Lovastatin increases RhoA level and megalin-mediated endocytosis of serum-derived bovine serum albumin in cultured cortical astrocytes
| Autor: | Jian-Lin Li, 李建霖 |
|---|---|
| Rok vydání: | 2013 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 101 Statins, which are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, reduce both cholesterol and isoprenoid synthesis and have been used to treat patients with diseases associated with hypercholesterolemia. Moreover, previous studies have demonstrated their therapeutical effectiveness in some, but not all, patients suffering Alzheimer’s disease. Previous studies from this laboratory have demonstrated that lovastain increases cellular levels of RhoA and serum-derived bovine serum albumin (BSA) in astrocytes, but not in neurons. This study thus aims to explore the mechanism(s) by which lovastatin modulates RhoA expression and albumin endocytosis in astrocytes. In this study, we found that lovastatin increases the cellular content of serum-derived bovine serum albumin (BSA) in cortical astrocytes. Immunoprecipitation and immunocytochemical studies reveal that lovastatin treatment increases the interaction of BSA with megalin, an endocytic receptor for multiple ligands including albumin. In addition, lovastatin increase the internalization of biotin-labeled surface proteins and the cellular content of BSA after BSA challenge. Interestingly, elevated level of RhoA was observed in astrocytes treated with lovastatin for 24 hr when the cellular BSA content was not affected. The effect of lovastatin on BSA, in fact, became apparent at a later time point, 48 hr. As noted, it was also found that lovastatin caused accumulation of ubiquitin-labeled proteins in a temporal profile similar to the increase in RhoA content. Moreover, mevalonate prevented lovastatin from increasing both RhoA and ubiquitin-labeled proteins. However, lovastatin didn’t decrease chymotrypsin-like proteasome activity. Together, results from this work demonstrate the involvement of ubiquitin and megalin in elevated levels of RhoA and internalized BSA, respectively, in astrocytes exposed to lovasatin. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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