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

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.

Thyroid dysfunction, either hyper or hypothyroidism, promotes gallstone formation by different mechanisms.

We have investigated comprehensively the effects of thyroid function on gallstone formation in a mouse model. Gonadectomized gallstone-susceptible male C57BL/6 mice were randomly distributed into three groups each of which received an intervention to induce hyperthyroidism, hypothyroidism, or euthyroidism. After 5 weeks of feeding a lithogenic diet of 15% (w/w) butter fat, 1% (w/w) cholesterol, and 0.5% (w/w) cholic acid, mice were killed for further experiments. The incidence of cholesterol monohydrate crystal formation was 100% in mice with hyperthyroidism, 83% in hypothyroidism, and 33% in euthyroidism, the differences being statistically significant. Among the hepatic lithogenic genes, Trß was found to be up-regulated and Rxr down-regulated in the mice with hypothyroidism. In contrast, Lxrα, Rxr, and Cyp7α1 were up-regulated and Fxr down-regulated in the mice with hyperthyroidism. In conclusion, thyroid dysfunction, either hyperthyroidism or hypothyroidism, promotes the formation of cholesterol gallstones in C57BL/6 mice. Gene expression differences suggest that thyroid hormone disturbance leads to gallstone formation in different ways. Hyperthyroidism induces cholesterol gallstone formation by regulating expression of the hepatic nuclear receptor genes such as Lxrα and Rxr, which are significant in cholesterol metabolism pathways. However, hypothyroidism induces cholesterol gallstone formation by promoting cholesterol biosynthesis.