Knockdown of Mtfp1 can minimize doxorubicin cardiotoxicity by inhibiting Dnm1l-mediated mitochondrial fission.
Knockdown of Mtfp1 can minimize doxorubicin cardiotoxicity by inhibiting Dnm1l-mediated mitochondrial fission.
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DOI：
10.1111/jcmm.13250
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发表时间：
2017-12
影响因子：
5.3
通讯作者：
Li P
中科院分区：
文献类型：
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作者：
Aung LHH;Li R;Prabhakar BS;Li P
由于严重心肌病的发展，阿霉素(DOX)的长期使用在很大程度上受到了限制。大量研究表明，DOX所致的心脏损伤与活性氧的产生和细胞凋亡的最终激活有关。新的线粒体裂变蛋白1(Mtfp1)在DOX诱导的心脏毒性中的作用仍然不清楚。在这里，我们报告了Mtfp1在DOX诱导的心脏毒性中的促线粒体分裂和促凋亡作用。DOX上调HL-1心肌细胞Mtfp1表达。Mtfp1基因敲除可阻止心肌细胞发生线粒体分裂，进而通过阻止动力蛋白1样蛋白(Dnm1l)在线粒体中积聚来减少DOX诱导的细胞凋亡。相反，当Mtfp1过表达时，低于最佳剂量的DOX可以诱导相当大比例的细胞经历线粒体分裂和凋亡。这些数据表明，在DOX诱导的心脏毒性中，敲除Mtfp1可以最大限度地减少心肌细胞的损失。因此，调节Mtfp1的表达可能成为治疗化疗所致心脏毒性的新途径。
The long‐term usage of doxorubicin (DOX) is largely limited due to the development of severe cardiomyopathy. Many studies indicate that DOX‐induced cardiac injury is related to reactive oxygen species generation and ultimate activation of apoptosis. The role of novel mitochondrial fission protein 1 (Mtfp1) in DOX‐induced cardiotoxicity remains elusive. Here, we report the pro‐mitochondrial fission and pro‐apoptotic roles of Mtfp1 in DOX‐induced cardiotoxicity. DOX up‐regulates the Mtfp1 expression in HL‐1 cardiac myocytes. Knockdown of Mtfp1 prevents cardiac myocyte from undergoing mitochondrial fission, and subsequently reduces the DOX‐induced apoptosis by preventing dynamin 1‐like (Dnm1l) accumulation in mitochondria. In contrast, when Mtfp1 is overexpressed, a suboptimal dose of DOX can induce a significant percentage of cells to undergo mitochondrial fission and apoptosis. These data suggest that knocking down of Mtfp1 can minimize the cardiomyocytes loss in DOX‐induced cardiotoxicity. Thus, the regulation of Mtfp1 expression could be a novel therapeutic approach in chemotherapy‐induced cardiotoxicity.
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影响因子：
3.1
作者：
De Iuliis, Francesca;Salerno, Gerardo;Scarpa, Susanna
通讯作者：
Scarpa, Susanna
影响因子：
2.8
作者：
Nsiah-Sefaa, Abena;Brown, Erin L.;Foletta, Victoria C.
通讯作者：
Foletta, Victoria C.
影响因子：
2.9
作者：
KLEE, CB;KRINKS, MH
通讯作者：
KRINKS, MH
影响因子：
--
作者：
Corrado M;Scorrano L;Campello S
通讯作者：
Campello S
影响因子：
9
作者：
通讯作者：
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