Superoxide Dismutase 2 is dispensable for platelet function

Trevor P Fidler; Jesse W Rowley; Claudia Araujo; Luc H Boudreau; Alex Marti; Rhonda Souvenir; Kali Dale; Eric Boilard; Andrew S Weyrich; E Dale Abel

doi:10.1160/TH17-03-0174

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Superoxide Dismutase 2 is dispensable for platelet function

Journal article

Open access

Peer reviewed

Superoxide Dismutase 2 is dispensable for platelet function

Trevor P Fidler, Jesse W Rowley, Claudia Araujo, Luc H Boudreau, Alex Marti, Rhonda Souvenir, Kali Dale, Eric Boilard, Andrew S Weyrich and E Dale Abel

Thrombosis and haemostasis, Vol.117(10), pp.1859-1867

10/05/2017

DOI: 10.1160/TH17-03-0174

PMCID: PMC5894334

PMID: 28771279

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Abstract

Increased intracellular reactive oxygen species (ROS) promote platelet activation. The sources of platelet-derived ROS are diverse and whether or not mitochondrial derived ROS, modulates platelet function is incompletely understood. Studies of platelets from patients with sickle cell disease, and diabetes suggest a correlation between mitochondrial ROS and platelet dysfunction. Therefore, we generated mice with a platelet specific knockout of superoxide dismutase 2 (SOD2-KO) to determine if increased mitochondrial ROS increases platelet activation. SOD2-KO platelets demonstrated decreased SOD2 activity and increased mitochondrial ROS, however total platelet ROS was unchanged. Mitochondrial function and content were maintained in non-stimulated platelets. However SOD2-KO platelets demonstrated decreased mitochondrial function following thrombin stimulation. In vitro platelet activation and spreading was normal and in vivo, deletion of SOD2 did not change tail-bleeding or arterial thrombosis indices. In pathophysiological models mediated by platelet-dependent immune mechanisms such as sepsis and autoimmune inflammatory arthritis, SOD2-KO mice were phenotypically identical to wildtype controls. These data demonstrate that increased mitochondrial ROS does not result in platelet dysfunction.

Phenotype

Mitochondria - enzymology

Superoxide Dismutase - genetics

Superoxide Dismutase - blood

Blood Platelets - enzymology

Arthritis - genetics

Thrombin - pharmacology

Time Factors

Thrombosis - blood

Blood Platelets - drug effects

Disease Models, Animal

Reactive Oxygen Species - blood

Mice, Inbred C57BL

Thrombosis - enzymology

Arthritis - blood

Genotype

Superoxide Dismutase - deficiency

Arthritis - enzymology

Sepsis - genetics

Mice, Knockout

Animals

Carotid Artery Diseases - enzymology

Platelet Activation

Sepsis - enzymology

Blood Platelets - ultrastructure

Carotid Artery Diseases - blood

Carotid Artery Diseases - genetics

Thrombosis - genetics

Sepsis - blood

Details

Title: Subtitle: Superoxide Dismutase 2 is dispensable for platelet function
Creators: Trevor P Fidler
Jesse W Rowley
Claudia Araujo
Luc H Boudreau
Alex Marti
Rhonda Souvenir
Kali Dale
Eric Boilard
Andrew S Weyrich
E Dale Abel - E. Dale Abel, MB.BS., DPhil., Fraternal Order of Eagles Diabetes Research Center, Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, 4312 PBDB, 169 Newton Road, Iowa City, IA 52242-1101, USA, Tel.: +1 353 3050, Fax: +1 335 3865, E-mail: DRCadmin@uiowa.edu
Resource Type: Journal article
Publication Details: Thrombosis and haemostasis, Vol.117(10), pp.1859-1867
DOI: 10.1160/TH17-03-0174
PMID: 28771279
PMCID: PMC5894334
NLM abbreviation: Thromb Haemost
ISSN: 0340-6245
eISSN: 2567-689X
Publisher: Germany
Grant note: T32 DK091317 / NIDDK NIH HHS R01 HL126547 / NHLBI NIH HHS T32 HL007344 / NHLBI NIH HHS K01 GM103806 / NIGMS NIH HHS F32 HL128008 / NHLBI NIH HHS U54 HL112311 / NHLBI NIH HHS
Language: English
Date published: 10/05/2017
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984025258002771

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