肝臓星細胞に発現するビタミンA貯蔵酵素lecithin:retinol acyltransferaseによる血中レチノール濃度の調節 : 還流培養系での代謝シミュレーション

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Lecithin:retinol acyltransferase (LRAT) is mainly expressed in hepatic stellate cells (HSC) in the liver. In the present study, we simulated whether LRAT in HSC controlled a blood retinol level using the metabolic perfusion culture model. The medium with retinol closely circulated through LRAT-expressing cells or vehicle cells cultured in the bioreactor. Culture medium was sampled to measure retinol level. A three compartment model was built using an interactive computer program SAAMII to determine metabolic parameters of retinol in the bioreactor system. The compartments comprised 3 metabolically distinct pools for retinol; reservoir, reactor, and cultured cells. LRAT catalyzing the esterification of retinol was added as an element of the retinol metabolic route in LRAT-expressing cells except a metabolic route (mainly oxidization) in vehicle cells. We succeeded in matching the retinol fate curve, which was depicted on the plots of retinol levels actually measured. The retinol kinetics curve determined in the circulation medium cultured with LRAT-expressing cells showed a lower level of retinol when compared with vehicle cells. The rate constant for the change of retinol into other metabolites calculated by SAAMII proved that LRAT contributed to about half of the metabolism of retinol in cells. Indeed, high levels of retinyl esters were detected in LRAT-expressing cells in the bioreactor. This simulation suggests that LRAT expressed in HSC in the liver contributes to regulation of blood retinol level.
2012-08-25

肝臓星細胞に発現するビタミンA貯蔵酵素lecithin:retinol acyltransferaseによる血中レチノール濃度の調節 : 還流培養系での代謝シミュレーション

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