Lactic Acid Transport Mediated by Aquaporin-9: Implications on the Pathophysiology of Preeclampsia

Aquaporin-9 (AQP9) expression is significantly increased in preeclamptic placentas. Since feto-maternal water transfer is not altered in preeclampsia, the main role of AQP9 in human placenta is unclear. Given that AQP9 is also a metabolite channel, we aimed to evaluate the participation of AQP9 in l...

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Autores principales:	Yollyseth Medina, Lucas Acosta, Julieta Reppetti, Ana Corominas, Juanita Bustamante, Natalia Szpilbarg, Alicia E. Damiano
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	AQP9 lactic acid transport mitochondria human placenta preeclampsia Physiology QP1-981
Acceso en línea:	https://doaj.org/article/867301af19cf439f897dfd4581317155
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spelling	oai:doaj.org-article:867301af19cf439f897dfd45813171552021-12-02T11:45:24ZLactic Acid Transport Mediated by Aquaporin-9: Implications on the Pathophysiology of Preeclampsia1664-042X10.3389/fphys.2021.774095https://doaj.org/article/867301af19cf439f897dfd45813171552021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphys.2021.774095/fullhttps://doaj.org/toc/1664-042XAquaporin-9 (AQP9) expression is significantly increased in preeclamptic placentas. Since feto-maternal water transfer is not altered in preeclampsia, the main role of AQP9 in human placenta is unclear. Given that AQP9 is also a metabolite channel, we aimed to evaluate the participation of AQP9 in lactate transfer across the human placenta. Explants from normal term placentas were cultured in low glucose medium with or without L-lactic acid and in the presence and absence of AQP9 blockers (0.3 mM HgCl2 or 0.5 mM Phloretin). Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and lactate dehydrogenase release. Apoptotic indexes were analyzed by Bax/Bcl-2 ratio and Terminal Deoxynucleotidyltransferase-Mediated dUTP Nick-End Labeling assay. Heavy/large and light/small mitochondrial subpopulations were obtained by differential centrifugation, and AQP9 expression was detected by Western blot. We found that apoptosis was induced when placental explants were cultured in low glucose medium while the addition of L-lactic acid prevented cell death. In this condition, AQP9 blocking increased the apoptotic indexes. We also confirmed the presence of two mitochondrial subpopulations which exhibit different morphologic and metabolic states. Western blot revealed AQP9 expression only in the heavy/large mitochondrial subpopulation. This is the first report that shows that AQP9 is expressed in the heavy/large mitochondrial subpopulation of trophoblasts. Thus, AQP9 may mediate not only the lactic acid entrance into the cytosol but also into the mitochondria. Consequently, its lack of functionality in preeclamptic placentas may impair lactic acid utilization by the placenta, adversely affecting the survival of the trophoblast cells and enhancing the systemic endothelial dysfunction.Yollyseth MedinaLucas AcostaJulieta ReppettiAna CorominasJuanita BustamanteNatalia SzpilbargAlicia E. DamianoAlicia E. DamianoFrontiers Media S.A.articleAQP9lactic acid transportmitochondriahuman placentapreeclampsiaPhysiologyQP1-981ENFrontiers in Physiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	AQP9 lactic acid transport mitochondria human placenta preeclampsia Physiology QP1-981
spellingShingle	AQP9 lactic acid transport mitochondria human placenta preeclampsia Physiology QP1-981 Yollyseth Medina Lucas Acosta Julieta Reppetti Ana Corominas Juanita Bustamante Natalia Szpilbarg Alicia E. Damiano Alicia E. Damiano Lactic Acid Transport Mediated by Aquaporin-9: Implications on the Pathophysiology of Preeclampsia
description	Aquaporin-9 (AQP9) expression is significantly increased in preeclamptic placentas. Since feto-maternal water transfer is not altered in preeclampsia, the main role of AQP9 in human placenta is unclear. Given that AQP9 is also a metabolite channel, we aimed to evaluate the participation of AQP9 in lactate transfer across the human placenta. Explants from normal term placentas were cultured in low glucose medium with or without L-lactic acid and in the presence and absence of AQP9 blockers (0.3 mM HgCl2 or 0.5 mM Phloretin). Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and lactate dehydrogenase release. Apoptotic indexes were analyzed by Bax/Bcl-2 ratio and Terminal Deoxynucleotidyltransferase-Mediated dUTP Nick-End Labeling assay. Heavy/large and light/small mitochondrial subpopulations were obtained by differential centrifugation, and AQP9 expression was detected by Western blot. We found that apoptosis was induced when placental explants were cultured in low glucose medium while the addition of L-lactic acid prevented cell death. In this condition, AQP9 blocking increased the apoptotic indexes. We also confirmed the presence of two mitochondrial subpopulations which exhibit different morphologic and metabolic states. Western blot revealed AQP9 expression only in the heavy/large mitochondrial subpopulation. This is the first report that shows that AQP9 is expressed in the heavy/large mitochondrial subpopulation of trophoblasts. Thus, AQP9 may mediate not only the lactic acid entrance into the cytosol but also into the mitochondria. Consequently, its lack of functionality in preeclamptic placentas may impair lactic acid utilization by the placenta, adversely affecting the survival of the trophoblast cells and enhancing the systemic endothelial dysfunction.
format	article
author	Yollyseth Medina Lucas Acosta Julieta Reppetti Ana Corominas Juanita Bustamante Natalia Szpilbarg Alicia E. Damiano Alicia E. Damiano
author_facet	Yollyseth Medina Lucas Acosta Julieta Reppetti Ana Corominas Juanita Bustamante Natalia Szpilbarg Alicia E. Damiano Alicia E. Damiano
author_sort	Yollyseth Medina
title	Lactic Acid Transport Mediated by Aquaporin-9: Implications on the Pathophysiology of Preeclampsia
title_short	Lactic Acid Transport Mediated by Aquaporin-9: Implications on the Pathophysiology of Preeclampsia
title_full	Lactic Acid Transport Mediated by Aquaporin-9: Implications on the Pathophysiology of Preeclampsia
title_fullStr	Lactic Acid Transport Mediated by Aquaporin-9: Implications on the Pathophysiology of Preeclampsia
title_full_unstemmed	Lactic Acid Transport Mediated by Aquaporin-9: Implications on the Pathophysiology of Preeclampsia
title_sort	lactic acid transport mediated by aquaporin-9: implications on the pathophysiology of preeclampsia
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/867301af19cf439f897dfd4581317155
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Lactic Acid Transport Mediated by Aquaporin-9: Implications on the Pathophysiology of Preeclampsia

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