Molecular mapping of platelet hyperreactivity in diabetes: the stress proteins complex HSPA8/Hsp90/CSK2α and platelet aggregation in diabetic and normal platelets.
Adult
Aged
Blood Platelets
/ physiology
CSK Tyrosine-Protein Kinase
/ physiology
Diabetes Mellitus
/ blood
Female
HSC70 Heat-Shock Proteins
/ antagonists & inhibitors
HSP90 Heat-Shock Proteins
/ antagonists & inhibitors
Humans
Male
Middle Aged
Platelet Aggregation
Platelet Membrane Glycoproteins
/ analysis
2DE
BM
CFT
CSK2α
CT
CVD
HSPA8
Hsp90
IPA
LOESS
MALDI-TOF
MCF
MS
PMF
PP1Cɣ
PRP
RT
bone marrow
cardiovascular disease
casein kinase 2α
clot formation time
clotting time
heat shock protein A8
heat shock protein90
induced platelet aggregation
local regression model
mass spectrometry
matrix-assisted laser desorption/ionization time-of-flight
maximum clot firmness
peptide mass fingerprinting
platelet-rich plasma
protein phosphatase 1Cɣ
room temperature
two-dimensional electrophoresis
Journal
Translational research : the journal of laboratory and clinical medicine
ISSN: 1878-1810
Titre abrégé: Transl Res
Pays: United States
ID NLM: 101280339
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
01
12
2020
revised:
09
04
2021
accepted:
12
04
2021
pubmed:
23
4
2021
medline:
14
8
2021
entrez:
22
4
2021
Statut:
ppublish
Résumé
The molecular understanding of the pathophysiological changes elicited by diabetes in platelets may help in further elucidating the involvement of this pseudo-cell in the increased risk of developing cardiovascular disease and thrombosis in diabetic subjects. We aimed to investigate the differential characteristics of platelets from diabetic patients and nondiabetic controls to unveil the molecular mechanisms behind the increased platelet reactivity in diabetes. We compared platelets from diabetic and control subjects by 2 dimensional-electrophoresis followed by mass spectrometry. Changes in selected differential proteins were validated by immunoprecipitation assays and western blot. Platelet aggregation was measured by light transmittance aggregometry induced by collagen and ADP, and dynamic coagulation analysis of whole blood was measured by thromboelastometry. We observed significant differences in proteins related to platelet aggregation, cell migration, and cell homeostasis. Subjects with diabetes showed higher platelet aggregation and thrombogenicity and higher contents of the stress-related protein complex HSPA8/Hsp90/CSK2α than nondiabetic subjects. Changes in the chaperones HSPA8 and Hsp90, and in CSK2α protein contents correlated with changes in platelet aggregation and blood coagulation activity. In conclusion, the complex HSPA8/Hsp90/CSK2α is involved in diabetes-related platelet hyperreactivity. The role of the HSPA8/Hsp90/CSK2α complex may become a molecular target for the development of future preventive and therapeutic strategies for platelet dysfunction associated with diabetes and its complications.
Identifiants
pubmed: 33887528
pii: S1931-5244(21)00085-2
doi: 10.1016/j.trsl.2021.04.003
pii:
doi:
Substances chimiques
HSC70 Heat-Shock Proteins
0
HSP90 Heat-Shock Proteins
0
HSPA8 protein, human
0
Platelet Membrane Glycoproteins
0
CSK Tyrosine-Protein Kinase
EC 2.7.10.2
CSK protein, human
EC 2.7.10.23
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-14Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.