Na-PUMP GENE EXPRESSION IN HYPERTROPHIC HEARTS

肥厚心脏中钠泵基因的表达

• 批准号: 02670407
• 负责人: IKEDA Uichi
• 金额: $ 1.6万
• 依托单位: JICHI MEDICAL SCHOOL
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670407/
• 关键词: Cardiac hypertrophy; Cardiomyopathy; Na, K-ATPase; Sodium pump; Na,KーATPase; 甲状腺ホルモン; アルドステロン; NaKーATPase

Na, K-ATPase (Na, K-pump) maintains intracellular ion composition by transporting Na^+ and K^+across the cell membrance, and plays an important role in many fundamental cellular and physiological processes such as the control of contractility, excitability, and cell volume regulation. The Na, K-ATPase protein comprises two subunits, a large catalytic alpha subunit and a smaller glycosylated beta subunit. At least three alpha subunit isoforms, alpha1, alpha2 and alpha3, and two beta subunit isoforms, beta1 and beta2, have been characterized in rats and humans. With the support of the Grant-in-Aid fro Scientific Research (A), we have revealed that ; (1) The expression of Na, K-ATPase alpha and beta subunits in cardiocytes in vitro was directly regulated at a transcriptional level by thyroid and aldosterone hormones, or Na^+, (2) In the hypertrophic hearts of spontaneously hypertensive rats (SHR), Na, K-ATPase mRNA expression was augmented compared with normotensive rats (WKY) at the pre-hypertensive stage of 4-week-old, (3) In the in vivo failing hearts of Syrian hamsters (Bio14.6), the expression of cardiac Na, K-ATPase gene was down-regulated compared with normal hamsters (Flb). Thus the alterations of Na, K-ATPase gene expression might play an important roll in the pathogenesis of cardiac hypertrophy and cardiomyopathy.

Na,K-ATP酶（Na,K-泵）通过跨细胞膜运输Na^+和K^+来维持细胞内离子组成，并在许多基本细胞和生理过程中发挥重要作用，例如控制收缩性、兴奋性和细胞体积调节。 Na,K-ATP酶蛋白包含两个亚基，一个大的催化α亚基和一个较小的糖基化β亚基。至少三种 α 亚基亚型（α1、α2 和 α3）以及两种 β 亚基亚型（β1 和 β2）已在大鼠和人类中进行了表征。在科学研究补助金 (A) 的支持下，我们透露： (1) 体外心肌细胞中 Na, K-ATPase α 和 β 亚基的表达在转录水平上受到甲状腺和醛固酮激素或 Na^+ 的直接调节，(2) 在自发性高血压大鼠 (SHR) 的肥厚心脏中，与高血压前期的正常血压大鼠 (WKY) 相比，Na, K-ATPase mRNA 表达增强 4周龄时，(3)在体内衰竭的叙利亚仓鼠(Bio14.6)心脏中，与正常仓鼠(Flb)相比，心脏Na,K-ATPase基因的表达下调。因此，Na、K-ATP酶基因表达的改变可能在心脏肥大和心肌病的发病机制中发挥重要作用。

项目成果

Keiji Yamamoto: "Regulation of Na,K-ATPase gene expression by sodiam ions in cultured nesnatal rat cardiogr" Journal of Clinical Investigation.

Keiji Yamamoto：“培养新生大鼠心脏中钠离子对 Na,K-ATP 酶基因表达的调节”临床研究杂志。

Uichi Ikeda: "α1 adrenergic stimulation is coupled to cardiac myocyte hypertrophy" American Journal of Physiology. 260. H953-H956 (1991)

Uichi Ikeda：“α1 肾上腺素刺激与心肌细胞肥大相关”美国生理学杂志 260. H953-H956 (1991)。

Uichi Ikeda: "Cardiomyopathy upto Date" Tokyo Universty Press, (1993)

池田宇一：《最新的心肌病》东京大学出版社，（1993）

Uichi Ikeda: "Aldosteroneーmediated regulation of Na,KーTAPase gene expression in adult and neonatal rat cardiocytes" Journal of Biological Chemistry. 266. 12058-12066 (1991)

Uichi Ikeda：“成年和新生大鼠心肌细胞中醛固酮介导的 Na,K-TAPase 基因表达调节”《生物化学杂志》266。12058-12066 (1991)

Uichi Ikeda: "Uentricular cells in culture from adult spontareously hypertansive rats exhibit decreased growth" Journal of Hypertsnsion. 8. 1003-1006 (1990)

Uichi Ikeda：“成年自发性高血压大鼠培养物中的肾小球细胞表现出生长下降”《高血压杂志》。