Counteraction of Myocardial Ferritin Heavy Chain Deficiency by Heme Oxygenase-1.
Counteraction of Myocardial Ferritin Heavy Chain Deficiency by Heme Oxygenase-1.
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DOI：
10.3390/ijms23158300
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发表时间：
2022-07-27
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
鉴于血红素蛋白（细胞色素）在心脏中的丰度，很明显，精心策划的铁代谢对心脏健康至关重要。在这里，我们研究了心肌铁蛋白重链（FtH）在急性心肌梗死模型中的功能意义。我们报告说，FtH的缺失没有改变线粒体的调节和监视途径（裂变和融合）或线粒体生物能量响应损伤。此外，心肌FtH的删除并没有影响心脏功能，通过测量左心室射血分数，在第1，7，和21天损伤后。为了鉴定与FtH缺失同时提供心肌细胞保护的调节途径，我们进行了无偏转录组学分析。我们发现，损伤后，FtH缺失与几个基因的上调与抗铁蛋白特性，包括血红素加氧酶-1（HO-1）和胱氨酸/谷氨酸反向转运蛋白（Slc 7a 11）。这些结果表明HO-1过表达通过上调Slc 7a 11减轻铁凋亡。事实上，使用HO-1过表达的转基因小鼠，我们证明过表达的HO-1与Slc 7a 11表达增加相结合。总之，我们表明，损伤后，心肌FtH缺失导致补偿性上调的一些抗铁蛋白基因，包括HO-1。这种HO-1诱导导致Slc 7a 11的过表达，并保护心脏免受缺血再灌注介导的铁凋亡，保护线粒体功能和心肌的整体功能。
Given the abundance of heme proteins (cytochromes) in the mitochondrion, it is evident that a meticulously orchestrated iron metabolism is essential for cardiac health. Here, we examined the functional significance of myocardial ferritin heavy chain (FtH) in a model of acute myocardial infarction. We report that FtH deletion did not alter either the mitochondrial regulatory and surveillance pathways (fission and fusion) or mitochondrial bioenergetics in response to injury. Furthermore, deletion of myocardial FtH did not affect cardiac function, assessed by measurement of left ventricular ejection fraction, on days 1, 7, and 21 post injury. To identify the modulated pathways providing cardiomyocyte protection coincident with FtH deletion, we performed unbiased transcriptomic analysis. We found that following injury, FtH deletion was associated with upregulation of several genes with anti-ferroptotic properties, including heme oxygenase-1 (HO-1) and the cystine/glutamate anti-porter (Slc7a11). These results suggested that HO-1 overexpression mitigates ferroptosis via upregulation of Slc7a11. Indeed, using transgenic mice with HO-1 overexpression, we demonstrate that overexpressed HO-1 is coupled with increased Slc7a11 expression. In conclusion, we demonstrate that following injury, myocardial FtH deletion leads to a compensatory upregulation in a number of anti-ferroptotic genes, including HO-1. Such HO-1 induction leads to overexpression of Slc7a11 and protects the heart against ischemia-reperfusion-mediated ferroptosis, preserves mitochondrial function, and overall function of the myocardium.
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影响因子：
5.6
作者：
Balla J;Zarjou A
通讯作者：
Zarjou A
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
用于定量小鼠心脏体内缺血再灌注损伤的精制方法。
DOI：
10.1152/ajpheart.00836.2009
发表时间：
2009-12
期刊：
American journal of physiology. Heart and circulatory physiology
影响因子：
--
作者：
Bohl S;Medway DJ;Schulz-Menger J;Schneider JE;Neubauer S;Lygate CA
通讯作者：
Lygate CA
DOI：
10.1136/heartjnl-2015-307855
发表时间：
2016-03
期刊：
Heart (British Cardiac Society)
影响因子：
--
作者：
Bulluck H;Yellon DM;Hausenloy DJ
通讯作者：
Hausenloy DJ
影响因子：
4.8
作者：
Ferreira, C;Bucchini, D;Beaumont, C
通讯作者：
Beaumont, C