The fall in creatine levels and creatine kinase isozyme changes in the failing heart are reversible: complex post-transcriptional regulation of the components of the CK system.
The fall in creatine levels and creatine kinase isozyme changes in the failing heart are reversible: complex post-transcriptional regulation of the components of the CK system.
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衰竭心脏中肌酸水平的下降和肌酸激酶同工酶的变化是可逆的：CK 系统成分的复杂转录后调节。
DOI：
10.1016/j.yjmcc.2005.05.003
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发表时间：
2005
影响因子：
5
通讯作者：
Ingwall,JoanneS
中科院分区：
文献类型：
--
作者：
Shen,Weiqun;Spindler,Matthias;Higgins,MarnieA;Jin,Najia;Gill,RobertM;Bloem,LauraJ;Ryan,TimothyP;Ingwall,JoanneS
总肌酸激酶 (CK) 活性和肌酸 [Cr] 的降低共同限制了衰竭心脏快速重新合成 ATP（能量储备）的能力。如果能量储备的损失可以逆转，心脏收缩储备可能会得到改善。在这里，我们测试这些变化在心力衰竭恢复过程中是否可逆。左心室 (LV) 收缩功能是在长期接受仪器监测、患有心力衰竭 (CHF) 的、由心脏起搏引起的心力衰竭 (CHF) 犬中测量的，持续 3-4 周，以及心力衰竭恢复 (Recovery)（无起搏）后 5-6 周。 CHF 时左心室收缩功能和收缩储备下降，但在恢复时恢复控制。由于 [Cr] (–39%) 和 CK 活性 (–25%) 下降，CHF 中 CK 容量下降了 55%，但在恢复期完全恢复。 CHF 中的 CK-B 同工酶活性、蛋白质（Western）和 mRNA 水平（实时 PCR）分别高出 2 倍、5.4 倍和 11 倍，而恢复中则分别高出 3 倍、2 倍和 2 倍。 CHF 时 CK-MM 活性降低 (–30%)，但在恢复期间恢复到正常水平；尽管 mRNA 水平没有变化，但 CHF 和恢复期的 CK-M 蛋白均降低了 30%。线粒体 CK (sMtCK) 也发现了类似的模式。 CHF 中 CK 活性和 [Cr] 的降低是可逆的。 CK-MM 和 sMtCK 活性的降低，但 CK-BB 和 CK-MB 的增加，也发生逆转。 CK-B 和 CK-M 的蛋白质和 mRNA 水平的变化均与其活性无关，表明 CK 处于复杂的转录后调控之下。
Decreases in total creatine kinase (CK) activity and creatine [Cr] combine to limit the capacity of the failing heart to rapidly re-synthesize ATP (energy reserve). If the loss in energy reserve could be reversed, cardiac contractile reserve may be improved. Here we test whether these changes are reversible during recovery from heart failure. Left ventricular (LV) contractile function was measured in chronically instrumented conscious dogs with heart failure (CHF) induced by cardiac pacing for 3–4 weeks, and after recovery from heart failure (Recovery) (unpaced) for 5–6 weeks. LV contractile function and contractile reserve were depressed in CHF but returned to control in Recovery. CK capacity fell by 55% in CHF due to decreases in [Cr] (–39%) and CK activity (–25%), but was fully restored in Recovery. CK-B isozyme activity, protein (Western) and mRNA levels (real time PCR), respectively, were higher by 2-, 5.4- and 11-fold in CHF and higher by 3-, 2- and 2-fold in Recovery. CK-MM activity was decreased (–30%) in CHF but returned to normal levels during Recovery; CK-M protein was 30% lower in both CHF and Recovery even though there were no changes in mRNA levels. A similar pattern was found for mitochondrial CK (sMtCK). Deceases in CK activity and [Cr] in CHF are reversible. Decreases in CK-MM and sMtCK activities, but not the increases in CK-BB and CK-MB, also reversed. Neither the changes in protein nor mRNA levels for CK-B and CK-M correlated to their activities, suggesting that CK is under complex post-transcriptional regulation.