Biliverdin Reductase A Protects Lens Epithelial Cells against Oxidative Damage and Cellular Senescence in Age-Related Cataract

Figure 9

The effect of BVRA on preventing cellular senescence against oxidative stress in LECs. Cellular senescence, an important risk factor for ARC formation, is closely associated with redox imbalance in LECs. Cataractogenic stresses give rise to intracellular ROS accumulation, antioxidant depletion, and cell aging in LECs. To prevent cellular senescence against oxidative stress, the BVRA-mediated antioxidative defense system takes effect in three manners. First, BVRA protects LECs from mitochondrial dysfunction and eliminates ROS in a BR-dependent manner by converting BV into BR. Second, enhanced nuclear trafficking of BVRA directly promotes HO-1 expression upon oxidation. Third, BVRA activates ERK/Nrf2 signaling by promoting phosphorylation of ERK1/2 and Nrf2 nuclear localization. However, the antioxidative effect of BVRA was diminished in senescent LECs, which would be resulted from the decreased enzymatic activity of BVRA and the repressed nucleocytoplasmic trafficking.