Facilitated Phosphatidylserine (PS) Flip-Flop and Thrombin Activation Using A Synthetic PS Scramblase

Boon, J. Middleton; Lambert, Timothy N.; Sisson, Adam L.; Davis, and Anthony P.; Smith, Bradley D.

doi:10.1021/ja029670q

Cited by 53 publications

(46 citation statements)

References 31 publications

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“…However, previous work has shown that 12 can mediate the translocation of phosphatidylserine head groups in vesicles, and that the corresponding eicosyl ester is equally active. [17] By the argument used previously, this strongly suggests that 12 and (presumably) 13 locate within the membrane. The most likely explanation for their low chloride transport activity is the formation of extremely stable electroneutral complexes [25] which only slowly release anions into the aqueous phase.…”

Section: Transport By Cholapods Pre-incorporated In Vesicle Membranesmentioning

confidence: 68%

Structure–Activity Relationships in Cholapod Anion Carriers: Enhanced Transmembrane Chloride Transport through Substituent Tuning

McNally¹,

Koulov²,

Lambert³

et al. 2008

Chemistry A European J

117

111

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Chloride transport by a series of steroid-based "cholapod" receptors/carriers was studied in vesicles. The principal method involved preincorporation of the cholapods in the vesicle membranes, and the use of lucigenin fluorescence quenching to detect inward-transported Cl − . The results showed a partial correlation between anion affinity and transport activity, in that changes at the steroidal 7 and 12 positions affected both properties in concert. However, changes at the steroidal 3-position yielded irregular effects. Among the new steroids investigated the bis-p-nitrophenylthiourea 3 showed unprecedented activity, giving measurable transport through membranes with a transporter/lipid ratio of 1:250 000 (an average of <2 transporter molecules per vesicle). Increasing transporter lipophilicity had no effect, and positively charged steroids had low activity. The p-nitrophenyl monourea 25 showed modest but significant activity. Measurements using a second method, requiring the addition of transporters to preformed vesicle suspensions, implied that transporter delivery was problematic in some cases. A series of measurements employing membranes of different thicknesses provided further evidence that the cholapods act as mobile anion carriers.

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Section: Transport By Cholapods Pre-incorporated In Vesicle Membranesmentioning

confidence: 68%

Structure–Activity Relationships in Cholapod Anion Carriers: Enhanced Transmembrane Chloride Transport through Substituent Tuning

McNally¹,

Koulov²,

Lambert³

et al. 2008

Chemistry A European J

117

111

View full text Add to dashboard Cite

show abstract

“…It is, however, possible that DEHP has a non-specific effect with regard to lipid flip-flop and that other lipids also have increased transverse movement after RBCs are exposed to DEHP. The effect in which stomatocyte formation is seen simultaneously with appearance of exposed PS, has been seen elsewhere, with the addition of nanoparticles to RBCs [42]; small molecules have also been shown previously to be able to cause lipid flip-flop between leaflets [43,44]. …”

Section: Discussionmentioning

confidence: 89%

The Blood Bag Plasticizer Di-2-Ethylhexylphthalate Causes Red Blood Cells to Form Stomatocytes, Possibly by Inducing Lipid Flip-Flop

Melzak

Uhlig

Kirschhöfer

et al. 2018

Transfus Med Hemother

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Background: During storage of red blood cell (RBC) concentrates, the plasticizer di-2-ethylhexylphthalate (DEHP) that keeps the blood bags soft leaches out and can be taken up by the RBCs. DEHP is known to be beneficial for the RBC storage quality, but the molecular mechanisms of the action are unknown. Methods: Aqueous suspensions of DEHP were added to RBCs in buffer. The morphological effects were observed on RBCs from 5 donors. Flow cytometry with annexin A5 binding was used to measure the exposed phosphatidylserine. Results: DEHP induced the formation of stomatocytes at concentrations as low as ng/ml, provided that the cell suspension was also sufficiently dilute. Some spherocytes, which were susceptible to lysis, were also formed; after lysis, RBC ghosts were seen to continue the transition to the cup-shaped stomatocyte form. Incubation with DEHP increased the exposed phosphatidylserine, an effect that was also observed in the presence of vanadate, which inhibits the ATP-dependent translocases that maintain the membrane's lipid asymmetry. Conclusions: DEHP can have an active effect on RBC shape, instead of just preventing the storage-related shape changes. The effect appears to be mediated by increased flip-flop of lipids between the leaflets of the RBC membrane.

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“…In this tissue, thrombin is synthesized by muscle cells [12] and acts locally by contributing to synapse remodeling and elimination at the neuromuscular junction [54,101] but plays also an essential role in muscle cell differentiation [11,89]. A prerequisite for the activation of thrombin at the neuromuscular junction is the local externalization of phosphatidylserine phospholipids, which contribute to the binding of thrombin activator complex to the membrane [9].…”

Section: Muscle Antithrombin III (At-iii) or Bovserpinc1mentioning

confidence: 99%

Caspases and Thrombin Activity Regulation by Specific Serpin Inhibitors in Bovine Skeletal Muscle

Gagaoua

Hafid

Boudida

et al. 2015

Appl Biochem Biotechnol

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In living cells, after activation, protein inhibitors constitute the last step of proteases activity regulation. This review intends to provide original information about a group of bovine muscle serine proteases inhibitors belonging to the Serpin superfamily and characterized at the gene and protein level. This report is the only one and the first to provide much information on this group of proteases inhibitors of the serpin type and their potential biological functions. Amongst the eight genes identified in bovine, three serpins were purified from the muscle tissue and characterized. These are two members of the bovSERPINA3 family, i.e., bovSERPINA3-1 and A3-3, and the last one is antithrombin III (AT-III or BovSERPINC1). BovSERPINA3 family comprises at least eight protein members encoded by different genes mapped on chromosome 7q23-q26 cluster. BovSERPINA3-1 and A3-3 were shown to locate within muscle cells and are cross-class inhibitors strongly active against trypsin as well as against human initiator and effector caspases 8 and 3. They constitute a key apoptosis control in mammals. They were thus expressed in proliferating and confluent myoblasts phases where cells must be alive but not in myotubes. Antithrombin III inhibits trypsin and, in a heparin dependent manner, thrombin. AT-III and its mRNA were expressed in muscle cells and in differentiating primary myoblasts in culture.

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Facilitated Phosphatidylserine (PS) Flip-Flop and Thrombin Activation Using A Synthetic PS Scramblase

Cited by 53 publications

References 31 publications

Structure–Activity Relationships in Cholapod Anion Carriers: Enhanced Transmembrane Chloride Transport through Substituent Tuning

Structure–Activity Relationships in Cholapod Anion Carriers: Enhanced Transmembrane Chloride Transport through Substituent Tuning

The Blood Bag Plasticizer Di-2-Ethylhexylphthalate Causes Red Blood Cells to Form Stomatocytes, Possibly by Inducing Lipid Flip-Flop

Caspases and Thrombin Activity Regulation by Specific Serpin Inhibitors in Bovine Skeletal Muscle

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