Inhibition of cardiac PERK signaling promotes peripartum cardiac dysfunction

Abstract Peripartum cardiomyopathy (PPCM) is a life-threatening heart failure occurring in the peripartum period. Although mal-angiogenesis, induced by the 16-kDa N-terminal prolactin fragment (16 K PRL), is involved in the pathogenesis, the effect of full-length prolactin (23 K PRL) is poorly under...

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Autores principales:	Takashi Shimizu, Akashi Taguchi, Yoshiki Higashijima, Yasuharu Kanki, Ryo Nakaki, Yoshihiro Urade, Youichiro Wada
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bd475300e3704da38011878cdf321845
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spelling	oai:doaj.org-article:bd475300e3704da38011878cdf3218452021-12-02T15:14:55ZInhibition of cardiac PERK signaling promotes peripartum cardiac dysfunction10.1038/s41598-021-98344-72045-2322https://doaj.org/article/bd475300e3704da38011878cdf3218452021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98344-7https://doaj.org/toc/2045-2322Abstract Peripartum cardiomyopathy (PPCM) is a life-threatening heart failure occurring in the peripartum period. Although mal-angiogenesis, induced by the 16-kDa N-terminal prolactin fragment (16 K PRL), is involved in the pathogenesis, the effect of full-length prolactin (23 K PRL) is poorly understood. We transfected neonate rat cardiomyocytes with plasmids containing 23 K PRL or 16 K PRL in vitro and found that 23 K PRL, but not 16 K PRL, upregulated protein kinase RNA-like endoplasmic reticulum kinase (PERK) signaling, and hypoxia promoted this effect. During the perinatal period, cardiomyocyte-specific PERK homogenous knockout (CM-KO) mice showed PPCM phenotypes after consecutive deliveries. Downregulation of PERK or JAK/STAT signaling and upregulation of apoptosis were observed in CM-KO mouse hearts. Moreover, in bromocriptine-treated CM-KO mice, cardiac function did not improve and cardiomyocyte apoptosis was not suppressed during the peripartum period. These results demonstrate that interaction between 23 K PRL and PERK signaling is cardioprotective during the peripartum term.Takashi ShimizuAkashi TaguchiYoshiki HigashijimaYasuharu KankiRyo NakakiYoshihiro UradeYouichiro WadaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takashi Shimizu Akashi Taguchi Yoshiki Higashijima Yasuharu Kanki Ryo Nakaki Yoshihiro Urade Youichiro Wada Inhibition of cardiac PERK signaling promotes peripartum cardiac dysfunction
description	Abstract Peripartum cardiomyopathy (PPCM) is a life-threatening heart failure occurring in the peripartum period. Although mal-angiogenesis, induced by the 16-kDa N-terminal prolactin fragment (16 K PRL), is involved in the pathogenesis, the effect of full-length prolactin (23 K PRL) is poorly understood. We transfected neonate rat cardiomyocytes with plasmids containing 23 K PRL or 16 K PRL in vitro and found that 23 K PRL, but not 16 K PRL, upregulated protein kinase RNA-like endoplasmic reticulum kinase (PERK) signaling, and hypoxia promoted this effect. During the perinatal period, cardiomyocyte-specific PERK homogenous knockout (CM-KO) mice showed PPCM phenotypes after consecutive deliveries. Downregulation of PERK or JAK/STAT signaling and upregulation of apoptosis were observed in CM-KO mouse hearts. Moreover, in bromocriptine-treated CM-KO mice, cardiac function did not improve and cardiomyocyte apoptosis was not suppressed during the peripartum period. These results demonstrate that interaction between 23 K PRL and PERK signaling is cardioprotective during the peripartum term.
format	article
author	Takashi Shimizu Akashi Taguchi Yoshiki Higashijima Yasuharu Kanki Ryo Nakaki Yoshihiro Urade Youichiro Wada
author_facet	Takashi Shimizu Akashi Taguchi Yoshiki Higashijima Yasuharu Kanki Ryo Nakaki Yoshihiro Urade Youichiro Wada
author_sort	Takashi Shimizu
title	Inhibition of cardiac PERK signaling promotes peripartum cardiac dysfunction
title_short	Inhibition of cardiac PERK signaling promotes peripartum cardiac dysfunction
title_full	Inhibition of cardiac PERK signaling promotes peripartum cardiac dysfunction
title_fullStr	Inhibition of cardiac PERK signaling promotes peripartum cardiac dysfunction
title_full_unstemmed	Inhibition of cardiac PERK signaling promotes peripartum cardiac dysfunction
title_sort	inhibition of cardiac perk signaling promotes peripartum cardiac dysfunction
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/bd475300e3704da38011878cdf321845
work_keys_str_mv	AT takashishimizu inhibitionofcardiacperksignalingpromotesperipartumcardiacdysfunction AT akashitaguchi inhibitionofcardiacperksignalingpromotesperipartumcardiacdysfunction AT yoshikihigashijima inhibitionofcardiacperksignalingpromotesperipartumcardiacdysfunction AT yasuharukanki inhibitionofcardiacperksignalingpromotesperipartumcardiacdysfunction AT ryonakaki inhibitionofcardiacperksignalingpromotesperipartumcardiacdysfunction AT yoshihirourade inhibitionofcardiacperksignalingpromotesperipartumcardiacdysfunction AT youichirowada inhibitionofcardiacperksignalingpromotesperipartumcardiacdysfunction
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Inhibition of cardiac PERK signaling promotes peripartum cardiac dysfunction

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