The cellular heat shock response monitored by chemical exchange saturation transfer MRI

• Verfasst von: Kleimaier, Dennis [VerfasserIn]
• Verfasst von: Görke, Steffen [VerfasserIn]
• Verfasst von: Nies, Cordula [VerfasserIn]
• Verfasst von: Zaiss, Moritz [VerfasserIn]
• Verfasst von: Kunz, Patrick [VerfasserIn]
• Verfasst von: Bachert, Peter [VerfasserIn]
• Verfasst von: Ladd, Mark E. [VerfasserIn]
• Verfasst von: Gottwald, Eric [VerfasserIn]
• Verfasst von: Schad, Lothar R. [VerfasserIn]
• Titel: The cellular heat shock response monitored by chemical exchange saturation transfer MRI
• Verf.angabe: Dennis Kleimaier, Steffen Goerke, Cordula Nies, Moritz Zaiss, Patrick Kunz, Peter Bachert, Mark E. Ladd, Eric Gottwald & Lothar R. Schad
• E-Jahr: 2020
• Jahr: 06 June 2020
• Fussnoten: Gesehen am 02.09.2020
• Titel Quelle: Enthalten in: Scientific reports
• Ort Quelle: [London] : Macmillan Publishers Limited, part of Springer Nature, 2011
• Jahr Quelle: 2020
• Band/Heft Quelle: 10(2020) Artikel-Nummer 11118, 12 Seiten
• ISSN Quelle: 2045-2322
• DOI: doi:10.1038/s41598-020-68022-1
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1728634512

Abstract

CEST-MRI of the rNOE signal has been demonstrated in vitro to be closely linked to the protein conformational state. As the detectability of denaturation and aggregation processes on a physiologically relevant scale in living organisms has yet to be verified, the aim of this study was to perform heat-shock experiments with living cells to monitor the cellular heat-shock response of the rNOE CEST signal. Cancer cells (HepG2) were dynamically investigated after a mild, non-lethal heat-shock of 42 °C for 20 min using an MR-compatible bioreactor system at 9.4 T. Reliable and fast high-resolution CEST imaging was realized by a relaxation-compensated 2-point contrast metric. After the heat-shock, a substantial decrease of the rNOE CEST signal by 8.0 ± 0.4% followed by a steady signal recovery within a time of 99.1 ± 1.3 min was observed in two independent trials. This continuous signal recovery is in coherence with chaperone-induced refolding of heat-shock induced protein aggregates. We demonstrated that protein denaturation processes influence the CEST-MRI signal on a physiologically relevant scale. Thus, the protein folding state is, along with concentration changes, a relevant physiological parameter for the interpretation of CEST signal changes in diseases that are associated with pathological changes in protein expression, like cancer and neurodegenerative diseases.