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Fan X.,Case Western Reserve University | Zhou S.,Sun Yat Sen University | Wang B.,Case Western Reserve University | Hom G.,Fairview High School | And 5 more authors.
Molecular and Cellular Proteomics | Year: 2015

Low glutathione levels are associated with crystallin oxidation in age-related nuclear cataract. To understand the role of cysteine residue oxidation, we used the novel approach of comparing human cataracts with glutathionedepleted LEGSKO mouse lenses for intra- versus intermolecular disulfide crosslinks using 2D-PAGE and proteomics, and then systematically identified in vivo and in vitro all disulfide forming sites using ICAT labeling method coupled with proteomics. Crystallins rich in intramolecular disulfides were abundant at young age in human and WT mouse lens but shifted to multimeric intermolecular disulfides at older age. The shift was 4x accelerated in LEGSKO lens. Most cysteine disulfides in β-crystallins (except βA4 in human) were highly conserved in mouse and human and could be generated by oxidation with H2O2, whereas γ-crystallin oxidation selectively affected γC23/42/79/80/154, γD42/33, and γS83/115/130 in human cataracts, and γB79/80/110, γD19/109, γF19/79, γE19, γS83/130, and γN26/128 in mouse. Analysis based on available crystal structure suggests that conformational changes are needed to expose Cys42, Cys79/80, Cys154 in γC; Cys42, Cys33 in γD, and Cys83, Cys115, and Cys130 in γS. In conclusion, the β-crystallin disulfidome is highly conserved in age-related nuclear cataract and LEGSKO mouse, and reproducible by in vitro oxidation, whereas some of the disulfide formation sites in γ-crystallins necessitate prior conformational changes. Overall, the LEGSKO mouse model is closely reminiscent of agerelated nuclear cataract. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Source


Huang S.-X.,Peoples Hospital of Hainan Province | Zhao Z.-Y.,Peoples Hospital of Hainan Province | Weng G.-H.,Peoples Hospital of Hainan Province | He X.-Y.,Peoples Hospital of Hainan Province | And 5 more authors.
International Journal of Oncology | Year: 2016

To investigate the expression and clinical significance of miR-181a and its target genes in glioblastoma multiforme (GBM), the expression levels of miR-181a and three target genes in human normal brain tissues and GBM were analyzed in silico using gene microarray, gene ontology, KEGG pathway and hierarchical clustering analysis followed by validation with quantitative RT-PCR. Our results show that miR-181a is down-regulated in GBM patients. The three target genes, ANGPT2, ARHGAP18 and LAMC1, are negatively correlated with the expression of miR-181a. Moreover, high expression of ANGPT2 or LAMC1 together with large size of GBM is correlated with a shorter median overall survival. In conclusion, our results showed that miR-181a and it targets ANGPT2 and LAMC1 might be predictors of prognosis in GBM patients. Source

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