Guanidine Hydrochloride Inhibits Hsp104 Activity In Vivo: A Possible Explanation for Its Effect in Curing Yeast Prions.

The presence of millimolar concentrations of guanidine hydrochloride (Gdn-HCl) in growth media causes efficient loss of the normally stable [PSI⁺] element from yeast cells. Although it has become common practice to include 5 mm Gdn-HCl in growth media to cure [PSI⁺] and other prions of yeast, the biochemical mechanism by which it cures is unknown. We find that 5 mm Gdn-HCl significantly reduces Hsp104-mediated basal and acquired thermotolerance. Gdn-HCl also reduced the ability of Hsp104 to restore activity of thermally denatured luciferase in vivo. The abundance of Hsp104 was not reduced in cells grown in the presence of Gdn-HCl, ruling out negative effects on expression or stability of Hsp104. We therefore conclude that Gdn-HCl inhibits Hsp104 activity in vivo. Since replication of yeast prions is dependent on Hsp104, our results suggest that Gdn-HCl cures prions by inhibiting Hsp104 activity. [ABSTRACT FROM AUTHOR]

Copyright of Current Microbiology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)