Placental programmed cell death: insights into the role of aquaporins

Szpilbarg, Natalia; Castro-Parodi, Mauricio; Reppetti, Julieta; Repetto, Marisa G.; Maskin, Bernardo; Martínez, Nora; Damiano, Alicia E.

doi:10.1093/molehr/gav063

Cited by 26 publications

(17 citation statements)

References 30 publications

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“…Located across the cell membrane, AQP3, besides transporting water, glycerol, etc., can also synthesize TG via glycerol kinase catalysis [21]. A previous study showed that inhibiting the expression of AQP3 protein mitigated apoptosis reactions of placenta [7]. Alejandra et al [22] found that silencing of placental AQP3 protein induced early-onset preeclampsia, which was probably attributed to the impaired migration of extravillous trophoblast cells and the failure in the remodeling of maternal spiral arteries afterward.…”

Section: Discussionmentioning

confidence: 99%

“…The fluctuation of AQP3 protein has been reported to be closely related to physiological and pathological reactions, such as reproduction, breast secretion, gestational diabetes mellitus, gynecological tumors, hypertensions, and so on [5, 6]. Furthermore, an in vitro study has shown that AQP3 participated in the oxidative stress response and the apoptosis of placenta nourishing cells [7]. Therefore, we speculate that the imbalance of placental AQP3 might be a key cause of preeclampsia as well as a variety of clinical manifestations.…”

Section: Introductionmentioning

confidence: 99%

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Altered Expressions of AQP3 and ADP Are Closely Related with the Risk of Preeclampsia Occurrence

Zhou

Zhang

Bai

et al. 2020

Gynecol Obstet Invest

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To investigate the expression of aquaporin 3 (AQP3) in placenta and fetal membranes and the level of adiponectin (ADP) in the umbilical cord blood of severe preeclampsia and to analyze the relationship between the 2 proteins and severe preeclampsia, 60 pregnant women with severe preeclampsia were recruited as the case group and another group of 60 normal pregnant women in the same gestation period were selected as the control. After parturition, the transcriptional levels of AQP3 mRNA in placenta and fetal membranes were evaluated with RT-PCR. The expressions of AQP3 protein in the placenta and fetal membranes were determined by immunohistochemistry and Western blot. Meanwhile, the expression of ADP in umbilical artery blood was detected by ELISA. The content of triglyceride (TG), lowdensity lipoprotein cholesterol (LDL-C), and LDL-C/highdensity lipoprotein cholesterol in the case group was significantly higher than that in the control group. Multivariate logistic regression analysis showed that the level of TG was related to the onset of severe preeclampsia (OR 2.589). The relative expression of AQP3 mRNA and expression of AQP3 protein in placenta tissue of the case group were significantly lower than those of the control group, whereas in fetal membranes, they were significantly higher. The results of ELISA showed that the level of ADP in umbilical cord blood of neonates in the case group increased remarkably compared with that of the control group.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Altered Expressions of AQP3 and ADP Are Closely Related with the Risk of Preeclampsia Occurrence

Zhou

Zhang

Bai

et al. 2020

Gynecol Obstet Invest

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“…We previously demonstrated that upregulation of AQP3 expression contributes to the proliferative activity of GC cells 3. AQP3 expression has also been implicated in the regulation of cell apoptosis 35,36. But the association between AQP3 expression and cell apoptosis in GC has not been elucidated in detail.…”

Section: Discussionmentioning

confidence: 99%

Silencing of AQP3 induces apoptosis of gastric cancer cells via downregulation of glycerol intake and downstream inhibition of lipogenesis and autophagy

Liang

Zhang

et al. 2017

OTT

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Gastric cancer (GC) has a poor prognosis and is a leading cause of cancer-related death. Optimal therapeutic targets have not been identified. AQP3 is capable of transporting glycerol across the cytomembrane. Previous studies have shown that AQP3 is involved in proliferation, invasion and migration by regulating glycerol and lipid metabolism in diverse cancer cell types. However, the potential roles of glycerol and lipid metabolism in AQP3-related cell apoptosis in GC remain unclear. In this study, we observed that AQP3 expression was upregulated in tumor tissues, and positively correlated with tumor size, lymph node metastasis and glycerol concentration in human GC samples. Silencing of AQP3 resulted in decreased glycerol intake and impaired lipid synthesis, which contributed to increased cell apoptosis. Furthermore, inhibition of autophagy induced by AQP3 knockdown promoted cell apoptosis. Administration of either glycerol or rapamycin restored cell viability, and overexpression of AQP3 increased cell viability by upregulating cellular glycerol metabolism and autophagy. Our study demonstrates that the increase in cell apoptosis of AQP3-deficient GC cells is a consequence of reduced glycerol uptake and lipogenesis and is associated with autophagy inhibition induced by AQP3 deficiency.

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“…Another study proved that AQP3 has a critical role in the regulation of placental apoptosis in pathological placentas (e.g., in preeclampsia). The loss of water via AQP3 from the cells during the apoptotic volume decrease is important to the progression of apoptosis [ 42 ].…”

Section: Maternal–fetal Fluid Flowmentioning

confidence: 99%

Aquaporins during Pregnancy: Their Function and Significance

Ducza

Csányi

Gáspár

2017

IJMS

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Water is the major component of cells and tissues, and the movement of water across the cell membrane is a fundamental property of life. Until the discovery of the first water channel, aquaporin, it was long assumed that the transport of water was due to simple diffusion through the lipid bilayer membrane that encloses cells. Aquaporin (AQP) molecules were first discovered in the human uterus in 1994, and since then several studies have investigated these channels in the female reproductive system. The expressions of AQPs have been proven in the reproductive system. Their levels are altered during the implantation process, both in the uterus and the fetal cells, and participate in the control of the flow of amniotic fluid. They seem to be very important for the normal placental functions. AQPs are present during parturition, participating in the control of pregnant myometrial contractions and cervical ripening. However, most of the physiological and regulatory roles of AQPs are not clarified in the reproductive tract. Furthermore, no satisfactory knowledge is available about their sensitivities to different drugs. AQP-selective ligands may contribute to the development of new drug candidates and the therapy of several reproductive disorders.

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Placental programmed cell death: insights into the role of aquaporins

Abstract: This study was supported by UBACyT 20020090200025 and 20020110200207 grants and PIP-CONICET 11220110100561 grant, and the authors have no conflict of interest to declare.

Cited by 26 publications

References 30 publications

Altered Expressions of AQP3 and ADP Are Closely Related with the Risk of Preeclampsia Occurrence

Altered Expressions of AQP3 and ADP Are Closely Related with the Risk of Preeclampsia Occurrence

Silencing of AQP3 induces apoptosis of gastric cancer cells via downregulation of glycerol intake and downstream inhibition of lipogenesis and autophagy

Aquaporins during Pregnancy: Their Function and Significance

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