Effects of luteolin on regulatory proteins and enzymes for myocyte calcium circulation in hypothermic preserved rat heart.
Effects of luteolin on regulatory proteins and enzymes for myocyte calcium circulation in hypothermic preserved rat heart.
复制标题
木犀草素对低温保存大鼠心脏肌细胞钙循环调节蛋白和酶的影响
DOI：
10.3892/etm.2017.5514
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发表时间：
2018-03
影响因子：
2.7
通讯作者：
Liu S
中科院分区：
文献类型：
--
作者：
Yan Q;Li Y;Yan J;Zhao Y;Liu Y;Liu S
心脏移植作为治疗终末期心力衰竭患者的最佳方案已应用于临床多年。然而，心脏的低温保存仍然限于4-6小时，并且钙随时间的积累是导致细胞死亡的重要因素。为了使供心保存时间更长、更安全，我们前期的研究表明，用于治疗心血管疾病的中药毛地黄黄酮在低温保存过程中抑制细胞死亡和L型钙电流。在本研究中，进一步研究了毛地黄黄酮在调节心肌细胞钙循环中的保护作用。细胞内钙超载已被牵连在心肌细胞功能障碍引起的心肌细胞缺氧。使用补充有7.5、15或30 μmol/l木犀草素的威斯康星州大学（UW）溶液在4 ℃下保存新鲜分离的心肌细胞。结果表明，所有三种剂量的木樨草素补充剂在6小时的保存期内减弱了钙超载。木犀草素还抑制了心肌细胞钙循环的重要调节蛋白和酶、线粒体Ca 2+单向转运体和钙调蛋白的积累，这些蛋白和酶通常由UW溶液中的冷藏诱导。蛋白激酶A活性也受到抑制，而Ca 2 +-Mg 2 +-ATP酶活性增加，在保存在木犀草素补充UW液的心肌细胞。结果表明，毛地黄黄酮通过抑制低温保存过程中钙调节因子的变化，从而减轻心肌细胞内钙超载，从而发挥心肌保护作用。
Heart transplantation has been applied in the clinic as an optimal solution for patients with end stage cardiac failure for a number of years. However, hypothermic preservation of the heart remains limited to 4–6 h and calcium accumulation over time is an important factor resulting in cell death. To provide longer and safer storage for donor hearts, it was demonstrated in our previous study that luteolin, a traditional Chinese medicine used to treat cardiovascular diseases, inhibits cell death and L-type calcium currents during hypothermic preservation. In the current study, the protective role of luteolin in modulating cardiomyocyte calcium cycling was further investigated. Intracellular calcium overload has already been implicated in hypothermia-induced dysfunction of cardiomyocytes. University of Wisconsin (UW) solution supplemented with 7.5, 15 or 30 µmol/l luteolin was used to preserve fresh isolated cardiomyocytes at 4°C. The results demonstrated that all three doses of luteolin supplementation attenuated calcium overload over a 6 h preservation period. Luteolin also suppressed the accumulation of important regulatory proteins and enzymes for cardiomyocyte calcium circulation, mitochondria Ca2+ uniporter and calmodulin, which are normally induced by cold storage in UW solution. Protein Kinase A activity was also suppressed in cardiomyocytes preserved in luteolin supplemented UW solution, while Ca2+-Mg2+-ATPase activity was increased. The results demonstrated that luteolin confers a cardioprotective effect through inhibiting the changes of calcium regulators during cold storage and therefore ameliorates Ca2+ overload in rat cardiomyocytes.
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影响因子：
7.2
作者：
Fearnley, Claire J.;Roderick, H. Llewelyn;Bootman, Martin D.
通讯作者：
Bootman, Martin D.
影响因子：
4.8
作者：
Kimura, Y;Kurzydlowski, K;MacLennan, DH
通讯作者：
MacLennan, DH
影响因子：
4
作者：
Fusi, Fabio;Manetti, Fabrizio;Saponara, Simona
通讯作者：
Saponara, Simona
影响因子：
3
作者：
Lin Y;Shi R;Wang X;Shen HM
通讯作者：
Shen HM
影响因子：
3.6
作者：
Choi, Jun-Hui;Kim, Yoon-Sik;Kim, Seung
通讯作者：
Kim, Seung