Glucose Oxidase- and UVA-Induced Changes in the Expression Patterns of Seven De-sumoylation Enzymes (SENPs) Are Associated with Cataract Development

Glucose Oxidase- and UVA-Induced Changes in the Expression Patterns of Seven De-sumoylation Enzymes (SENPs) Are Associated with Cataract Development
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葡萄糖氧化酶和 UVA 诱导的七种去素酰化酶 (SENP) 表达模式的变化与白内障的发生有关

DOI:
10.2174/1566524019666190311094313
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发表时间:
2019-01-01
影响因子:
2.5
通讯作者:
Li, David Wan-Cheng
Li, David Wan-Cheng
中科院分区:
医学4区
文献类型:
--
作者:
Xiang, Jia-Wen;Xiao, Yuan;Li, David Wan-Cheng

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目的:类小泛素化作为一种重要的调控机制,控制着许多不同的细胞过程。我们和其他人已经表明,类小泛素化在小鼠眼睛发育过程中起着不可或缺的作用。SUMO化是否参与眼部发病机制尚待进一步研究。在本研究中,我们已经研究了去类小泛素化酶(SENPs)的表达模式在体外白内障模型由葡萄糖氧化酶和UVA照射。从小鼠眼睛中小心地解剖出晶状体,并在M199培养基中培养12小时。选择透明晶状体(无手术损伤)进行实验。将晶状体暴露于UVA 60 min或用20 mU/mL葡萄糖氧化酶(GO)处理以诱导白内障形成。用qRT-PCR分析mRNA水平。结果:GO处理和UVA照射均可诱导体外培养的透镜形成白内障。GO处理显著下调SENP的mRNA水平,从50%至85%;另一方面,GO处理下7种SENP蛋白的表达出现在3种情况下:SENP 1、2和6上调; SENP 5和8下调; SENP 3和7不变。UVA照射上调所有7种SENP的mRNA水平;与7种SENP的mRNA水平相比,6种SENP的表达水平(SENP 1 -3、5-6和8)从10%下调至50%,并且仅SENP 7略微上调。我们的研究结果首次建立了GO或UVA处理下7种去类人猿化酶(SENP)的分化表达模式,其提供了将类泛素化与应激诱导的白内障发生联系起来的初步数据。
Objective: It has been well established that sumoylation acts as an important regulatory mechanism that controls many different cellular processes. We and others have shown that sumoylation plays an indispensable role during mouse eye development. Whether sumoylation is implicated in ocular pathogenesis remains to be further studied. In the present study, we have examined the expression patterns of the de-sumoylation enzymes (SENPs) in the in vitro cataract models induced by glucose oxidase and UVA irradiation.Methods: Four-week-old C57BL/6J mice were used in our experiments. Lenses were carefully dissected out from mouse eyes and cultured in M199 medium for 12 hours. Transparent lenses (without surgical damage) were selected for experimentation. The lenses were exposed to UVA for 60 min or treated with 20 mU/mL glucose oxidase (GO) to induce cataract formation. The mRNA levels were analyzed with qRT-PCR. The protein levels were determined with western blot analysis and quantitated with Image J.Results: GO treatment and UVA irradiation can induce cataract formation in lens cultured in vitro. GO treatment significantly down-regulated the mRNA levels for SENPs from 50% to 85%; on the other hand, expression of seven SENP proteins under GO treatment appeared in 3 situations: upregulation for SENP1, 2 and 6; downregulation for SENP 5 and 8; and unchanged for SENP3 and 7. UVA irradiation upregulates the mRNAs for all seven SENPs; In contrast to the mRNA levels for 7 SENPs, the expression levels for 6 SENPs (SENP1-3, 5-6 and 8) appeared down-regulated from 10% to 50%, and only SENP7 was slightly upregulated.Conclusion: Our results for the first time established the differentiation expression patterns of 7 de-sumoylation enzymes (SENPs) under treatment by GO or UVA, which provide preliminary data to link sumoylation to stress-induced cataractogenesis.