Catalase ameliorates diabetes-induced cardiac injury through reduced p65/RelA- mediated transcription of BECN1.
Catalase ameliorates diabetes-induced cardiac injury through reduced p65/RelA- mediated transcription of BECN1.
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过氧化氢酶通过减少 p65/RelA 介导的 BECN1 转录来改善糖尿病引起的心脏损伤
DOI：
10.1111/jcmm.13252
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发表时间：
2017-12
影响因子：
5.3
通讯作者：
Jin L
中科院分区：
文献类型：
--
作者：
Wang X;Tao Y;Huang Y;Zhan K;Xue M;Wang Y;Ruan D;Liang Y;Huang X;Lin J;Chen Z;Lv L;Li S;Chen G;Wang Y;Chen R;Cong W;Jin L
过氧化氢酶是一种抗氧化酶，它将超氧化物歧化酶产生的过氧化氢(H_2O_2)从高活性的超氧化物(O_2·−)转化为水和氧分子。尽管最近的研究表明过氧化氢酶、自噬和核因子κB(NF-κB)信号通路在糖尿病心肌病中起中心作用，但三者之间的相互作用还没有得到充分的表征。因此，本研究探讨了过氧化氢酶对糖尿病小鼠心脏损伤的保护作用机制，并探讨了核因子-κB-p65在自噬通量调节中的作用。Western印迹分析显示，过氧化氢酶抑制NF-κB活性，降低微管相关蛋白1轻链3(MAP1轻链3)和Beclin-1(ATG6)的表达。此外，自噬的上调对糖尿病小鼠的心脏功能是有害的。过氧化氢酶的过度表达降低了细胞核中的NF-κB亚单位的水平，在那里它通过激活关键的自噬基因BECN1来启动自噬。为了探讨核因子-κB途径在糖尿病自噬中的作用，将核因子-κB抑制剂BA117082注射到糖尿病小鼠体内，抑制了核因子-κB，减轻了糖尿病诱导的自噬和心肌细胞凋亡。与体内实验结果一致，BA117082还可抑制高糖诱导的H9c2细胞中NF-κB的激活以及Lc3-II和BECLIN-1表达的上调。此外，高糖诱导的自噬通量的激活和凋亡在很大程度上被p65siRNA减弱，这表明过氧化氢酶改善了糖尿病诱导的自噬，至少部分是通过增加NF-κB途径的活性和p65介导的BECN1的转录。
Catalase is an antioxidative enzyme that converts hydrogen peroxide (H2O2) produced by superoxide dismutase from highly reactive superoxide (O2 −) to water and oxygen molecules. Although recent findings demonstrate that catalase, autophagy and the nuclear factor κB (NF‐κB) signalling pathway are centrally involved in diabetic cardiomyopathy (DCM), the interplay between the three has not been fully characterized. Thus, the mechanism responsible for catalase‐mediated protection against heart injury in diabetic mice was investigated in this study, as well as the role of NF‐κB‐p65 in the regulation of autophagic flux was investigated in this study. Western blot analysis revealed that catalase inhibited NF‐κB activity and decreased LC3‐II (microtubule‐associated protein 1 light chain 3) and beclin‐1 (Atg6) expression. Furthermore, up‐regulation of autophagy was detrimental for cardiac function in diabetic mice. Catalase overexpression reduced the level of NF‐κB subunit in the nucleus, where it initiates autophagy through activation of the key autophagy gene BECN1. To evaluate the role of the NF‐κB pathway in diabetes‐induced autophagy, Bay11‐7082, an NF‐κB inhibitor, was injected into diabetic mice, which suppressed NF‐κB and attenuated diabetes‐induced autophagy and myocardial apoptosis. In agreement with the in vivo results, Bay11‐7082 also inhibited high‐glucose‐induced activation of NF‐κB and the up‐regulation of LC3‐II and beclin‐1 expression in H9c2 cells. In addition, high‐glucose‐induced activation of autophagic flux and apoptosis were largely attenuated by p65 siRNA, suggesting that catalase ameliorates diabetes‐induced autophagy, at least in part by increasing the activity of the NF‐κB pathway and p65‐mediated transcription of BECN1.
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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
7.7
作者：
Bhatt MP;Lim YC;Kim YM;Ha KS
通讯作者：
Ha KS
DOI：
10.1016/j.bbadis.2014.06.030
发表时间：
2015-02
影响因子：
6.2
作者：
Varga, Zoltan V.;Giricz, Zoltan;Liaudet, Lucas;Hasko, Gyoergy;Ferdinandy, Peter;Pacher, Pal
通讯作者：
Pacher, Pal
DOI：
10.1152/ajpendo.00176.2012
发表时间：
2013-01-01
影响因子：
5.1
作者：
Jiang, Shasha;Guo, Rui;Ren, Jun
通讯作者：
Ren, Jun
影响因子：
13.3
作者：
Ma, Xiucui;Godar, Rebecca J.;Diwan, Abhinav
通讯作者：
Diwan, Abhinav