19 February 2018
Int J Med Sci 2017; 14(13):1335-1341. doi:10.7150/ijms.20653
HSPB8 Promotes the Fusion of Autophagosome and Lysosome during Autophagy in Diabetic Neurons
1. General Hospital of Ningxia Medical University, Yinchuan, 750000, China;
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.
Keywords: high glucose, autophagy, HSPB8, fusion.
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How to cite this article:
Li XC, Hu QK, Chen L, Liu Sy, Su S, Tao H, Zhang LN, Sun T, He LJ. HSPB8 Promotes the Fusion of Autophagosome and Lysosome during Autophagy in Diabetic Neurons. Int J Med Sci 2017; 14(13):1335-1341. doi:10.7150/ijms.20653. Available from http://www.medsci.org/v14p1335.htm