Homocysteine restricts copper availability leading to suppression of cytochrome C oxidase activity in phenylephrine-treated cardiomyocytes.
Homocysteine restricts copper availability leading to suppression of cytochrome C oxidase activity in phenylephrine-treated cardiomyocytes.
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DOI：
10.1371/journal.pone.0067549
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kang YJ
中科院分区：
文献类型：
--
作者：
Zuo X;Dong D;Sun M;Xie H;Kang YJ
苯肾上腺素(PE)诱导的心肌细胞肥大伴随着细胞色素C氧化酶(CCO)活性的抑制，补充铜可恢复CCO活性并逆转其肥大。本研究旨在了解PE引起CCO活性降低的机制。用终浓度为100µM的PE处理原代培养的乳鼠心肌细胞72h，诱导细胞肥大。用酶法检测CCO活性，用Western blotting检测CCO亚基COX-IV和CCO铜伴侣蛋白(COX17、SCO2和COX11)的变化。PE处理提高了胞内和胞外同型半胱氨酸浓度，降低了胞内铜浓度。体外研究发现，同型半胱氨酸与铜形成络合物。抑制细胞内同型半胱氨酸的合成可阻止细胞外同型半胱氨酸浓度的升高，保持细胞内铜浓度，并保持CCO活性。PE处理降低了COX-IV、铜伴侣蛋白COX17、COX11和SCO2的蛋白浓度。这些PE效应可通过抑制细胞内同型半胱氨酸合成或补充铜来阻止。因此，PE诱导的同型半胱氨酸的升高通过与铜的相互作用和铜伴侣的抑制而限制了铜的有效性，导致CCO酶活性的下降。
Cardiomyocyte hypertrophy induced by phenylephrine (PE) is accompanied by suppression of cytochrome c oxidase (CCO) activity, and copper (Cu) supplementation restores CCO activity and reverses the hypertrophy. The present study was aimed to understand the mechanism of PE-induced decrease in CCO activity. Primary cultures of neonatal rat cardiomyocytes were treated with PE at a final concentration of l00 µM in cultures for 72 h to induce cell hypertrophy. The CCO activity was determined by enzymatic assay and changes in CCO subunit COX-IV as well as copper chaperones for CCO (COX17, SCO2, and COX11) were determined by Western blotting. PE treatment increased both intracellular and extracellular homocysteine concentrations and decreased intracellular Cu concentrations. Studies in vitro found that homocysteine and Cu form complexes. Inhibition of the intracellular homocysteine synthesis in the PE-treated cardiomyocytes prevented the increase in the extracellular homocysteine concentration, retained the intracellular Cu concentration, and preserved the CCO activity. PE treatment decreased protein concentrations of the COX-IV, and the Cu chaperones COX17, COX11, and SCO2. These PE effects were prevented by either inhibition of the intracellular homocysteine synthesis or Cu supplementation. Therefore, PE-induced elevation of homocysteine restricts Cu availability through its interaction with Cu and suppression of Cu chaperones, leading to the decrease in CCO enzyme activity.
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影响因子：
4.8
作者：
Horng, YC;Cobine, PA;Winge, DR
通讯作者：
Winge, DR
DOI：
10.1016/s1570-0232(02)00401-4
发表时间：
2002-11-05
影响因子：
3
作者：
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作者：
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DOI：
10.1016/0305-0491(94)00226-k
发表时间：
1995-05-01
影响因子：
2.2
作者：
LIAO, ZM;ALLRED, J;MEDEIROS, DM
通讯作者：
MEDEIROS, DM