High glucose upregulates CYP24A1 expression which attenuates the ability of 1,25(OH)(2)D-3 to increase NGF secretion in a rat Schwann cell line RSC96

摘要

Vitamin D deficiency or insufficiency is an independent risk factor for diabetic peripheral neuropathy (DPN), but the relationship between 1,25(OH)(2)D-3 and DPN remains unknown. We found that 1,25(OH)(2)D-3 stimulated the secretion of nerve growth factor (NGF) in rat Schwann cell line RSC96, but ability of 1,25(OH)(2)D-3 to increase NGF protein was impaired under high glucose conditions. High glucose upregulated the expression of CYP24A1 protein, which catalyzes the conversion of 1,25(OH)(2)D-3 into inactive products, further impairing the ability of 1,25(OH)(2)D-3 to upregulate NGF secretion in Schwann cells. Inhibition of CYP24A1 protein expression ameliorated the secretion of NGF in response to 1,25(OH)(2)D-3. The findings of this study suggest that CYP24A1 protein plays an important role in the relationship between DPN and 1,25(OH)(2)D-3. (C) 2015 Published by Elsevier Ireland Ltd.