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A novel role for ph...
A novel role for phospholipase D as an endogenous negative regulator of platelet sensitivity
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- Elvers, Margitta (författare)
- Medizinische Klinik III, Dept. of Cardiology and Cardiovascular Diseases, Eberhard Karls University, Tübingen, Germany
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- Grenegård, Magnus, 1963- (författare)
- Linköpings universitet,Farmakologi,Hälsouniversitetet
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- Khoshjabinzadeh, Hanieh (författare)
- Linköpings universitet,Klinisk kemi,Hälsouniversitetet
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- Münzer, Patrick (författare)
- Department of Physiology, Eberhard Karls University, Tübingen, Germany
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- Borst, Oliver (författare)
- Medizinische Klinik III, Dept. of Cardiology and Cardiovascular Diseases, Eberhard Karls University, Tübingen, Germany; Department of Physiology, Eberhard Karls University, Tübingen, Germany
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- Tian, Huasong (författare)
- Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, USA,Columbia University, NY 10032 USA
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- Di Paolo, Gilbert (författare)
- Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, USA,Columbia University, NY 10032 USA
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- Lang, Florian (författare)
- Department of Physiology, Eberhard Karls University, Tübingen, Germany
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- Gawaz, Meinrad (författare)
- Medizinische Klinik III, Dept. of Cardiology and Cardiovascular Diseases, Eberhard Karls University, Tübingen, Germany
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- Lindahl, Tomas (författare)
- Östergötlands Läns Landsting,Linköpings universitet,Klinisk kemi,Hälsouniversitetet
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- Fälker, Knut (författare)
- Linköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet
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Medizinische Klinik III, Dept of Cardiology and Cardiovascular Diseases, Eberhard Karls University, Tübingen, Germany Farmakologi (creator_code:org_t)
- New York, USA : Elsevier, 2012
- 2012
- Engelska.
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Ingår i: Cellular Signalling. - New York, USA : Elsevier. - 0898-6568 .- 1873-3913. ; 24:9, s. 1743-52
- Relaterad länk:
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http://liu.diva-port...
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https://liu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- Platelet aggregation, secretion and thrombus formation play a critical role in primary hemostasis to prevent excessive blood loss. On the other hand, uncontrolled platelet activation leads to pathological thrombus formation resulting in myocardial infarction or stroke. Stimulation of heterotrimeric G-proteins by soluble agonists or immunoreceptor tyrosine based activation motif-coupled receptors that interact with immobilized ligands such as the collagen receptor glycoprotein (GP) VI lead to the activation of phospholipases that cleave membrane phospholipids to generate soluble second messengers. Platelets contain the phospholipases (PL) D1 and D2 which catalyze the hydrolysis of phosphatidylcholine to generate the second messenger phosphatidic acid (PA). The production of PA is abrogated by primary alcohols that have been widely used for the analysis of PLD-mediated processes. However, it is not clear if primary alcohols effectively reduce PA generation or if they induce PLD-independent cellular effects. In the present study we made use of the specific PLD inhibitor 5-fluoro-2-indolyl des-chlorohalopemide (FIPI) and show for the first time, that FIPI enhances platelet dense granule secretion and aggregation of human platelets. Further, FIPI has no effect on cytosolic Ca(2+) activity but needs proper Rho kinase signaling to mediate FIPI-induced effects on platelet activation. Upon FIPI treatment the phosphorylation of the PKC substrate pleckstrin was prominently enhanced suggesting that FIPI affects PKC-mediated secretion and aggregation in platelets. Similar effects of FIPI were observed in platelets from mouse wild-type and Pld1(-/-) mice pointing to a new role for PLD2 as a negative regulator of platelet sensitivity.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- PLD
- platelets
- secretion
- aggregation
- regulation
- MEDICINE
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Elvers, Margitta
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Grenegård, Magnu ...
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Khoshjabinzadeh, ...
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Münzer, Patrick
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Borst, Oliver
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Tian, Huasong
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Di Paolo, Gilber ...
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Lang, Florian
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Gawaz, Meinrad
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Lindahl, Tomas
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Fälker, Knut
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- Av lärosätet
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Örebro universitet
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Linköpings universitet