Modulation of Prothrombinase Assembly and Activity by Phosphatidylethanolamine

Majumder, Rinku; Liang, Xiao; Quinn-Allen, Mary Ann; Kane, William H.; Lentz, Barry R.

doi:10.1074/jbc.m111.260141

Cited by 23 publications

(20 citation statements)

References 43 publications

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“…Phosphatidylethanolamine (PE) is a class of phospholipids found in biofilms that make up 25% of all phospholipids and are important precursors, substrates and donors in multiple biological pathways (Vance & Tasseva, ; Wellner, Diep, Janfelt, & Hansen, ). Studies have shown that, in the process of blood coagulation, PE and phosphatidylserine can increase the rate of formation of thrombin and promote blood coagulation by promoting the binding with coagulation factors (Majumder, Liang, Quinn‐Allen, Kane, & Lentz, ). Compared with the NC group, the levels of phosphorylcholine, PC, PE and LysoPC in BSS group were significantly increased (Figure ), indicating that glycerophospholipid metabolism was disrupted in BSS rats and this result is consistent with the findings of Han et al ().…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Metabolomics study on promoting blood circulation and ameliorating blood stasis: Investigating the mechanism of Angelica sinensis and its processed products

Yuan

Zhong

Hua

et al. 2019

Biomedical Chromatography

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Angelica sinensis (Danggui, DG) parched with alcohol (Jiu Danggui, JDG) and charred DG are the main processed products of DG, which are used to treat blood stasis syndrome (BSS). However, their therapeutic effect and mechanisms are still unclear. Based on an acute rat BSS model, the intervention effects of DG and its processed products (DGPPs) were evaluated by the hemorheology and coagulation function parameters. Meanwhile, plasma and urine metabolites were detected and analyzed by liquid chromatography coupled to quadrupole time‐of‐flight mass spectrometry and multivariate statistical analysis method. The results of hemorheology, coagulation function parameters and metabolomics all showed that the BSS model was successfully established, DGPPs intervention could significantly relieve rats BSS and the therapeutic effect of JDG was best. Moreover, 23 differential metabolites (14 in plasma and nine in urine) were identified that were closely related to the BSS, involving seven potential target metabolic pathways. DGPP intervention showed different degrees of reverse effect on these metabolites. JDG was the most effective owing to extensive regulation effect on differential metabolites. This study provides a reference for understanding the pathological mechanism of BSS and the mechanism of DGPPs, which lays a theoretical foundation for the rational use of DGPPs in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Metabolomics study on promoting blood circulation and ameliorating blood stasis: Investigating the mechanism of Angelica sinensis and its processed products

Yuan

Zhong

Hua

et al. 2019

Biomedical Chromatography

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“…125,[136][137][138] In addition to PS, the anionic PE has also been shown to bind coagulation factor Va with a high affinity (*10 nM kDa) and promote thrombin generation. 139 Despite strong circumstantial clinical and laboratory evidence, the role of brain-derived phospholipids in the development of TBIassociated coagulopathy remains unknown. Phospholipids released from injured neural cells, are also highly susceptible to oxidation.…”

Section: Phosphatidylserine and Brain Phospholipidsmentioning

confidence: 99%

Traumatic Brain Injury-Associated Coagulopathy

Zhang

Jiang

Liu

et al. 2012

Journal of Neurotrauma

129

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Traumatic injury is a common cause of coagulopathy, primarily due to blood loss and hemodilution secondary to fluid resuscitation. Traumatic injury-associated coagulopathy often follows a course of transition from hyper- to hypocoagulable state exemplified in disseminated intravascular coagulation. The incidence of coagulopathy is significantly higher in patients with traumatic brain injury (TBI), especially those with penetrating trauma compared to injury to the trunk and limbs. This occurs despite the fact that patients with isolated TBI bleed less and receive restricted volume load of fluids. TBI-associated coagulopathy is extensively documented to associate with poor clinical outcomes, but its pathophysiology remains poorly understood. Studies in the past have shown that brain tissue is highly enriched in key procoagulant molecules. This review focuses on the biochemical and cellular characteristics of these molecules and pathways that could make brain uniquely procoagulant and prone to coagulopathy. Understanding this unique procoagulant environment will help to identify new therapeutic targets that could reverse a state of coagulopathy with minimal impacts on hemostasis, a critical requirement for neurosurgical treatments of TBI.

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“…While PS is the most significant phospholipid that regulates the structure and function of coagulation proteins such as fXa, fIXa, and fVa [ 12 – 14 ], other phospholipids also play crucial roles in coagulation. PE, another phospholipid abundant in activated platelet, was reported to modulate APC-mediated inactivation of fVa [ 15 ], promote the assembly and activity of the prothrombinase (fXa-fVa) complex [ 16 ], and regulate the structure and activity of fVIIa [ 17 ], (unpublished data). Again, fVIIa and activated protein C (APC) were reported to preferentially bind to nanobilayers containing PA [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Phosphatidylserine and Phosphatidylethanolamine Bind to Protein Z Cooperatively and with Equal Affinity

Sengupta

2016

PLoS ONE

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Protein Z (PZ) is an anticoagulant that binds with high affinity to Protein Z-dependent protease inhibitor (ZPI) and accelerates the rate of ZPI-mediated inhibition of factor Xa (fXa) by more than 1000-fold in the presence of Ca2+ and phospholipids. PZ promotion of the ZPI-fXa interaction results from the anchoring of the Gla domain of PZ onto phospholipid surfaces and positioning the bound ZPI in close proximity to the Gla-anchored fXa, forming a ternary complex of PZ/ZPI/fXa. Although interaction of PZ with phospholipid membrane appears to be absolutely crucial for its cofactor activity, little is known about the binding of different phospholipids to PZ. The present study was conceived to understand the interaction of different phospholipids with PZ. Experiments with both soluble lipids and model membranes revealed that PZ binds to phosphatidylserine (PS) and phosphatidylethanolamine (PE) with equal affinity (Kd~48 μM); further, PS and PE bound to PZ synergistically. Equilibrium dialysis experiments revealed two lipid-binding sites for both PS and PE. PZ binds with weaker affinity to other phospholipids, e.g., phosphatidic acid, phosphatidylglycerol, phosphatidylcholine and binding of these lipids is not synergistic with respect to PS. Both PS and PE -containing membranes supported the formation of a fXa-PZ complex. PZ protection of fXa from antithrombin inhibition were also shown to be comparable in presence of both PS: PC and PE: PC membranes. These findings are particularly important and intriguing since they suggest a special affinity of PZ, in vivo, towards activated platelets, the primary membrane involved in blood coagulation process.

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Modulation of Prothrombinase Assembly and Activity by Phosphatidylethanolamine

Cited by 23 publications

References 43 publications

Metabolomics study on promoting blood circulation and ameliorating blood stasis: Investigating the mechanism of Angelica sinensis and its processed products

Metabolomics study on promoting blood circulation and ameliorating blood stasis: Investigating the mechanism of Angelica sinensis and its processed products

Traumatic Brain Injury-Associated Coagulopathy

Phosphatidylserine and Phosphatidylethanolamine Bind to Protein Z Cooperatively and with Equal Affinity

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