Modulation of cellular glycosidase activity by hyperthermia

Abstract

We examined the effect of 45°C hyperthermia on the following glycosidases in CHO cells: β-galactosidase, β-hexosaminidase, β-glucuronidase and α-mannosidase. Among these, lysosomal α-mannosidase exhibited the most dramatic response to hyperthermia with an increase in activity immediately after 45°C hyperthermia. The increase was linearly dose-dependent with a doubling of activity for every 20 min at 45°C. In contrast to α-mannosidase, β-glucuronidase, β-galactosidase, and β-hexosaminidase showed only minor alterations in activity, or none, after hyperthermia of 10 to 60 min at 45°C. Induction of thermotolerance enhanced the heat resistance of β-galactosidase, but caused increased heat sensitivity for α-mannosidase. Intracellular β-galactosidase, measured by histochemical staining, showed a dramatic redistribution in response to mild hyperthermia (10 min, 45°C); the same effect was not observed for β-glucuronidase. The data argue against non-specific activation of lysosomes by hyperthermia, and suggest that cells contain lysosomal subpopulations that are characterized by different heat sensitivities and variable glycosidase contents.

Key Words:

• Hyperthermia
• thermotolerance
• glycosidase
• glucuronidase
• tumour targeting