Journal Article

DKFZ-2020-01222

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The cellular heat shock response monitored by chemical exchange saturation transfer MRI.

Kleimaier, D. ; Goerke, S. (First author)DKFZ* ; Nies, C. ; Zaiss, M. ; Kunz, P.DKFZ* ; Bachert, P.DKFZ* ; Ladd, M. E.DKFZ* ; Gottwald, E. ; Schad, L. R.

2020
Macmillan Publishers Limited, part of Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41598-020-68022-1

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.

Note: #EA:E020#

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Contributing Institute(s):

1. E020 Med. Physik in der Radiologie (E020)

Research Program(s):

1. 315 - Imaging and radiooncology (POF3-315) (POF3-315)

Appears in the scientific report 2020

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