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

Kleimaier, D.; Goerke, S.; Nies, C.; Zaiss, M.; Kunz, P.; Bachert, P.; Ladd, M. E.; Gottwald, E.; Schad, L. R.

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.

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Verlagsausgabe §
DOI: 10.5445/IR/1000122757
Veröffentlicht am 30.08.2020
Originalveröffentlichung
DOI: 10.1038/s41598-020-68022-1
Scopus
Zitationen: 3
Web of Science
Zitationen: 4
Dimensions
Zitationen: 5
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Funktionelle Grenzflächen (IFG)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2020
Sprache Englisch
Identifikator ISSN: 2045-2322
KITopen-ID: 1000122757
HGF-Programm 47.02.06 (POF III, LK 01) Zellpopul.auf Biofunk.Oberflächen IFG
Erschienen in Scientific reports
Verlag Nature Research
Band 10
Heft 1
Seiten Art. Nr.: 11118
Vorab online veröffentlicht am 06.07.2020
Nachgewiesen in Web of Science
Dimensions
Scopus
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