| First Author | Huang Y | Year | 2021 |
| Journal | Biochem Biophys Res Commun | Volume | 537 |
| Pages | 43-49 | PubMed ID | 33383563 |
| Mgi Jnum | J:305694 | Mgi Id | MGI:6705274 |
| Doi | 10.1016/j.bbrc.2020.12.071 | Citation | Huang Y, et al. (2021) Cataract formation in transgenic HO-1 G143H mutant mice: Involvement of oxidative stress and endoplasmic reticulum stress. Biochem Biophys Res Commun 537:43-49 |
| abstractText | Oxidative stress and endoplasmic reticulum (ER) stress are the key contributing factors for cataract progression. In our previous studies, we demonstrated that the nuclear factor erythroid 2-like-2 (Nrf-2)/heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis protects lens epithelial cells (LECs) against oxidants and ER stress. In the present study, transgenic FVB/N mice overexpressing the negative dominant mutant HO-1 G143H (TgHO-1 G143H) were generated to evaluate the crosstalk among HO-1, oxidative stress and ER stress in maintaining lens transparency. Slit-lamp examination revealed that nuclear cataracts occurred at 4 months in the TgHO-1 G143H mice, which was 5 months earlier than that of the control mice. The lenses of the transgenic mice showed an accumulation of malondialdehyde and protein carbonyl with a decrease in glutathione and protein sulfhydryl levels. Elevated concentrations of ER stress biomarkers (Bip, PERK, ATF6, IRE1, CHOP, caspase-12 and caspase-3) in the lenses of the TgHO-1 G143H mice were identified by western blotting. Furthermore, we confirmed that overexpressed HO-1 G143H in LECs resulted in oxidative insult and apoptosis in vitro. All of these data suggested that HO-1 enzymatic activity loss induces early-onset nuclear cataracts by activating oxidative stress and ER stress. |
