Down-regulation of PDK4 is Critical for the Switch of Carbohydrate Catabolism during Syncytialization of Human Placental Trophoblasts

Abstract Pyruvate dehydrogenase kinase (PDK) is known as a gatekeeper directing the carbon flux into glycolysis via inhibition of the pyruvate dehydrogenase complex. During syncytialization of placental trophoblasts, both ATP production and oxygen consumption are increased to meet enhanced energetic...

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Autores principales:	Xiaohui Liu, Rujuan Zuo, Yirong Bao, Xiaoxian Qu, Kang Sun, Hao Ying
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/20adde03dac6496d951312af85412699
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spelling	oai:doaj.org-article:20adde03dac6496d951312af854126992021-12-02T12:31:49ZDown-regulation of PDK4 is Critical for the Switch of Carbohydrate Catabolism during Syncytialization of Human Placental Trophoblasts10.1038/s41598-017-09163-82045-2322https://doaj.org/article/20adde03dac6496d951312af854126992017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09163-8https://doaj.org/toc/2045-2322Abstract Pyruvate dehydrogenase kinase (PDK) is known as a gatekeeper directing the carbon flux into glycolysis via inhibition of the pyruvate dehydrogenase complex. During syncytialization of placental trophoblasts, both ATP production and oxygen consumption are increased to meet enhanced energetic demands by syntiotrophoblasts. We hypothesized that down-regulation of PDK expression may play a central role in the switch from glycolysis to oxidative phosphorylation (OXPHOS) during syncytialization. By using primary human trophoblasts, we demonstrated that PDK4 was the dominating PDK isoform in human cytotrophoblasts, and its abundance was substantially decreased upon syncytialization, which was accompanied by decreases in lactate production and increases in ATP production. Knock-down of PDK4 expression reduced lactate production and increased ATP production, while over-expression of PDK4 increased lactate production and decreased ATP production, indicating that down-regulation of PDK4 is key to the shift from glycolysis to OXPHOS during syncytialization. Moreover, human chorionic gonadotropin (hCG)/cAMP/PKA pathway was demonstrated to be involved in the down-regulation of PDK4 expression upon syncytialization. Taken together, our findings disclosed that down-regulation of PDK4 is critical for the metabolic shift from glycolysis to OXPHOS during syncytialization, which may be a prerequisite for the proper implementation of syncytiotrophoblast functions.Xiaohui LiuRujuan ZuoYirong BaoXiaoxian QuKang SunHao YingNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaohui Liu Rujuan Zuo Yirong Bao Xiaoxian Qu Kang Sun Hao Ying Down-regulation of PDK4 is Critical for the Switch of Carbohydrate Catabolism during Syncytialization of Human Placental Trophoblasts
description	Abstract Pyruvate dehydrogenase kinase (PDK) is known as a gatekeeper directing the carbon flux into glycolysis via inhibition of the pyruvate dehydrogenase complex. During syncytialization of placental trophoblasts, both ATP production and oxygen consumption are increased to meet enhanced energetic demands by syntiotrophoblasts. We hypothesized that down-regulation of PDK expression may play a central role in the switch from glycolysis to oxidative phosphorylation (OXPHOS) during syncytialization. By using primary human trophoblasts, we demonstrated that PDK4 was the dominating PDK isoform in human cytotrophoblasts, and its abundance was substantially decreased upon syncytialization, which was accompanied by decreases in lactate production and increases in ATP production. Knock-down of PDK4 expression reduced lactate production and increased ATP production, while over-expression of PDK4 increased lactate production and decreased ATP production, indicating that down-regulation of PDK4 is key to the shift from glycolysis to OXPHOS during syncytialization. Moreover, human chorionic gonadotropin (hCG)/cAMP/PKA pathway was demonstrated to be involved in the down-regulation of PDK4 expression upon syncytialization. Taken together, our findings disclosed that down-regulation of PDK4 is critical for the metabolic shift from glycolysis to OXPHOS during syncytialization, which may be a prerequisite for the proper implementation of syncytiotrophoblast functions.
format	article
author	Xiaohui Liu Rujuan Zuo Yirong Bao Xiaoxian Qu Kang Sun Hao Ying
author_facet	Xiaohui Liu Rujuan Zuo Yirong Bao Xiaoxian Qu Kang Sun Hao Ying
author_sort	Xiaohui Liu
title	Down-regulation of PDK4 is Critical for the Switch of Carbohydrate Catabolism during Syncytialization of Human Placental Trophoblasts
title_short	Down-regulation of PDK4 is Critical for the Switch of Carbohydrate Catabolism during Syncytialization of Human Placental Trophoblasts
title_full	Down-regulation of PDK4 is Critical for the Switch of Carbohydrate Catabolism during Syncytialization of Human Placental Trophoblasts
title_fullStr	Down-regulation of PDK4 is Critical for the Switch of Carbohydrate Catabolism during Syncytialization of Human Placental Trophoblasts
title_full_unstemmed	Down-regulation of PDK4 is Critical for the Switch of Carbohydrate Catabolism during Syncytialization of Human Placental Trophoblasts
title_sort	down-regulation of pdk4 is critical for the switch of carbohydrate catabolism during syncytialization of human placental trophoblasts
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/20adde03dac6496d951312af85412699
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Down-regulation of PDK4 is Critical for the Switch of Carbohydrate Catabolism during Syncytialization of Human Placental Trophoblasts

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