蛋白重链 (MHC) 基因受三碘甲状腺原氨酸 (T-3) 以相互和腔室特异性的方式调节。为了进一步了解所涉及的潜在机制，我们测定了大鼠心室和心房中 MHC 基因、α 和 β 以及 β-MHC 反义 (AS) 基因的 T-3 反应性。方法：给甲状腺功能减退大鼠施用单次生理剂量 (1 μg) 或药理剂量 (20 μg) T-3，并连续测量来自大鼠心室和心房的 β-MHC hn- 和 AS RNA 以及 α-MHC 异质核 RNA结果：我们已经证明，T-3 处理可增加心房和心室中 AS beta-MHC RNA 的心肌细胞含量，其中包括与 beta-MHC 有义转录物的前 5' 和最后 3' 内含子互补的序列。在甲状腺功能减退的大鼠心室中，β-MHC sense RNA 表达最大，而在甲状腺功能正常的大鼠心室中，β-MHC AS RNA 表达最大。注射生理剂量的T-3（1μg/动物）后24小时，β-MHC AS表达在峰值处增加了52+/-9.8%，而β-MHC有义RNA在36小时（最低点）时减少了41+/-2.2%。在甲状腺功能减退症大鼠心房中，给予1μg T-3后6小时内β-MHC AS RNA被诱导三倍，表明在心房中，β-MHC AS表达受T-3调节，而α-MHC表达则不受T-3调节。结论：在甲状腺功能减退大鼠心室中，β-MHC AS RNA表达随着T-3的反应而增加，与α-MHC相似。 β-MHC 有义 RNA 的同时测量值减少，表明 AS 调节有义表达的可能机制。在心房中，虽然 α-MHC 不受甲状腺状态的影响，但 β-MHC 意义和 AS RNA 响应 T-3 同时反向改变。这证实了心房和心室中 T-3 和 β-MHC AS RNA 之间存在密切的正相关关系，同时首次证明 α-和 β-MHC 表达在心房中不耦合。
Background: The myosin heavy chain (MHC) genes are regulated by triiodothyronine (T-3) in a reciprocal and chamber-specific manner. To further our understanding of the potential mechanisms involved, we determined the T-3 responsiveness of the MHC genes, alpha and beta, and the beta-MHC antisense (AS) gene in the rat ventricles and atria.Methods: Hypothyroid rats were administered a single physiologic (1 mu g) or pharmacologic (20 mu g) dose of T-3, and sequential measurements of beta-MHC hn- and AS RNA and alpha-MHC heterogeneous nuclear RNA from rat ventricular and atrial myocardium were performed with reverse transcription PCR.Results: We have demonstrated that T-3 treatment increases the myocyte content of an AS beta-MHC RNA in atria and ventricles that includes sequences complementary to both the first 5' and last 3' introns of the beta-MHC sense transcript. In the hypothyroid rat ventricle, beta-MHC sense RNA expression is maximal, while in the euthyroid rat ventricle, beta-MHC AS RNA is maximal. beta-MHC AS expression increased by 52 +/- 9.8% at the peak, 24 hours after injection of a physiologic dose of T-3 (1 mu g/animal), while beta-MHC sense RNA decreased by 41 +/- 2.2% at 36 hours, the nadir. In hypothyroid atria, beta-MHC AS RNA was induced by threefold within 6 hours of administration of 1 mu g T-3, demonstrating that in the atria, beta-MHC AS expression is regulated by T-3, while alpha-MHC expression is not.Conclusions: In the hypothyroid rat heart ventricle, beta-MHC AS RNA expression increases in response to T-3 similar to that of alpha-MHC. Simultaneous measures of beta-MHC sense RNA are decreased, suggesting a possible mechanism for AS to regulate sense expression. In atria, while alpha-MHC is not influenced by thyroid state, beta-MHC sense and AS RNA were simultaneously and inversely altered in response to T-3. This confirms a close positive relationship between T-3 and beta-MHC AS RNA in both the atria and ventricles, while demonstrating for the first time that alpha-and beta-MHC expression is not coupled in the atria.