One inositol ring to rule thrombosis

Morrissey, James H.

doi:10.1182/blood-2013-07-511006

Cited by 2 publications

(1 citation statement)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inositol Hexakisphosphate Kinase Regulate Extracellular Polyphosphate Accumulation-Inositol hexakisphosphate kinase (IP6K) uses IP6 as a substrate to generate the inositol pyrophosphates IP7 and IP8 (37,38). Yeast lacking the IP6K Kcs1 have no observable polyphosphate accumulation (14,16).…”

Section: Resultsmentioning

confidence: 99%

Extracellular Polyphosphate Inhibits Proliferation in an Autocrine Negative Feedback Loop in Dictyostelium discoideum

Suess

Gomer

2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Polyphosphate is a polymer of phosphate residues linked by high energy phosphoanhydride bonds. Despite being highly conserved throughout nature, its function is poorly understood. Here we show that Dictyostelium cells accumulate extracellular polyphosphate, and this acts to inhibit proliferation at high cell densities. In shaking culture, extracellular polyphosphate concentrations increase as cell density increases, and if the concentration of polyphosphate observed at the stationary phase is added to cells at mid-log, proliferation is halted. Adding an exopolyphosphatase to cell cultures or stationary phase conditioned medium decreases polyphosphate levels and abrogates the anti-proliferative effect. The cells show saturable binding of polyphosphate, suggesting the presence of a cell surface polyphosphate receptor. Extracellular polyphosphate accumulation is potentiated by decreased nutrient levels, potentially as a means to anticipate starvation. Loss of the Dictyostelium polyphosphate kinase DdPpk1 causes intracellular polyphosphate levels to become undetectable and negatively affects fitness, cytokinesis, and germination. However, cells lacking DdPpk1 accumulate ϳ50% normal levels of extracellular polyphosphate, suggesting an additional means of synthesis. We found that cells lacking inositol hexakisphosphate kinase, which is responsible for the synthesis of the inositol pyrophosphates IP7 and IP8, reach abnormally high cell densities and show decreased extracellular polyphosphate levels. Two different enzymes thus appear to mediate the synthesis of Dictyostelium extracellular polyphosphate, which is used as a signal in an autocrine negative feedback loop to regulate cell proliferation.

show abstract

Section: Resultsmentioning

confidence: 99%

Extracellular Polyphosphate Inhibits Proliferation in an Autocrine Negative Feedback Loop in Dictyostelium discoideum

Suess

Gomer

2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

Higher Plasma Myo-Inositol in Pregnancy Associated with Reduced Postpartum Blood Loss: Secondary Analyses of the NiPPeR Trial

Chang,

Yong,

Zhang

et al. 2024

Nutrients

View full text Add to dashboard Cite

We previously reported that a combined myo-inositol, probiotics, and enriched micronutrient supplement (intervention) taken preconception and in pregnancy reduced postpartum blood loss (PBL) and major postpartum hemorrhage compared with a standard micronutrient supplement (control), as secondary outcomes of the NiPPeR trial. This study aimed to identify the intervention components that may contribute to this effect. Associations of plasma concentrations of myo-inositol and vitamins B2, B6, B12, and D at preconception (before and after supplementation), early (~7-weeks), and late pregnancy (~28-weeks) with PBL were assessed by multiple linear regression, adjusting for site, ethnicity, preconception BMI, parity, and previous cesarean section. Amongst 583 women, a higher concentration of myo-inositol in early pregnancy was associated with a PBL reduction [βadj −1.26 (95%CI −2.23, −0.29) mL per µmol/L myo-inositol increase, p = 0.011]. Applying this co-efficient to the increase in mean 7-week-myo-inositol concentration of 23.4 µmol/L with the intervention equated to a PBL reduction of 29.5 mL (~8.4% of mean PBL of 350 mL among controls), accounting for 84.3% of the previously reported intervention effect of 35 mL. None of the examined vitamins were associated with PBL. Therefore, myo-inositol may be a key intervention component mediating the PBL reduction. Further work is required to determine the mechanisms involved.

show abstract

One inositol ring to rule thrombosis

Cited by 2 publications

References 10 publications

Extracellular Polyphosphate Inhibits Proliferation in an Autocrine Negative Feedback Loop in Dictyostelium discoideum

Extracellular Polyphosphate Inhibits Proliferation in an Autocrine Negative Feedback Loop in Dictyostelium discoideum

Higher Plasma Myo-Inositol in Pregnancy Associated with Reduced Postpartum Blood Loss: Secondary Analyses of the NiPPeR Trial

Contact Info

Product

Resources

About