Bioconversion of Corticosterone into Corticosterone-Glucoside by Glucosyltransferase

Abstract

Glucosylation of the 21-hydroxyl group of glucocorticoid changes its solubility into hydrophilicity from hydrophobicity and, as with glucocorticoid glucuronides as a moving object in vivo, it is conceivable that it exhibits the same behavior. Therefore, glucosylation to the 21-hydroxyl group while maintaining the 11β-hydroxyl group is particularly important, and glucosylation of corticosterone was confirmed by high-resolution mass spectrometry and 1D (1H and 13C) and 2D (COSY, ROESY, HSQC-DEPT and HMBC) NMR. Moreover, the difference in bioactivity between corticosterone and corticosterone 21-glucoside was investigated in vitro. Corticosterone 21-glucoside showed greater neuroprotective effects against H2O2-induced cell death and reactive oxygen species (ROS) compared with corticosterone. These results for the first time demonstrate that bioconversion of corticosterone through the region-selective glucosylation of a novel compound can present structural potential for developing new neuroprotective agents.

Development of a miniaturized 96-Transwell air–liquid interface human small airway epithelial model

“…Increased levels of TNF-α have been found in the lungs of IPF patients and in animal models for pulmonary fibrosis. Previously, 10 ng/mL of TNF-α had been observed to lower the TEER value across a confluent layer of ALI-conditioned A549 cells 37 . Similar to this dose effect, TNF-α reduced the electric resistance across a layer of ALI-cultured hSAE cells with a mean EC50 value of 16, 95% CI = [10, 25] ng/mL.…”

“…TNF-α had earlier been recognized to stimulate nuclear factor kappa B (NF-κB)-mediated signaling 37 . In accordance with the involvement of this signaling chain in the TNF-α-driven activation of airway epithelium, the small molecule inhibitor of IκB ubiquitination Ro 106-9920 29 decreased the secretion of MMP9 and MCP-1 from TNF-α–stimulated hSAE cells with mean IC50 values of 0.75, 95% CI = [0.55, 1.2] µM and 1.5; 95% CI = [0.97, 4.6] µM, respectively.…”

Enzymatic Synthesis of Anabolic Steroid Glycosides by Glucosyltransferase from Terribacillus sp. PAMC 23288

“…2 ). The UGT-1 investigated herein should react not only with known steroids [ 28 ] but also with flavonoid substrates that react with YjiC because of its high identity with YjiC [ 35 ].…”

“…Corticosterone is glucosylated by UGT-1, which attaches a sugar to C21 [ 28 ]. Sugars are attached to testosterone, nandrolone, cortisone, and prednisone at terminal hydroxyl groups.…”

“…Lipophilic steroids, such as steroid ester derivatives, have been studied in detail; in contrast, studies on hydrophilic steroids are scant. Hydrophilic steroids can be prepared by glycosylation [ 28 ], but the yield of conventionally prepared glycosylated products is insufficient and the process is complicated [ 29 , 30 ]. In addition, investigations into steroid glycosylation might have been avoided because testosterone glycosides have considerably lower local bioactivity than the ester forms [ 31 - 33 ].…”