Transferrin-mediated increase of labile iron Pool following simulated ischemia causes lipid peroxidation during the early phase of reperfusion.

IF 3.6 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Free Radical Research Pub Date : 2022-11-01 DOI:10.1080/10715762.2023.2169683
Dongju Lee, Euncheol Son, Young-Hoon Kim
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Abstract

Heart ischemia/reperfusion (I/R) injury is related to iron content. However, the occurrence and mechanism of changes in labile iron pool (LIP) during I/R is debatable. Moreover, the identity of the iron form dominant in LIP during I/R is unclear. Herein, we measured changes of LIP during simulated ischemia (SI) and reperfusion (SR), in which ischemia was simulated in vitro with lactic acidosis and hypoxia. Total LIP did not change in lactic acidosis, whereas LIP, especially Fe3+, increased in hypoxia. Under SI, accompanied by hypoxia with acidosis, both Fe2+ and Fe3+ were significantly increased. Increased total LIP was maintained at 1 h post-SR. However, the Fe2+ and Fe3+ portion was changed. The increased Fe2+ was decreased, and conversely the Fe3+ was increased. BODIPY oxidized signal increased and through the time-course these changes correlated with blebbing of cell membrane and SR-induced LDH release. These data suggested lipid peroxidation occurred via Fenton's reaction. The experiments using bafilomycin A1 and zinc protoporphyrin suggested no role of ferritinophagy or heme oxidation in the increase of LIP during SI. The extracellular source, transferrin assessed using serum transferrin bound iron (TBI) saturation showed that the depletion of TBI reduced SR-induced cell damages and additive saturation of TBI accelerated SR-induced lipid peroxidation. Furthermore, Apo-Tf dramatically blocked the increase of LIP and SR-induced damages. In conclusion, Tf-mediated iron induces the increase of LIP during SI, and it causes Fenton reaction-mediated lipid peroxidation during the early phase of SR.

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模拟缺血后转铁蛋白介导的不稳定铁池增加导致再灌注早期脂质过氧化。
心脏缺血再灌注(I/R)损伤与铁含量有关。然而,在I/R过程中,不稳定铁池(LIP)变化的发生和机制尚存争议。此外,在I/R过程中LIP中占主导地位的铁形式的身份尚不清楚。我们在体外模拟乳酸酸中毒和缺氧的缺血过程中,测量了LIP在模拟缺血(SI)和再灌注(SR)过程中的变化。乳酸酸中毒时总LIP没有变化,而缺氧时LIP,尤其是Fe3+升高。SI下,伴缺氧酸中毒,Fe2+和Fe3+均显著升高。总LIP在sr后1 h保持升高。而Fe2+和Fe3+部分发生了变化。增加的Fe2+减少,相反的Fe3+增加。BODIPY氧化信号增加,并随着时间的推移,这些变化与细胞膜起泡和sr诱导的LDH释放相关。这些数据表明脂质过氧化是通过芬顿反应发生的。使用巴霉素A1和原卟啉锌的实验表明,铁蛋白吞噬和血红素氧化在SI期间LIP的增加中没有作用。细胞外来源,通过血清转铁蛋白结合铁(TBI)饱和度评估转铁蛋白显示,TBI的消耗减少了sr诱导的细胞损伤,TBI的添加饱和加速了sr诱导的脂质过氧化。此外,Apo-Tf显著阻断了LIP和sr诱导的损伤的增加。综上所述,tf介导的铁诱导SI期间LIP升高,并在SR早期引起Fenton反应介导的脂质过氧化。
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来源期刊
Free Radical Research
Free Radical Research 生物-生化与分子生物学
CiteScore
6.70
自引率
0.00%
发文量
47
审稿时长
3 months
期刊介绍: Free Radical Research publishes high-quality research papers, hypotheses and reviews in free radicals and other reactive species in biological, clinical, environmental and other systems; redox signalling; antioxidants, including diet-derived antioxidants and other relevant aspects of human nutrition; and oxidative damage, mechanisms and measurement.
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