A subset of histamine receptor ligands improve thermotolerance of the yeast Saccharomyces cerevisiae

Abstract

Aims: Histamine interacts with the stress response in eukaryotes. This study investigated the effects of antihistamines on the heat shock (HS) response in yeast, thereby exploring their functions in a well-established histamine receptor (H x R)-free model. Methods and Results: Stress response was evaluated by determining growth and viability of postlogarithmic phase grown yeast cultures after HS at 53°C for 30 min. The effects of H x R ligands were investigated following short-and long-term administration. The H 1 R antagonist dimethindene exerted doserelated antifungal actions, whereas the H 2 R antagonist ranitidine failed to elicit any effect. In contrast, the H 3/4 R and H 4 R ligands, thioperamide and JNJ7777120, respectively, induced the thermotolerant phenotype. The circumvention of thermotolerance by cycloheximide and the induction of Hsp70 and Hsp104 expression indicated the contribution of de novo protein synthesis in the adaptive process, likely directed towards alterations in Hsp expression. Conclusions: The data provide evidence for the differential function of H x R ligands in thermotolerance induction in yeast. Significance and Impact of the Study: First demonstration of the action of antihistamines in the HS response in yeast. The work supports the potential H x R-independent functions of histaminergic compounds in fungal adaptation and stimulates research on the prospect of their exploitation in eukaryotic (patho)physiology.

Anti-prion Drugs Targeting the Protein Folding Activity of the Ribosome Reduce PABPN1 Aggregation

“…S4). The fact that flunarizine was identified in an assay based on S. cerevisiae yeast cells that lack known homologues of histamine receptors [48] is an additional argument indicating that the H1 receptor is not involved in the anti-prion effect of the drug tested. Finally, since 5 out of the 13 inactive compounds tested also bind to H1 receptor, we concluded that H1 receptor is unlikely to be involved in PrP Sc clearance.…”

l-Thyroxine induces thermotolerance in yeast

“…The CSR to adverse environmental/ microenvironmental conditions is governed by evolutionary conserved endogenous multicomponent processes, including heat shock protein (Hsp) expression and ion homeostasis (Święciło 2016). Physical, chemical, or physiological stimuli, such as heat, drugs, and hormones trigger and/or modulate CSR (Delitheos et al 2010;Papamichael et al 2006;Papamichael et al 2013). The evolutionary conservation of the basic physiological and biochemical, cellular, and molecular mechanisms between yeasts and higher eukaryotes made the yeast an established experimental model for the pharmacological inves-tigation of the CSR and the adaptive and protective mechanisms underlying drug resistance (Verghese et al 2012).…”

Μοριακοί Και Κυτταρικοί Ανοσολογικοί Μηχανισμοί Κατά Τις Αντιδράσεις Υπερευαισθησίας Στα Μη Στερεοειδή Αντιφλεγμονώδη Φάρμακα

“…Η ισταμίνη ασκεί τις δράσεις της μέσω σύνδεσης με τους υποδοχείς Η 1 -Η 4 (Εικόνα 1.17) (Bongers et al, 2010• Panula et al, 2015, αν και έχουν παρατηρηθεί δράσεις της ισταμίνης ανεξάρτητες των υποδοχέων σε διάφορα συστήματα και οργανισμούς (Walther et al, 2011• Kyriakidis et al, 2012• Kyriakidis and Tiligada, 2013• Papamichael et al, 2013.…”