Increased expression and phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoforms in urinary exosomes in pre-eclampsia

Ellis, Rebecca; Katerelos, Marina; Choy, Suet-Wan; Cook, Natasha; Lee, M.; Paizis, Kathy; Pell, Gaby S.; Walker, Susan; Power, David A.; Mount, Peter F.

doi:10.1186/s12967-019-1806-6

Cited by 22 publications

(8 citation statements)

References 38 publications

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“…It has been reported that the phosphorylation of PFKFB2 is critical for its activation. 16) Consistently, compared with the control groups, the MIpost mice demonstrated remarkably elevated phosphorylation levels of PFKFB2 in cardiac tissues ( Figure 1B). The IHC staining further revealed that the protein expression of PFKFB2 was increased in the peri-infarct region of heart tissues from the MI mice ( Figure 1C), suggesting that PFKFB2 may be closely correlated with the development of MI.…”

Section: Resultssupporting

confidence: 60%

HIF-1/AKT Signaling-Activated PFKFB2 Alleviates Cardiac Dysfunction and Cardiomyocyte Apoptosis in Response to Hypoxia

Feng

Liu

et al. 2021

Int. Heart J.

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Myocardial infarction (MI) is the most prevalent disease with severe mortality, and hypoxia-induced cardiac injury and cardiomyocyte apoptosis are the significant and harmful consequences of this disease. The cross talk between hypoxia signaling and glycolysis energy flux plays a critical role in modulating MI-related heart disorder. However, the underlying mechanism remains unclear. Here, we aimed to explore the effect of a key glycolytic enzyme of 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 2 (PFKFB2) on cardiac dysfunction and apoptosis in response to hypoxia. Our data demonstrated that the mRNA and protein expression of PFKFB 2 were significantly elevated in the MI mice. The MI treatment promoted the activation of PFKFB2 in vivo, as presented by the remarkably increased phosphorylation levels of PFKFB2. PFKFB2 depletion enhanced MIinduced cardiac dysfunction and cardiomyocyte apoptosis in the MI mouse model. Moreover, hypoxia treatment dramatically upregulated the expression and activation of PFKFB2 in a time-dependent manner in cardiomyocytes. Hypoxia-stimulated PFKFB2 relieved hypoxia-induced cardiomyocyte apoptosis in vitro. PFKFB2 activated the fructose-2, 6-bisphosphate (Fru-2, 6-p2)/PFK/anaerobic adenosine triphosphate (ATP) glycolysis energy flux in response to hypoxia in cardiomyocytes. Mechanically, hypoxia-activated PFKFB2 by stimulating the hypoxia-inducible factor 1 (HIF-1)/ATK signaling. Thus, we conclude that HIF-1/AKT axis-activated PFKFB2 alleviates cardiac dysfunction and cardiomyocyte apoptosis in response to hypoxia. Our finding presents a new insight into the mechanism by which HIF-1/AKT/PFKFB2 signaling modulates MI-related heart disorder under the hypoxia condition, providing potential therapeutic targets and strategy for hypoxia-related myocardial injury.

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Section: Resultssupporting

confidence: 60%

HIF-1/AKT Signaling-Activated PFKFB2 Alleviates Cardiac Dysfunction and Cardiomyocyte Apoptosis in Response to Hypoxia

Feng

Liu

et al. 2021

Int. Heart J.

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“…PFKFB3 facilitates the allosteric activation of PFK‐1 through the production of F‐2,6‐BP, thereby accelerating glycolytic flux. A prior study confirmed that PFKFB3 protein expression and phosphorylation were relatively elevated in urinary exosomes isolated from preeclamptic patients 164 . Subsequently, researchers investigated the mechanism of PFKFB3 in preeclampsia.…”

Section: Glycolysis In Pathological Pregnancymentioning

confidence: 89%

Glycolysis: A fork in the path of normal and pathological pregnancy

Gou,

Zhang

2023

The FASEB Journal

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Glucose metabolism is vital to the survival of living organisms. Since the discovery of the Warburg effect in the 1920s, glycolysis has become a major research area in the field of metabolism. Glycolysis has been extensively studied in the field of cancer and is considered as a promising therapeutic target. However, research on the role of glycolysis in pregnancy is limited. Recent evidence suggests that blastocysts, trophoblasts, decidua, and tumors all acquire metabolic energy at specific stages in a highly similar manner. Glycolysis, carefully controlled throughout pregnancy, maintains a dynamic and coordinated state, so as to maintain the homeostasis of the maternal–fetal interface and ensure normal gestation. In the present review, we investigate metabolic remodeling and the selective propensity of the embryo and placenta for glycolysis. We then address dysregulated glycolysis that occurs in the cellular interactive network at the maternal–fetal interface in miscarriage, preeclampsia, fetal growth restriction, and gestational diabetes mellitus. We provide new insights into the field of maternal–fetal medicine from a metabolic perspective, thus revealing the mystery of human pregnancy.

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“…So far, the only and most reliable treatment for PE is delivery, but the pathogenesis of PE is still an enigma. About the pathogenesis, two-stage theory is now widely accepted: In stage I, during embryogenesis, trophoblast invasion of the uterine myometrium is inadequate and the uterine spiral artery remodeling is impaired, which leads toplacental ischemia and hypoxiametabolism disorder; In stage II, the presence of a large number of undesirable factors in the maternal blood leads to a systemic inflammatory response and vascular endothelial dysfunction in the maternal body, which eventually results in PE (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Dysfunction of Decidual Macrophages Is a Potential Risk Factor in the Occurrence of Preeclampsia

et al. 2021

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Preeclampsia is a multi-factorial and multi-genetic disorder that affects more than eight million mother and baby pairs each year. Currently, most of the attention to the pathogenesis of preeclampsia has been focused on placenta, but recent progresses suggest that excellent decidualization lays foundation for placentation and growth. Moreover, preeclampsia is associated with an imbalance in immunoregulatory mechanisms, however, how the immune regulatory system in the decidua affects preeclampsia is still unclear. In our study, after intersecting the genes of differentially expressed between preeclampsia and the control gotten by conventional expression profile analysis and the genes contained in the ligand receptor network, we found eight differentially expressed genes in a ligand-receptor relationship, and the eight genes have a characteristic: most of them participate in the interaction between decidual macrophages and other decidual immune cells. The results of single-cell sequencing of decidual cells further demonstrated that decidual macrophages affect the functions of other immune cells through export. As a result, abnormal gene expression affects the export function of decidual macrophages, which in turn affects the interaction of decidual macrophages with other immune cells, thereby destroying the original immune regulation mechanism, and ultimately leading to the occurrence of preeclampsia.

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Increased expression and phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoforms in urinary exosomes in pre-eclampsia

Cited by 22 publications

References 38 publications

HIF-1/AKT Signaling-Activated PFKFB2 Alleviates Cardiac Dysfunction and Cardiomyocyte Apoptosis in Response to Hypoxia

HIF-1/AKT Signaling-Activated PFKFB2 Alleviates Cardiac Dysfunction and Cardiomyocyte Apoptosis in Response to Hypoxia

Glycolysis: A fork in the path of normal and pathological pregnancy

Dysfunction of Decidual Macrophages Is a Potential Risk Factor in the Occurrence of Preeclampsia

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