REGULATION OF EXPRESSION OF THE GENE ENCODING HUMAN ACID BETA-GLUCOSIDASE IN DIFFERENT CELL-TYPES

Acid beta-glucosidase (betaGlc) activity and mRNA levels were measured in several human cell lines, and found to vary over 50-fold. A comparison between relative levels of betaGlc enzyme and mRNA levels revealed three patterns. The first group, including epithelial, lymphoblast, histiocyte, glioblastoma and astrocytoma cell lines. showed a direct relationship between relative levels of mRNA and enzyme activity, indicating that mRNA levels play an important role in determining enzyme activity. The second group, including fibroblast, promyelocyte and neuroglioma cell lines, also showed a direct relationship between betaGlc enzyme and mRNA levels within this group. but had enzyme activities that were approximately sixfold higher than expected, when compared with enzymes within the first group. The third pattern was exhibited by a single monocyte cell line, which showed high levels of betaGlc mRNA, but only intermediate levels of enzyme activity. These results suggest that although betaGlc mRNA levels play a major role in regulating betaGlc activity, other mechanisms also influence enzyme levels in certain cell lines. These results also demonstrate the importance of examining several different cell types when considering mechanisms of housekeeping gene regulation. Additionally. culturing cells in the presence of the betaGlc-specific inhibitor, conduritol-B-epoxide, did not affect betaGlc mRNA levels, and cells derived from normals had levels of betaGlc mRNA comparable to those from Gaucher disease patients. Thus, betaGlc mRNA levels are not subject to a mechanism of feedback regulation sensitive to the level of enzymatic activity in vitro, indicating that regulation of betaGlc mRNA levels is unlikely to explain the feedback regulation of betaGlc activity observed in vivo.