Molecular signature for senile and complicated cataracts derived from analysis of sumoylation enzymes and their substrates in human cataract lenses.
Molecular signature for senile and complicated cataracts derived from analysis of sumoylation enzymes and their substrates in human cataract lenses.
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通过分析人白内障晶状体中的苏酰化酶及其底物得出老年性和复杂性白内障的分子特征
作者：
Liu FY;Fu JL;Wang L;Nie Q;Luo Z;Hou M;Yang Y;Gong XD;Wang Y;Xiao Y;Xiang J;Hu X;Zhang L;Wu M;Chen W;Cheng B;Luo L;Zhang X;Liu X;Zheng D;Huang S;Liu Y;Li DW
类小泛素化是真核生物的重要调控机制之一。我们先前的研究揭示，类小泛素化在透镜分化过程中起着不可或缺的作用（Yan等人，2010.美国国家科学院院士107：21034-21039; Gong等人2014.美国国家科学院院士111：5574-5579）。sumoylation是否与白内障的发生有关，这是一种主要由衰老引起的疾病，仍然是一个谜。在本研究中，我们检测了50 - 90岁不同年龄组白内障晶状体中类小泛素化连接酶和去类小泛素化酶（SENP）及其底物（包括Pax 6和其他蛋白）的变化模式。结果发现，与正常晶状体相比，类小泛素化连接酶1和3、去类小泛素化酶SENP 3/7/8和p46 Pax 6明显增加。相反，Ubc 9显著降低。在50 ~ 70岁的白内障患者中，男性患者sumoylation酶和p46 Pax 6的表达明显高于女性患者。Ubc 9和SENP 6显示年龄依赖性增加。p46 Pax 6在正常透镜中表现出年龄依赖性降低，在老年性白内障中保持相对稳定，但在复杂性白内障中变得二小泛素化。相反，在老年性白内障中观察到p32 Pax 6的类小泛素化，并增加其稳定性。用氧化应激处理大鼠晶状体增加Pax 6表达，而不进行sumoylation，但促进细胞凋亡。因此，我们的研究结果表明，Ubc 9，SENP 6和Pax 6水平的变化模式可以作为老年性白内障的分子标志物，而二小泛素化的p46 Pax 6可以作为并发性白内障的分子标志物。总之，我们的研究结果揭示了老年性和复杂性白内障的分子特征的存在。此外，我们的研究表明，sumoylation涉及控制衰老和白内障。老年性白内障和并发性白内障的分子标记。类小泛素化连接酶Ubc 9和PIAS 1、去类小泛素化酶SENP 6的上调以及p32 Pax 6的SUMO 1结合是老年性白内障的分子标志物。p46 Pax 6的二小泛素化是并发性白内障的分子标志物。
Sumoylation is one of the key regulatory mechanisms in eukaryotes. Our previous studies reveal that sumoylation plays indispensable roles during lens differentiation (Yan et al. 2010. Proc Natl Acad Sci USA. 107:21034–21039; Gong et al. 2014. Proc Natl Acad Sci USA. 111:5574–5579). Whether sumoylation is implicated in cataractogenesis, a disease largely derived from aging, remains elusive. In the present study, we have examined the changing patterns of the sumoylation ligases and de‐sumoylation enzymes (SENPs) and their substrates including Pax6 and other proteins in cataractous lenses of different age groups from 50 to 90 years old. It is found that compared with normal lenses, sumoylation ligases 1 and 3, de‐sumoylation enzymes SENP3/7/8, and p46 Pax6 are clearly increased. In contrast, Ubc9 is significantly decreased. Among different cataract patients from 50s to 70s, male patients express more sumoylation enzymes and p46 Pax6. Ubc9 and SENP6 display age‐dependent increase. The p46 Pax6 displays age‐dependent decrease in normal lens, remains relatively stable in senile cataracts but becomes di‐sumoylated in complicated cataracts. In contrast, sumoylation of p32 Pax6 is observed in senile cataracts and increases its stability. Treatment of rat lenses with oxidative stress increases Pax6 expression without sumoylation but promotes apoptosis. Thus, our results show that the changing patterns in Ubc9, SENP6, and Pax6 levels can act as molecular markers for senile cataract and the di‐sumoylated p46 Pax6 for complicated cataract. Together, our results reveal the presence of molecular signature for both senile and complicated cataracts. Moreover, our study indicates that sumoylation is implicated in control of aging and cataractogenesis. The molecular signatures for both senile cataract and complicated cataract. Upregulation of sumoylation ligases Ubc9 and PIAS1, and de‐sumoylation enzyme SENP6, and SUMO1 conjugation of p32 Pax6 are molecular markers for senile cataract. Di‐sumoylation of p46 Pax6 is the molecular marker for complicated cataract.
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影响因子：
3.4
作者：
GARLAND, D
通讯作者：
GARLAND, D
饮食和内源性的小分子会影响透镜白内障的发作。
影响因子：
3.4
作者：
Barnes, Stephen;Quinlan, Roy A.
通讯作者：
Quinlan, Roy A.
BACE1 SUMO 化可提高其稳定性并增强阿尔茨海默病中的蛋白酶活性
DOI：
10.1073/pnas.1800498115
发表时间：
2018-04-10
影响因子：
11.1
作者：
Bao J;Qin M;Mahaman YAR;Zhang B;Huang F;Zeng K;Xia Y;Ke D;Wang Q;Liu R;Wang JZ;Ye K;Wang X
通讯作者：
Wang X
影响因子：
10.5
作者：
Groisman, Regina;Kuraoka, Isao;Nakatani, Yoshihiro
通讯作者：
Nakatani, Yoshihiro
影响因子：
5.3
作者：
CARRIERE, C;PLAZA, S;SAULE, S
通讯作者：
SAULE, S