Purposes: To assess the relationship between serum level of 25-hydroxyvitamin D (25(OH)D) and refractive error in Korean adolescents. Methods: A total of 2,038 adolescent aged 13-18 years, who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) from 2008 to 2011 underwent refractive examination using an autorefractor. Serum 25(OH)D concentration and other potential risk factors were examined. Multivariate regression analysis was performed to investigate the association between serum 25(OH)D and spherical equivalent (SE). Results: Among the participants, 80.1% had myopia (-0.5 D or more myopic) and 8.9% had high myopia (-6.0D or more myopia). The age-adjusted distribution of SE according to serum 25(OH)D concentration showed a positive relationship (r = 0.067, P = 0.012).The myopia group had a significant positive relationship between SE and serum 25(OH)D tertile concentration (P = 0.020), whereas the non-myopia group did not have any significant relationship (P = 0.599).In multiple linear regression analyses, SE was significantly associated with low serum 25(OH)D concentration after adjustment for area of residence, parental income, total energy intake, dietary Ca intake, milk consumption and smoking experience (P=0.047). The prevalence of high myopia was significantly associated with the lowest tertile of serum 25(OH)D concentration after adjustment for the confounding factors (P=0.017). Smoking experience showed inverse associations with both SE and the prevalence of high myopia (P = 0.001 and 0.036) Conclusions: Low serum 25(OH)D concentration was associated with myopia prevalence in Korean adolescents. This relationship was particularly notable in adolescents with high myopia.
Prolyl hydroxylase domain protein 2 (PHD2) belongs to an evolutionarily conserved superfamily of 2-oxoglutarate and Fe(II)-dependent dioxygenases that mediates homeostatic responses to oxygen deprivation by mediating hypoxia-inducible factor-1α (HIF-1α) hydroxylation and degradation. Although oxidative stress contributes to the inactivation of PHD2, the precise molecular mechanism of PHD2 inactivation independent of the levels of co-factors is not understood. Here, we identified disulfide bond-mediated PHD2 homo-dimer formation in response to oxidative stress caused by oxidizing agents and oncogenic H-rasV12 signalling. Cysteine residues in the double-stranded β-helix fold that constitutes the catalytic site of PHD isoforms appeared responsible for the oxidative dimerization. Furthermore, we demonstrated that disulfide bond-mediated PHD2 dimerization is associated with the stabilization and activation of HIF-1α under oxidative stress. Oncogenic H-rasV12 signalling facilitates the accumulation of HIF-1α in the nucleus and promotes aerobic glycolysis and lactate production. Moreover, oncogenic H-rasV12 does not trigger aerobic glycolysis in antioxidant-treated or PHD2 knocked-down cells, suggesting the participation of the ROS-mediated PHD2 inactivation in the oncogenic H-rasV12-mediated metabolic reprogramming. We provide here a better understanding of the mechanism by which disulfide bond-mediated PHD2 dimerization and inactivation result in the activation of HIF-1α and aerobic glycolysis in response to oxidative stress.
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