Please use this identifier to cite or link to this item:
標題: 類固醇藥物對於同半胱胺酸代謝的影響
Effects of glucocorticoids on homocysteine metabolism
作者: 葉麗冰
Yep, Lai-Ping
關鍵字: glucocorticoid;類固醇藥物;homocysteine;同半胱胺酸
出版社: 食品暨應用生物科技學系
結果發現 prednisolone 不影響甲硫胺酸負荷前和負荷後同半胱胺酸的濃度,但增加甲硫胺酸負荷後胱胺酸的濃度。Prednisolone增加了非肝組織的轉硫作用。我們發現prednisolone不影響腎臟中腺苷甲硫胺酸的合成、去氧核糖核酸甲基轉移酶活性。但是prednisolone卻特異性的抑制了肝臟中同半胱胺酸再甲基化、腺苷甲硫胺酸的合成以及去氧核糖核酸甲基轉移酶活性。肝臟中低濃度的腺苷甲硫胺酸與減少甲基化的程度相關。因此長期服用prednisolone可能會造成表觀遺傳調控的基因表現改變或增加基因不完整性的風險。至於長期服用prednisolone對於動物體內甲基化的影響則將在未來的研究中予以深入探討。

Background. Glucocorticoids such as prednisolone are potent and commonly used anti-inflammatory agents for the clinical treatment of human rheumatoid arthritis, asthma, and even in HIV-1-infected patients with severe pneumocystis pneumonia. In the literature, much remains to be clarified regarding the inconsistencies of the role of glucocorticoids on the metabolism of homocysteine. The present study was conducted to systematically investigate the effects of long-term prednisolone treatment on the regulation of one carbon metabolism and homocysteine kinetics in vivo.
Methods. After intraperitoneal injection of prednisolone to mice for 4 weeks, a methionine loading test was performed to investigate the impacts of prednisolone on homocysteine transsulfuration. AdoMet, adoHcy, homocysteine, and the impacts of prednisolone on DNA methyltransferase were determined. Genes participating the methylation cycle were examined. We also investigated the in vivo effects of prednisolone treatment on homocysteine metabolic fluxes in remethylation, transmethylation and transsulfuration using stable isotopic tracers.
Results. Prednisolone treatment increased post-methionine load cysteine without affecting fasting or post- methionine load homocysteine. Prednisolone increased transsulfuration flux in extra-hepatic tissues but not in liver. On the other hand, prednisolone did not alter adoMet synthesis or DNA methyltransferase activity in kidney. Finally, prednisolone treatment specifically inhibited hepatic homocysteine remethylation, reduced hepatic adoMet syntheisis, and inhibited DNA methyltransferase activity.
Conclusion. In the present study we demonstrated the novel findings that prednisolone specifically inhibited hepatic adoMet synthesis and DNA methyltransferase. Reduced adoMet synthesis has been related to impaired capacity for methylation, and our study may also suggest that long-term prednisolone treatment may have epigenetic alterations in gene expression or may affect genomic integrity I humans. Future studies on the long-tern effects of prednisolone treatment on in vivo methylation reactions are warranted.
Appears in Collections:食品暨應用生物科技學系

Show full item record

Google ScholarTM


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.