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 ME, Gottwald E, Schad LR (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Scientific Reports Nature Publishing Group: Open Access Journals - Option B

Book Volume: 10

Article Number: 11118

Journal Issue: 1

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.

Authors with CRIS profile

Moritz Zaiß Professur für Multimodale Bildgebung in der klinischen Forschung

Involved external institutions

Ruprecht-Karls-Universität Heidelberg DE Germany (DE) Deutsches Krebsforschungszentrum (DKFZ) DE Germany (DE) Karlsruhe Institute of Technology (KIT) DE Germany (DE)

How to cite

APA:

Kleimaier, D., Goerke, S., Nies, C., Zaiß, M., Kunz, P., Bachert, P.,... Schad, L.R. (2020). The cellular heat shock response monitored by chemical exchange saturation transfer MRI. Scientific Reports, 10(1). https://doi.org/10.1038/s41598-020-68022-1

MLA:

Kleimaier, Dennis, et al. "The cellular heat shock response monitored by chemical exchange saturation transfer MRI." Scientific Reports 10.1 (2020).

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