Reference - Detail
| RRC ID | 34911 |
|---|---|
| Author | Akiyama H, Kobayashi S, Hirabayashi Y, Murakami-Murofushi K. |
| Title | Cholesterol glucosylation is catalyzed by transglucosylation reaction of β-glucosidase 1. |
| Journal | Biochem Biophys Res Commun |
| Abstract |
Cholesteryl glucoside (β-ChlGlc), a monoglucosylated derivative of cholesterol, is involved in the regulation of heat shock responses. β-ChlGlc, which is rapidly induced in response to heat shock, activates heat shock transcription factor 1 (HSF1) leading to the expression of heat shock protein 70 (HSP70) in human fibroblasts. Identification and biochemical characterization of the enzyme responsible for β-ChlGlc formation is important for a complete understanding of the molecular mechanisms leading to HSP70-induction following heat shock. Recently, we demonstrated that β-ChlGlc synthesis is not dependent on UDP-Glucose but glucosylceramide (GlcCer) in animal tissue and human fibroblasts. In this study, we examined the possibility of glucocerebrosidase, a GlcCer-degrading glycosidase, acting as β-ChlGlc-synthesizing enzyme. Overexpression of β-glucosidase 1 (GBA1, lysosomal acid β-glucocerebrosidase) led to an increase in cholesterol glucosylation activity in human fibroblasts. Using a cell line generated from type 2 Gaucher disease patients with severe defects in GBA1 activity, we found that cholesterol glucosylation activity was very low in the cells and the overexpression of GBA1 rescued the activity. In addition, purified recombinant GBA1 exhibits conduritol B-epoxide-sensitive cholesterol glucosylation activity. The optimum pH and temperature for cholesterol glucosylation by GBA1 were at about 5.3 and 43 °C, respectively. Short chain C8:0-GlcCer was the most effective donor for cholesterol glucosylation activity among GlcCer containing saturated fatty acid (C8:0 to C18:0) tested. GlcCer containing mono-unsaturated fatty acid was more preferred substrate for cholesterol glucosylation when compared with GlcCer containing same chain length of saturated fatty acid. These results demonstrate, for the first time, a novel function of GBA1 as a β-ChlGlc-synthesizing enzyme. Therefore, our results also reveal a new pathway for glycolipid metabolism in mammals. |
| Volume | 441(4) |
| Pages | 838-43 |
| Published | 2013-11-29 |
| DOI | 10.1016/j.bbrc.2013.10.145 |
| PII | S0006-291X(13)01838-X |
| PMID | 24211208 |
| MeSH | Animals Catalysis Cell Line Cholesterol / analogs & derivatives* Cholesterol / biosynthesis Glucosylceramidase / genetics Glucosylceramidase / metabolism* Glycosylation Humans Mice beta-Glucosidase / genetics beta-Glucosidase / metabolism* |
| IF | 2.985 |
| Times Cited | 28 |
| WOS Category | BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
|
| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| DNA material | p3xFLAG-CMV-14_mGBA1 (RDB13236) p3xFLAG-CMV-14_mGBA2 (RDB13237) p3xFLAG-CMV-14_hGBA3tv1 (RDB13238) p3xFLAG-CMV-14_hGBA3tv2 (RDB13239) p3xFLAG-CMV-14_mLPH (RDB13240). |
| Human and Animal Cells | CHO-K1(RCB0285) |