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.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Kleimaier D,Goerke S,Nies C,Zaiss M,Kunz P,Bachert P,Ladd ME,Gottwald E,Schad LRdoi
10.1038/s41598-020-68022-1subject
Has Abstractpub_date
2020-07-06 00:00:00pages
11118issue
1issn
2045-2322pii
10.1038/s41598-020-68022-1journal_volume
10pub_type
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