Effect of thyroid status on thin-filament Ca2+ regulation and expression of troponin I in perinatal and adult rat hearts.

Effect of thyroid status on thin-filament Ca2+ regulation and expression of troponin I in perinatal and adult rat hearts.
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DOI:
10.1161/01.res.67.2.344
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发表时间:
1990-08
影响因子:
20.1
通讯作者:
L J Dieckman;R J Solaro
L J Dieckman;R J Solaro
中科院分区:
医学1区
文献类型:
--
作者:
L J Dieckman;R J Solaro

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有证据表明心肌细丝肌钙蛋白I(TnI)的表达存在发育性变化;然而,TnI表达的调节尚未被描述。我们用6-正丙基-2-硫氧嘧啶治疗甲状腺功能低下的新生和成年大鼠,测试了甲状腺状态是否影响TnI的表达。来自7日龄、14日龄、21日龄和28日龄动物心脏的肌原纤维的聚丙烯酰胺凝胶表明,甲状腺功能正常和甲状腺功能低下的大鼠都显示出向成年型TnI的发育转变。然而,在所研究的每个年龄段,甲状腺功能低下的大鼠显示出较低的成年TNI百分比。当成年大鼠甲状腺功能减退时,成年TnI所占比例略有下降。通过测定酸性pH对钙激活肌原纤维ATPase活性的影响来测定细丝活性。通过pCa50(半最大活化摩尔钙离子的对数)在pH 7.0和6.5之间的移动幅度来衡量对酸性pH的敏感性。正常甲状腺大鼠的pH敏感度呈发育性增加。在发育7、14和28天,pCa50的移动量分别为0.11、0.38和0.43个单位。甲状腺功能低下大鼠在发育第7、14和28天表现出较低的pH敏感性,pCa50分别移动了0.07、0.21和0.15个单位。成年甲状腺功能减退大鼠的pCa50有0.38个单位的移位,而正常甲状腺的成年大鼠则有0.44个单位的移位。我们的结果表明,心脏的pH敏感性和TnI的表达受发育阶段和激素状态的影响。
There is evidence for the existence of developmental changes in expression of troponin I (TNI) in cardiac thin filaments; however, regulation of TNI expression has not been described. We tested whether thyroid state affects expression of TNI using neonatal and adult rats made hypothyroid by treatment with 6-n-propyl-2-thiouracil. Polyacrylamide gels of myofibrils from hearts of 7-, 14-, 21-, and 28-day-old animals indicated that both euthyroid and hypothyroid rats display a developmental shift toward the adult form of TNI. However, hypothyroid rats displayed a lower percentage of adult TNI at each age studied. When adult rats were made hypothyroid, the proportion of adult TNI decreased slightly. Thin-filament activity was determined from measurements of the effect of acidic pH on calcium activation of myofibrillar ATPase activity. Sensitivity to acidic pH was measured by the magnitude of shift in pCa50 (-log of half-maximally activating molar Ca2+) between pH 7.0 and 6.5. Euthyroid rats displayed developmental increases in pH sensitivity. At 7, 14, and 28 days of development, shifts in pCa50 were 0.11, 0.38, and 0.43 units, respectively. Hypothyroid rats displayed less pH sensitivity with pCa50 shifts of 0.07, 0.21, and 0.15 units at 7, 14, and 28 days of development. Adult hypothyroid rats displayed a 0.38-unit shift in pCa50, whereas euthyroid adults displayed a 0.44-unit shift. Our results indicate that pH sensitivity and expression of cardiac TNI are influenced by developmental stage and hormonal status.