SMP30 May protect human lens epithelial cells against high glucose-induced oxidative damage by regulating the Keap1/Nrf2/NQO1 pathway.

The aim of this study was to explore the role and mechanism of SMP30 in diabetic cataract(DC) patients with different glycemic control levels and high glucose-stimulated human lens epithelial cells. First, aqueous humor and lens anterior capsules were collected during cataract surgery. Second, human lens epithelial B3(HLE-B3) cells were stimulated with different glucose concentrations. Then, SMP30-overexpressing plasmids were transfected into HLE-B3 cells. Measured blood and aqueous humor glucose concentrations in cataract patients. Oxidative stress levels was assessed by analyzing SOD, MDA and ROS. The mRNA and protein expression levels of SMP30 and Keap1/Nrf2/NQO1 pathway factors were detected. The cell viability was analyzed. The glucose concentration in blood and aqueous humor increased, and MDA content increased and SOD activity decreased in DC patients with poor glycemia control. However, SMP30 expression was upregulated of these patients, in parallel with the possible activation of Keap1/Nrf2/NQO1 pathway. The MDA content and ROS levels increased, and SOD activity decreased under high glucose(40 mM, 60 mM) in HLE-B3 cells. Meanwhile, SMP30 expression was up-regulated and Keap1/Nrf2/NQO1 pathway was activated at a glucose of 20 mM, but down-regulated and Keap1/Nrf2/NQO1 pathway was inhibited at a glucose of 40 mM or 60 mM. Overexpression of SMP30 reduced the oxidative stress damage and increased the cell viability, and reversed the expression of Keap1/Nrf2/NQO1 pathway factors induced by high glucose in HLE-B3. This study demonstrates that SMP30 may protect human lens epithelial cells from high glucose-stimulated oxidative stress damage and may involves the regulation of Keap1/Nrf2/NQO1 pathway.