Inducing mitophagy in diabetic platelets protects against severe oxidative stress
Abstract
Synopsis
Introduction
Results
DM platelet oxidative stress is associated with p53 phosphorylation, mitochondrial dysfunction, and apoptosis
Mitophagy is induced in DM platelets
Mitophagy is induced in platelets through an oxidative stress‐induced JNK pathway
Mitophagy induction protects human platelets from increased oxidative stress
Mitophagy induction protects murine platelets from increased oxidative stress, platelet apoptosis, and thrombosis
Model of protection from oxidative stress‐induced apoptosis and thrombosis by induced mitophagy
Discussion
Protective role of mitophagy in DM platelets
Regulation of mitophagy in DM platelets
Materials and Methods
Preparation of human platelets
Measurement of mitochondrial membrane potential (∆Ψm), phosphatidylserine externalization through flow cytometry analysis
Immunocytochemistry and confocal microscopy
MitoTracker staining
Image analysis
Electron microscopy (EM) and immuno‐EM
Western blot analysis
Measurement of reactive oxidative stress (ROS)
Plateletlike particle (PLP) isolation from cultured human megakaryocytes (Meg‐01 cells)
Preparation of mouse platelets
Measurement of autophagy using flow cytometry analysis
Determination of platelet activation
Ferric chloride (FeCl3)‐induced carotid artery thrombosis model
Mice tail bleeding time
Human and mouse studies ethics statement
Statistics
Author contributions
Conflict of interest
Acknowledgements
Supporting Information
References
Information & Authors
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Cover: This month's cover highlights the Research Article “A novel thermoregulatory role for PDE10A in mouse and human adipocytes” by Mohammed K Hankir, Wiebke K Fenske and colleagues. They find that a PDE10A inhibitor causes weight loss and improves insulin sensitivity in obese mice associated with “browning” of white adipose tissue, and that it induces a thermogenic program in both human brown and white adipocytes. Scientific image by Prof. John Seibyl of Molecular Neuroimaging LLC, New Haven, CT, USA.
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