HSPB8 Promotes the Fusion of Autophagosome and Lysosome during Autophagy in Diabetic Neurons.
HSPB8 Promotes the Fusion of Autophagosome and Lysosome during Autophagy in Diabetic Neurons.
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HSPB8 促进糖尿病神经元自噬过程中自噬体和溶酶体的融合
DOI：
10.7150/ijms.20653
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发表时间：
2017
影响因子：
3.6
通讯作者：
He LJ
中科院分区：
文献类型：
--
作者：
Li XC;Hu QK;Chen L;Liu SY;Su S;Tao H;Zhang LN;Sun T;He LJ
虽然自噬已被提出在糖尿病神经病变中发挥新的作用，但自噬及其可能的作用仍不清楚。此外，只有少数关于糖尿病的研究探讨了热休克蛋白β 8（HSPB 8）和Bcl-2相关的凋亡基因3（BAG 3）介导的自噬。在本研究中，我们研究了在体内糖尿病大鼠模型链脲佐菌素（STZ）和视网膜神经节细胞-5（RGC 5）细胞在高糖条件下的体外模型中，高糖水平诱导的自噬。在STZ诱导的糖尿病大鼠的脊髓组织中，轻链3（LC 3）和Beclin-1标记的自噬水平随着HSPB 8和BAG 3水平的增加而升高。通过共聚焦免疫荧光，观察到HSPB 8和LC 3在脊髓组织中共定位。高糖刺激可上调RGC 5细胞中LC 3-Ⅱ、Beclin-1和HSPB 8的表达，且呈剂量依赖性。高糖条件下，HSPB 8过表达沿着LC 3-Ⅱ和Beclin-1表达上调，自噬率增加，而siRNA沉默HSPB 8则降低自噬率。此外，在GFP-mRFP-LC 3探针实验中，HSPB 8过表达促进了自噬体-溶酶体融合，而HSPB 8沉默破坏了这一过程。在用HSPB 8和siRNA处理的细胞中，融合受损，如升高的p62表达所示。HSPB 8过表达可通过降低p62的表达水平部分缓解氯喹对自噬流的阻断作用。我们的研究表明，HSPB 8参与了体内和体外条件下高糖诱导的自噬，并在自噬流中关键性地参与了自噬体-溶酶体融合。
Although autophagy has been proposed to play an emerging role in diabetic neuropathy, autophagy and its possible role remains unclear. Moreover, only few studies about diabetes have explored the autophagy mediated by heat shock protein beta-8 (HSPB8) and Bcl-2 associated athanogene 3 (BAG3). In the present study, we examined the autophagy induced by high glucose levels in an in vivo rat model of diabetes induced by streptozotocin (STZ) and an in vitro model of retinal ganglion cell-5 (RGC5) cells under high glucose conditions. In the spinal cord tissues of the STZ-induced diabetic rats, the levels of light chain 3 (LC3) and Beclin-1-marked autophagy rose with increasing HSPB8 and BAG3 levels. By confocal immunofluorescence, HSPB8 and LC3 were observed to be co-localized in the spinal cord tissues. In the RGC5 cells, high-glucose stimulation upregulated the expression of LC3-Ⅱ, Beclin-1, and HSPB8 in a dose-dependent manner. When the RGC5 cells were subjected to high-glucose conditions, HSPB8 overexpression, along with upregulated LC3-Ⅱ and Beclin-1 expression, increased the autophagic rate, whereas siRNA-silenced HSPB8 decreased the autophagic rate. Furthermore, in GFP-mRFP-LC3 probe experiments, HSPB8 overexpression promoted autophagosome-lysosome fusion, whereas HSPB8 silencing disrupted this process. In the cells treated with HSPB8 and siRNA, the fusion was impaired, as indicated by the elevated p62 expression. HSPB8 overexpression can partly rescue the blocking of the autophagy flux with chloroquine through the reduction of p62 expression level. Our study demonstrated that HSPB8 is involved in the high glucose-induced autophagy under the in vivo and in vitro conditions and critically participated in the autophagosome-lysosome fusion during the autophagy flux.
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影响因子：
8
作者：
Inomata, Megumi;Niida, Shumpei;Shibata, Ken-ichiro;Into, Takeshi
通讯作者：
Into, Takeshi
镉通过抑制原代大鼠近端肾小管细胞中胞浆 Ca2 依赖性自噬体-溶酶体融合来破坏自噬通量
影响因子：
4.5
作者：
Liu, Fei;Wang, Xin-Yu;Wang, Lin
通讯作者：
Wang, Lin
影响因子：
13.3
作者：
Gurusamy, Narasimman;Lekli, Istyan;Das, Dipak K.
通讯作者：
Das, Dipak K.
DOI：
10.12659/msm.897379
发表时间：
2016-03-24
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Ma Y;Gai Y;Yan J;Li J;Zhang Y
通讯作者：
Zhang Y
影响因子：
--
作者：
Talaei F;Van Praag VM;Shishavan MH;Landheer SW;Buikema H;Henning RH
通讯作者：
Henning RH