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

Kleimaier, D.; Goerke, S.; Nies, C. 1; Zaiss, M.; Kunz, P.; Bachert, P.; Ladd, M. E.; Gottwald, E. ORCID iD icon 1; Schad, L. R.
1 Institut für Funktionelle Grenzflächen (IFG), Karlsruher Institut für Technologie (KIT)

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.

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 Scopus
Dimensions
Web of Science
Globale Ziele für nachhaltige Entwicklung Ziel 3 – Gesundheit und Wohlergehen

Verlagsausgabe §
DOI: 10.5445/IR/1000122757
Veröffentlicht am 30.08.2020
Originalveröffentlichung
DOI: 10.1038/s41598-020-68022-1
Scopus
Zitationen: 12
Web of Science
Zitationen: 11
Dimensions
Zitationen: 12
Seitenaufrufe: 124
seit 31.08.2020
Downloads: 88
seit 31.08.2020
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