The cellular heat shock response monitored by chemical exchange saturation transfer MRI
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 hea...
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| Main Authors: | , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
06 June 2020
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| In: |
Scientific reports
Year: 2020, Volume: 10 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-68022-1 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41598-020-68022-1 Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41598-020-68022-1 
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| Author Notes: | Dennis Kleimaier, Steffen Goerke, Cordula Nies, Moritz Zaiss, Patrick Kunz, Peter Bachert, Mark E. Ladd, Eric Gottwald & Lothar R. Schad |
| Summary: | 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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| Item Description: | Gesehen am 02.09.2020 |
| Physical Description: | Online Resource |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-68022-1 |