Exercise and Doxorubicin Modify Markers of Iron Overload and Cardiolipin Deficiency in Cardiac Mitochondria.
Exercise and Doxorubicin Modify Markers of Iron Overload and Cardiolipin Deficiency in Cardiac Mitochondria.
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DOI：
10.3390/ijms24097689
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发表时间：
2023-04-22
影响因子：
5.6
通讯作者：
Smuder, Ashley J.
中科院分区：
文献类型：
--
作者：
Montalvo, Ryan N.;Boeno, Franccesco P.;Dowllah, Imtiaz M.;Moritz, Cesar E. Jacintho;Nguyen, Branden L.;Doerr, Vivian;Bomkamp, Matthew P.;Smuder, Ashley J.
阿霉素（DOX）是一种化疗药物，在限制癌症进展方面非常有效。尽管这种抗癌药物有疗效，但由于心脏毒性，DOX的临床应用受到限制。心脏线粒体是DOX的主要靶点，导致电子传递系统复合物失活、氧化应激和铁过载。然而，已经确定的是，心脏线粒体亚群对DOX暴露表现出不同的反应，其中肌下（SS）线粒体表现出氧化还原失衡，肌间纤维（IMF）线粒体表现出呼吸减少。因此，运动训练是预防dox诱发心功能障碍的有效干预手段。虽然很明显，运动可以提供线粒体保护，但目前尚不清楚运动训练是否通过促进SS和IMF线粒体的有益适应来减轻DOX心脏线粒体毒性。为了验证这一点，从暴露于急性DOX治疗的久坐和运动预处理的雌性Sprague Dawley大鼠中分离出SS和IMF线粒体。我们的研究结果显示，与IMF相比，运动预处理对dox处理大鼠SS线粒体氧化还原平衡和铁处理的影响更大，并在两个亚群中拯救心磷脂合成酶1的表达。这些结果表明，运动预处理与DOX治疗相结合可以改善线粒体稳态，并且与IMF线粒体相比，SS线粒体表现出更大的保护作用。这些数据为运动诱导的抗DOX毒性保护的分子机制提供了重要的见解。
Doxorubicin (DOX) is a chemotherapeutic agent highly effective at limiting cancer progression. Despite the efficacy of this anticancer drug, the clinical use of DOX is limited due to cardiotoxicity. The cardiac mitochondria are implicated as the primary target of DOX, resulting in inactivation of electron transport system complexes, oxidative stress, and iron overload. However, it is established that the cardiac mitochondrial subpopulations reveal differential responses to DOX exposure, with subsarcolemmal (SS) mitochondria demonstrating redox imbalance and the intermyofibrillar (IMF) mitochondria showing reduced respiration. In this regard, exercise training is an effective intervention to prevent DOX-induced cardiac dysfunction. Although it is clear that exercise confers mitochondrial protection, it is currently unknown if exercise training mitigates DOX cardiac mitochondrial toxicity by promoting beneficial adaptations to both the SS and IMF mitochondria. To test this, SS and IMF mitochondria were isolated from sedentary and exercise-preconditioned female Sprague Dawley rats exposed to acute DOX treatment. Our findings reveal a greater effect of exercise preconditioning on redox balance and iron handling in the SS mitochondria of DOX-treated rats compared to IMF, with rescue of cardiolipin synthase 1 expression in both subpopulations. These results demonstrate that exercise preconditioning improves mitochondrial homeostasis when combined with DOX treatment, and that the SS mitochondria display greater protection compared to the IMF mitochondria. These data provide important insights into the molecular mechanisms that are in part responsible for exercise-induced protection against DOX toxicity.
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影响因子：
3.8
作者：
GOORMAGHTIGH, E;HUART, P;RUYSSCHAERT, JM
通讯作者：
RUYSSCHAERT, JM
DOI：
10.3390/antiox11102073
发表时间：
2022-10-20
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
--
作者：
通讯作者：
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影响因子：
6
作者：
通讯作者：
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影响因子：
4.4
作者：
Marques-Aleixo, Ines;La Santos-Alves, Este;Ascensao, Antonio
通讯作者：
Ascensao, Antonio
影响因子：
4.1
作者：
MARCILLAT, O;ZHANG, Y;DAVIES, KJA
通讯作者：
DAVIES, KJA