+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

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

, : Heat shock protein 70 regulates platelet integrin activation, granule secretion and aggregation. American Journal of Physiology. Cell Physiology 310(7): C568-C575

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 shear. Biochemical studies supported a role for Hsp70 in maintaining the assembly of the linker for activation of T cells signalosome, which couples GPVI-initiated signaling to integrin activation, secretion, and platelet function. Together, our results suggest that Hsp70 regulates platelet activation and function by supporting linker for activation of T cells-associated signaling events downstream of platelet GPVI engagement, suggesting a role for Hsp70 in the intracellular organization of signaling systems that mediate platelet secretion, "inside-out" activation of platelet integrin-αIIbβ3, platelet-platelet aggregation, and, ultimately, hemostatic plug and thrombus formation.


PMID: 26764050

DOI: 10.1152/ajpcell.00362.2015

Other references

Eckhardt Engelhardt August, 1940: Partnership between geology and geophysics in prospecting for oil. Geophysics 5(3, Part 1): 209-214

Lefkowitz, M.M.; Cannon, J., 1966: Physique and obstreperous behavior. Journal of Clinical Psychology 22(2): 172-174

Scharf, M.B.; Brown, D.; Woods, M.; Brown, L.; Hirschowitz, J., 1985: The effects and effectiveness of gamma-hydroxybutyrate in patients with narcolepsy. Thirty patients with polysomnographically confirmed narcolepsy were treated with GHB (gamma-hydroxybutyrate) for up to 30 weeks. The number of nightly awakenings significantly decreased, while Stages 3 and 4 sleep substantially increased. The clin...

Maurice, T.; Mustafa, M-Hariri.; Desrumaux, C.; Keller, E.; Naert, Gëlle.; de la C García-Barceló, Mía.; Rodríguez Cruz, Y.; Garcia Rodríguez, Jío.César., 2014: Intranasal formulation of erythropoietin (EPO) showed potent protective activity against amyloid toxicity in the Aβ₂₅₋₃₅ non-transgenic mouse model of Alzheimer's disease. Erythropoietin (EPO) promotes neurogenesis and neuroprotection. We here compared the protection induced by two EPO formulations in a rodent model of Alzheimer's disease (AD): rHu-EPO and a low sialic form, Neuro-EPO. We used the intracerebrov...

Delcour, A.; Peters, J-L.; Lancellotti, P., 2014: Image of the month. Pulmonary sequestration. Revue Medicale de Liege 68(9): 433-435

Zajic, L.B.; Herndon, A.K.; Sieberg, L.G.; Caress, A.L.; Morgan, P.K.; Hansen, R.J.; Wittenburg, L.A.; Gustafson, D.L.; Quimby, J.M., 2017: Assessment of absorption of transdermal ondansetron in normal research cats. Objectives The objective of this study was to assess the absorption of transdermal ondansetron in healthy cats. Methods Five research cats with unremarkable complete blood count, biochemistry and urinalysis were used for both single- and multiple-...

Tanaka, Y.; Mizote, H.; Inada, H.; Motohiro, T.; Kobayashi, H.; Fukahori, S.; So, H.; Otani, M.; Nakamizo, H.; Asagiri, K.; Akiyoshi, K.; Tsuru, T.; Hikida, S., 2004: Efficacy of n-3 polyunsaturated fatty acid enriched enteral nutrient solution in relieving oxidative stress in patients with severe psychophysiologic disorders. It is not unusual for patients with severe motor and intellectual disabilities to present with eating and swallowing disorders, and such patients often require long term enteral nutrition. These patients tend to receive all their nutrients in the...

Schacknow, P.N.; Raab, D.H., 1976: Noise intensity discrimination effects of bandwidth conditions and mode of masker presentation. Noise-intensity discrimination [in human subjects] was studied as a function of both signal and masker bandwidth. Five bandwidths of noise, ranging from 100-10,000 Hz, were employed. Maskers were presented at each of 3 spectrum levels (5, 25 and 4...

Quinn C.M.; Wigglesworth J.S.; Heckmatt J., 1991: Lethal arthrogryposis multiplex congenita a pathological study of 21 cases. Twenty-one cases of arthrogryposis multplex congenita, which had resulted in death soon after birth or had been aborted following prenatal diagnosis, were studied. Histochemical and histological study of muscle indicated that 11 cases were of myog...

Borregaard N., 1975: Regulation of d to l conversion of glycogen synthetase of human polymorphonuclear leukocytes. Res Journal Of The Reticuloendothelial Societyppl: 11a