Resveratrol prevents hypoxia-induced retinal ganglion cell death related with ErbB2

白藜芦醇可预防缺氧引起的与 ErbB2 相关的视网膜神经节细胞死亡

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作者:Hyemin Seong, Joo Yeon Jeong, Jinhyun Ryu, Juyeong Park, Yong-Seop Han, Hyun-Kyung Cho, Seong Jae Kim, Jong Moon Park, Sang Soo Kang, Seong Wook Seo

Aim

To confirm the changes in proteins related with hypoxia-induced retinal cell death and to assess the effects of resveratrol (Res).

Conclusion

In light of Res favorable properties, it should be evaluated in the treatment of RGC death and related retinal disease characterized by ErbB2 and MDM2 expression. Therefore, Res is appropriate therapeutic agent for treating ischemic injury-related eye diseases by targeting the expression of ErbB2 and MDM2.

Methods

The therapeutic effect of Res was verified using an ischemic/reperfusion (I/R) model in vivo and a hypoxia modelin retinal ganglion cells (RGCs) in vitro. Death of RGCs were confirmed by TUNEL assay. Protein expression was confirmed by Western blotting and immunohistochemistry. In addition, flow cytometric analysis was used to confirm the response in the cell unit to obtain more accurate data.

Results

ErbB2 expression and apoptosis in the ganglion cell layer (GCL) increased after I/R injury. Treatment of Res rescued I/R-induced ganglion cell death, downregulated apoptosis and ErbB2 protein expression in the retina. In subsequent in vitro models, Res affects apoptosis by regulating the phosphorylation and expression of mouse double minute 2 homolog (MDM2), along with those of ErbB2. These results suggest that Res reverses GCL-specific apoptosis via downregulation of ErbB2 in ischemic injury.

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