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Comp Biochem Physiol B Biochem Mol Biol. 2018 Jun 9;223:23-28. doi: 10.1016/j.cbpb.2018.06.001. [Epub ahead of print]

Torpor-arousal cycles in Syrian hamster heart are associated with transient activation of the protein quality control system.

Author information

1
Department of Physiology, Amsterdam Cardiovascular Sciences, VU University Medical Center, Amsterdam, The Netherlands; Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, The Netherlands. Electronic address: m.wiersma1@vumc.nl.
2
Department of Physiology, Amsterdam Cardiovascular Sciences, VU University Medical Center, Amsterdam, The Netherlands; Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, The Netherlands.
3
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, The Netherlands; Department of Surgery, Martini Hospital, Groningen, The Netherlands.
4
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, The Netherlands.
5
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, The Netherlands; Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Abstract

Hibernation consists of torpor, with marked suppression of metabolism and physiological functions, alternated with arousal periods featuring their full restoration. The heart is particularly challenged, exemplified by its rate reduction from 400 to 5-10 beats per minute during torpor in Syrian hamsters. In addition, during arousals, the heart needs to accommodate the very rapid return to normal function, which lead to our hypothesis that cardiac function during hibernation is supported by maintenance of protein homeostasis through adaptations in the protein quality control (PQC) system. Hereto, we examined autophagy, the endoplasmic reticulum (ER) unfolded protein (UPRER) response and the heat shock response (HSR) in Syrian hamster hearts during torpor and arousal. Transition from torpor to arousal (1.5 h) was associated with stimulation of the PQC system during early arousal, demonstrated by induction of autophagosomes, as shown by an increase in LC3B-II protein abundance, likely related to the activation of the UPRER during late torpor in response to proteotoxic stress. The HSR was not activated during torpor or arousal. Our results demonstrate activation of the cardiac PQC system - particularly autophagosomal degradation - in early arousal in response to cardiac stress, to clear excess aberrant or damaged proteins, being gradually formed during the torpor bout and/or the rapid increase in heart rate during the transition from torpor to arousal. This mechanism may enable the large gain in cardiac function during the transition from torpor to arousal, which may hold promise to further understand 'hibernation' of cardiomyocytes in human heart disease.

KEYWORDS:

Autophagy; ER stress; Heart; Hibernation; Mesocricetus auratus; Protein quality control; Unfolded protein response

PMID:
29894736
DOI:
10.1016/j.cbpb.2018.06.001

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