TY - JOUR
T1 - Torpor-arousal cycles in Syrian hamster heart are associated with transient activation of the protein quality control system
AU - Wiersma, Marit
AU - Beuren, Thais M.A.
AU - de Vrij, Edwin L.
AU - Reitsema, Vera A.
AU - Bruintjes, Jantje J.
AU - Bouma, Hjalmar R.
AU - Brundel, Bianca J.J.M.
AU - Henning, Robert H.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - 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.
AB - 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.
KW - Autophagy
KW - ER stress
KW - Heart
KW - Hibernation
KW - Mesocricetus auratus
KW - Protein quality control
KW - Unfolded protein response
UR - http://www.scopus.com/inward/record.url?scp=85048403970&partnerID=8YFLogxK
U2 - 10.1016/j.cbpb.2018.06.001
DO - 10.1016/j.cbpb.2018.06.001
M3 - Article
C2 - 29894736
AN - SCOPUS:85048403970
VL - 223
SP - 23
EP - 28
JO - Comparative biochemistry and physiology b-biochemistry & molecular biology
JF - Comparative biochemistry and physiology b-biochemistry & molecular biology
SN - 1096-4959
ER -