Oxidative Stress Stimulates Autophagic Flux During Ischemia/Reperfusion
Oxidative Stress Stimulates Autophagic Flux During Ischemia/Reperfusion
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DOI：
10.1089/ars.2010.3488
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发表时间：
2011-06-01
影响因子：
6.6
通讯作者：
Sadoshima, Junichi
中科院分区：
文献类型：
--
作者：
Hariharan, Nirmala;Zhai, Peiyong;Sadoshima, Junichi
自噬是一个整体降解过程，其中细胞溶质蛋白和细胞器通过溶酶体降解。为了评估心肌细胞中的自噬通量，我们产生了携带串联荧光mRFP-GFP-LC 3的腺病毒和心脏特异性转基因小鼠。饥饿显著增加了mRFP-GFP-LC 3点的数量，这些点代表每个细胞的自噬体和自溶酶体，表明心肌细胞中的自噬通量增加。H2 O2显着增加自噬通量，这是衰减的N-2-巯基丙酰甘氨酸（MPG），抗氧化剂的存在下，表明氧化应激刺激心肌细胞自噬。心肌缺血/再灌注（I/R）增加自噬体和自溶酶体，从而增加自噬流量。MPG治疗减弱了I/R诱导的氧化应激、自噬通量和Beclin-1表达的增加，伴随着心肌梗死（MI）/危险区（AAR）的缩小，表明氧化应激在I/R期间介导自噬和心肌损伤中起重要作用。在beclin 1（+/-）小鼠中，I/R后MI/AAR显著减少，而用MPG处理的beclin 1（+/-）小鼠在I/R后MI/AAR的大小没有进一步减少。这些结果表明，氧化应激在介导I/R期间的自噬中起着重要作用，并且通过氧化应激激活自噬介导小鼠心脏中响应于I/R的心肌损伤。抗氧化剂。氧化还原信号。14，2179-2190。
Autophagy is a bulk degradation process in which cytosolic proteins and organelles are degraded through lysosomes. To evaluate autophagic flux in cardiac myocytes, we generated adenovirus and cardiac-specific transgenic mice harboring tandem fluorescent mRFP-GFP-LC3. Starvation significantly increased the number of mRFP-GFP-LC3 dots representing both autophagosomes and autolysosomes per cell, suggesting that autophagic flux is increased in cardiac myocytes. H2O2 significantly increased autophagic flux, which was attenuated in the presence of N-2-mercaptopropionyl glycine (MPG), an antioxidant, suggesting that oxidative stress stimulates autophagy in cardiac myocytes. Myocardial ischemia/reperfusion (I/R) increased both autophagosomes and autolysosomes, thereby increasing autophagic flux. Treatment with MPG attenuated I/R-induced increases in oxidative stress, autophagic flux, and Beclin-1 expression, accompanied by a decrease in the size of myocardial infarction (MI)/area at risk (AAR), suggesting that oxidative stress plays an important role in mediating autophagy and myocardial injury during I/R. MI/AAR after I/R was significantly reduced in beclin1(+/-) mice, whereas beclin1(+/-) mice treated with MPG exhibited no additional reduction in the size of MI/AAR after I/R. These results suggest that oxidative stress plays an important role in mediating autophagy during I/R, and that activation of autophagy through oxidative stress mediates myocardial injury in response to I/R in the mouse heart. Antioxid. Redox Signal. 14, 2179-2190.