Dept. of Physiological Sciences, Federal University of Espírito Santo, Vitória, ES CEP 29043-900, Brazil.
Dept. of Physiological Sciences, Federal University of Espírito Santo, Vitória, ES CEP 29043-900, Brazil; Health Science Center of Vitória-EMESCAM, Vitória, ES CEP 29045-402, Brazil.
Toxicol In Vitro. 2018 Sep;51:106-113. doi: 10.1016/j.tiv.2018.05.007. Epub 2018 May 14.
Copper is an essential metal for homeostasis and the functioning of living organisms. We investigated the effects of a high copper concentration on the myocardial mechanics, investigating the reactive oxygen species (ROS) mediated effects. The developed force of papillary muscles was reduced after acute exposure to a high copper concentration and was prevented by co-incubation with tempol, DMSO and catalase. The reuptake of calcium by the sarcoplasmic reticulum was reduced by copper and restored by tempol. The contractile response to Ca was reduced and reversed by antioxidants. The response to the β-adrenergic agonist decreased after exposure to copper and was restored by tempol and catalase. In addition, the in situ detection showed increased O- and OH. Contractions dependent on the sarcolemmal Ca influx were impaired by copper and restored by antioxidants. Myosin-ATPase activity decreased significantly after copper exposure. In conclusion, a high copper concentration can acutely impair myocardial excitation-contraction coupling, reduce the capacity to generate force, reduce the Ca inflow and its reuptake, and reduce myosin-ATPase activity, and these effects are mediated by the local production of O-, OH and HO. These toxicity effects of copper overload suggest that copper is a risk factor for cardiovascular disease.
铜是维持体内平衡和生物功能的必需金属。我们研究了高浓度铜对心肌力学的影响，研究了活性氧（ROS）介导的作用。急性暴露于高浓度铜后，乳头肌的收缩力降低，并用 Tempo1、DMSO 和过氧化氢酶共同孵育可预防收缩力降低。铜可减少肌浆网对钙的重摄取，并用 Tempo1 恢复。抗氧化剂可降低和逆转钙引起的收缩反应。β-肾上腺素能激动剂暴露后，对 Ca 的反应降低，用 Tempo1 和过氧化氢酶恢复。此外，原位检测显示 O-和 OH 增加。铜可损害依赖于肌浆网 Ca 内流的收缩，并通过抗氧化剂恢复。铜暴露后肌球蛋白-ATP 酶活性显著降低。总之，高浓度铜可急性损害心肌兴奋-收缩偶联，降低产生力的能力，减少 Ca 内流及其重摄取，并降低肌球蛋白-ATP 酶活性，这些作用是由局部产生的 O-、OH 和 HO 介导的。铜过载的这些毒性作用表明铜是心血管疾病的一个危险因素。
