Heat shock protein 70 regulates platelet integrin activation, granule secretion and aggregation

American Journal of Physiology. Cell Physiology
R A RiggJoseph E Aslan

Abstract

Molecular chaperones that support protein quality control, including heat shock protein 70 (Hsp70), participate in diverse aspects of cellular and physiological function. Recent studies have reported roles for specific chaperone activities in blood platelets in maintaining hemostasis; however, the functions of Hsp70 in platelet physiology remain uninvestigated. Here we characterize roles for Hsp70 activity in platelet activation and function. In vitro biochemical, microscopy, flow cytometry, and aggregometry assays of platelet function, as well as ex vivo analyses of platelet aggregate formation in whole blood under shear, were carried out under Hsp70-inhibited conditions. Inhibition of platelet Hsp70 blocked platelet aggregation and granule secretion in response to collagen-related peptide (CRP), which engages the immunoreceptor tyrosine-based activation motif-bearing collagen receptor glycoprotein VI (GPVI)-Fc receptor-γ chain complex. Hsp70 inhibition also reduced platelet integrin-αIIbβ3 activation downstream of GPVI, as Hsp70-inhibited platelets showed reduced PAC-1 and fibrinogen binding. Ex vivo, pharmacological inhibition of Hsp70 in human whole blood prevented the formation of platelet aggregates on collagen under shea...Continue Reading

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Citations

Mar 14, 2018·Platelets·Hind Hamzeh-CognasseFabrice Cognasse
Feb 6, 2020·Journal of Thrombosis and Haemostasis : JTH·Joseph W JacksonLeonard M Neckers
Dec 6, 2019·Medical and Veterinary Entomology·L LiuT-Y Cheng
Jul 10, 2019·Frontiers in Cardiovascular Medicine·Amanda Z Zucoloto, Craig N Jenne
Dec 19, 2020·Translational Oncology·Zarema AlbakovaAlexander M Sapozhnikov
Oct 28, 2018·Ticks and Tick-borne Diseases·Xiao-Ming HeTian-Yin Cheng
Apr 23, 2021·Translational Research : the Journal of Laboratory and Clinical Medicine·Gemma Chiva-BlanchLina Badimon
Jun 3, 2021·Biomolecules·Brandon Bautista-BecerrilAngel Camarena
Jul 5, 2021·Journal of Human Hypertension·Yobana Armenta-MedinaDoris Cerecedo
Aug 8, 2021·International Journal of Molecular Sciences·Théo EbermeyerHind Hamzeh-Cognasse

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