Skip to main content
SpringerLink
Log in

Heat Shock Protein 70 (Hsp70) in the Regulation of Platelet Function

  • Chapter
  • First Online:
Regulation of Heat Shock Protein Responses

Part of the book series: Heat Shock Proteins ((HESP,volume 13))

Abstract

Heat shock protein 70 (Hsp70) and its family of molecular chaperones are critical mediators of protein folding, trafficking, and control. Platelets are known to express several members of the Hsp70 family at high levels, suggesting critical roles for Hsp70 in platelet function. Several studies have described Hsp70-associated activities in intracellular signaling events, including the regulation of the linker for activation of T cells (LAT) signalosome that initiates integrin conformational changes underlying platelet aggregation. Although other chaperones perform established extracellular functions on the platelet surface as well as in the circulation to mediate the activities of platelets and other hematopoietic cells in hemostasis, thrombosis, and inflammation, similar roles for Hsp70 in platelet regulation remain undefined. Given the extensive roles of Hsp70 in many platelet-related human disease states, from protective roles in cardiovascular disease and wound healing to pathological roles in cancer, inflammation, and metabolic diseases, the emerging importance of Hsp70 in platelet function offers numerous ramifications for human health and disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ADP:

Adenosine diphosphate

APC:

Activated protein C

ATP:

Adenosine triphosphate

CLEC:

C-type lectin

CRP:

Collagen-related peptide

ER:

Endoplasmic reticulum

GPCR:

G-protein coupled receptor

GPVI:

Glycoprotein VI

Grp:

Glucose-regulated protein

GTP:

Guanosine triphosphate

Hsp:

Heat shock protein

ILK:

Integrin-linked kinase

LAT:

Linker for activation of T cells

NEF:

Nucleotide exchange factor

PAR:

Protease-activated receptor

PDI:

Protein disulfide isomerase

PGI2 :

Prostacyclin

PLC:

Phospholipase C

RAGE:

Receptor for advanced glycation endproducts

TLR:

Toll-like receptor

TRAP-6:

Thrombin receptor-activating peptide-6

TXA2 :

Thromboxane A2

References

  • Allende, M., Molina, E., Guruceaga, E., Tamayo, I., Gonzalez-Porras, J. R., Gonzalez-Lopez, T. J., Toledo, E., Rabal, O., Ugarte, A., Roldan, V., Rivera, J., Oyarzabal, J., Montes, R., & Hermida, J. (2016). Hsp70 protects from stroke in atrial fibrillation patients by preventing thrombosis without increased bleeding risk. Cardiovascular Research, 110, 309–318.

    Article  CAS  PubMed  Google Scholar 

  • Allende, M., Molina, E., Lecumberri, R., Sanchez-Arias, J. A., Ugarte, A., Guruceaga, E., Oyarzabal, J., & Hermida, J. (2017). Inducing heat shock protein 70 expression provides a robust antithrombotic effect with minimal bleeding risk. Thrombosis and Haemostasis, 117, 1722.

    Article  PubMed  Google Scholar 

  • Anand, P. K. (2010). Exosomal membrane molecules are potent immune response modulators. Communicative & Integrative Biology, 3, 405–408.

    Article  CAS  Google Scholar 

  • Asea, A., Kraeft, S. K., Kurt-Jones, E. A., Stevenson, M. A., Chen, L. B., Finberg, R. W., Koo, G. C., & Calderwood, S. K. (2000). HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nature Medicine, 6, 435–442.

    Article  CAS  PubMed  Google Scholar 

  • Asea, A., Rehli, M., Kabingu, E., Boch, J. A., Bare, O., Auron, P. E., Stevenson, M. A., & Calderwood, S. K. (2002). Novel signal transduction pathway utilized by extracellular HSP70: Role of toll-like receptor (TLR) 2 and TLR4. The Journal of Biological Chemistry, 277, 15028–15034.

    Article  CAS  PubMed  Google Scholar 

  • Aslam, R., Speck, E. R., Kim, M., Crow, A. R., Bang, K. W., Nestel, F. P., Ni, H., Lazarus, A. H., Freedman, J., & Semple, J. W. (2006). Platelet toll-like receptor expression modulates lipopolysaccharide-induced thrombocytopenia and tumor necrosis factor-alpha production in vivo. Blood, 107, 637–641.

    Article  CAS  PubMed  Google Scholar 

  • Aslan, J. E. (2017). Platelet shape change. In P. Gresele, N. S. Kleiman, J. A. Lopez, & C. P. Page (Eds.), Platelets in thrombotic and non-thrombotic disorders: Pathophysiology, pharmacology and therapeutics: An update (pp. 321–336). Cham: Springer.

    Chapter  Google Scholar 

  • Aslan, J. E., Itakura, A., Gertz, J. M., & McCarty, O. J. (2012). Platelet shape change and spreading. Methods in Molecular Biology, 788, 91–100.

    Article  CAS  PubMed  Google Scholar 

  • Aslan, J. E., Rigg, R. A., Nowak, M. S., Loren, C. P., Baker-Groberg, S. M., Pang, J., David, L. L., & McCarty, O. J. (2015). Lysine acetyltransfer supports platelet function. Journal of Thrombosis and Haemostasis, 13, 1908–1917.

    Article  CAS  PubMed  Google Scholar 

  • Assimon, V. A., Gillies, A. T., Rauch, J. N., & Gestwicki, J. E. (2013). Hsp70 protein complexes as drug targets. Current Pharmaceutical Design, 19, 404–417.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Atalay, M., Oksala, N., Lappalainen, J., Laaksonen, D. E., Sen, C. K., & Roy, S. (2009). Heat shock proteins in diabetes and wound healing. Current Protein & Peptide Science, 10, 85–95.

    Article  CAS  Google Scholar 

  • Bellaye, P. S., Burgy, O., Causse, S., Garrido, C., & Bonniaud, P. (2014). Heat shock proteins in fibrosis and wound healing: Good or evil? Pharmacology & Therapeutics, 143, 119–132.

    Article  CAS  Google Scholar 

  • Bertolotti, A., Zhang, Y., Hendershot, L. M., Harding, H. P., & Ron, D. (2000). Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nature Cell Biology, 2, 326–332.

    Article  CAS  PubMed  Google Scholar 

  • Boorstein, W. R., Ziegelhoffer, T., & Craig, E. A. (1994). Molecular evolution of the HSP70 multigene family. Journal of Molecular Evolution, 38, 1–17.

    Article  CAS  PubMed  Google Scholar 

  • Broos, K., Feys, H. B., De Meyer, S. F., Vanhoorelbeke, K., & Deckmyn, H. (2011). Platelets at work in primary hemostasis. Blood Reviews, 25, 155–167.

    Article  CAS  PubMed  Google Scholar 

  • Burkhart, J. M., Vaudel, M., Gambaryan, S., Radau, S., Walter, U., Martens, L., Geiger, J., Sickmann, A., & Zahedi, R. P. (2012). The first comprehensive and quantitative analysis of human platelet protein composition allows the comparative analysis of structural and functional pathways. Blood, 120, e73–e82.

    Article  CAS  PubMed  Google Scholar 

  • Chan, Y. C., Greenwood, D. R., Yang, Y., Leung, E., & Krissansen, G. W. (2015). Leukocyte integrin α4β7 associates with heat shock protein 70. Molecular and Cellular Biochemistry, 409(1–2), 263–269.

    Article  CAS  PubMed  Google Scholar 

  • Chen, T., & Cao, X. (2010). Stress for maintaining memory: HSP70 as a mobile messenger for innate and adaptive immunity. European Journal of Immunology, 40, 1541–1544.

    Article  CAS  PubMed  Google Scholar 

  • Chen, Z., Xu, L., Su, T., Ke, Z., Peng, Z., Zhang, N., Peng, S., Zhang, Q., Liu, G., Wei, G., Guo, Y., He, M., & Kuang, M. (2017). Autocrine STIP1 signaling promotes tumor growth and is associated with disease outcome in hepatocellular carcinoma. Biochemical and Biophysical Research Communications, 493(1), 365–372.

    Article  CAS  PubMed  Google Scholar 

  • Cho, J., Kennedy, D. R., Lin, L., Huang, M., Merrill-Skoloff, G., Furie, B. C., & Furie, B. (2012). Protein disulfide isomerase capture during thrombus formation in vivo depends on the presence of beta3 integrins. Blood, 120, 647–655.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clerico, E. M., Tilitsky, J. M., Meng, W., & Gierasch, L. M. (2015). How Hsp70 molecular machines interact with their substrates to mediate diverse physiological functions. Journal of Molecular Biology, 427, 1575–1588.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Colvin, T. A., Gabai, V. L., Gong, J., Calderwood, S. K., Li, H., Gummuluru, S., Matchuk, O. N., Smirnova, S. G., Orlova, N. V., Zamulaeva, I. A., Garcia-Marcos, M., Li, X., Young, Z. T., Rauch, J. N., Gestwicki, J. E., Takayama, S., & Sherman, M. Y. (2014). Hsp70-Bag3 interactions regulate cancer-related signaling networks. Cancer Research, 74, 4731–4740.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crescente, M., Pluthero, F. G., Li, L., Lo, R. W., Walsh, T. G., Schenk, M. P., Holbrook, L. M., Louriero, S., Ali, M. S., Vaiyapuri, S., Falet, H., Jones, I. M., Poole, A. W., Kahr, W. H., & Gibbins, J. M. (2016). Intracellular trafficking, localization, and mobilization of platelet-borne thiol isomerases. Arteriosclerosis, Thrombosis, and Vascular Biology, 36, 1164–1173.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Delom, F., Mallet, B., Carayon, P., & Lejeune, P. J. (2001). Role of extracellular molecular chaperones in the folding of oxidized proteins. Refolding of colloidal thyroglobulin by protein disulfide isomerase and immunoglobulin heavy chain-binding protein. The Journal of Biological Chemistry, 276, 21337–21342.

    Article  CAS  PubMed  Google Scholar 

  • Duerschmied, D., & Bode, C. (2016). Hsp70 preventing thrombosis: Benefit without burden? Cardiovascular Research, 110, 291–292.

    Article  CAS  PubMed  Google Scholar 

  • Durrant, T. N., Hutchinson, J. L., Heesom, K. J., Anderson, K. E., Stephens, L. R., Hawkins, P. T., Marshall, A. J., Moore, S. F., & Hers, I. (2017). In-depth PtdIns(3,4,5)P3 signalosome analysis identifies DAPP1 as a negative regulator of GPVI-driven platelet function. Blood Advances, 1, 918–932.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Furie, B., & Flaumenhaft, R. (2014). Thiol isomerases in thrombus formation. Circulation Research, 114, 1162–1173.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Galovic, R., Flegar-Mestric, Z., Vidjak, V., Matokanovic, M., & Barisic, K. (2016). Heat shock protein 70 and antibodies to heat shock protein 60 are associated with cerebrovascular atherosclerosis. Clinical Biochemistry, 49, 66–69.

    Article  CAS  PubMed  Google Scholar 

  • Gerthoffer, W. T., & Gunst, S. J. (2001). Invited review: Focal adhesion and small heat shock proteins in the regulation of actin remodeling and contractility in smooth muscle. Journal of Applied Physiology (1985), 91, 963–972.

    Article  CAS  Google Scholar 

  • Gibbins, J. M. (2013). Platelets using proteins creatively. Blood, 122, 3553–3554.

    Article  CAS  PubMed  Google Scholar 

  • Golebiewska, E. M., & Poole, A. W. (2015). Platelet secretion: From haemostasis to wound healing and beyond. Blood Reviews, 29, 153–162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gros, A., Ollivier, V., & Ho-Tin-Noe, B. (2014). Platelets in inflammation: Regulation of leukocyte activities and vascular repair. Frontiers in Immunology, 5, 678.

    PubMed  Google Scholar 

  • Gutierrez, T., & Simmen, T. (2014). Endoplasmic reticulum chaperones and oxidoreductases: Critical regulators of tumor cell survival and immunorecognition. Frontiers in Oncology, 4, 291.

    PubMed  PubMed Central  Google Scholar 

  • Hansen, G. A., Ludvigsen, M., Jacobsen, C., Cangemi, C., Rasmussen, L. M., Vorum, H., & Honore, B. (2015). Fibulin-1C, C1 esterase inhibitor and glucose regulated protein 75 interact with the CREC proteins, calumenin and Reticulocalbin. PLoS One, 10, e0132283.

    Article  PubMed  CAS  Google Scholar 

  • Hartl, F. U., Bracher, A., & Hayer-Hartl, M. (2011). Molecular chaperones in protein folding and proteostasis. Nature, 475, 324–332.

    Article  CAS  PubMed  Google Scholar 

  • Hilf, N., Singh-Jasuja, H., Schwarzmaier, P., Gouttefangeas, C., Rammensee, H. G., & Schild, H. (2002). Human platelets express heat shock protein receptors and regulate dendritic cell maturation. Blood, 99, 3676–3682.

    Article  CAS  PubMed  Google Scholar 

  • Hughes, C. E., Auger, J. M., McGlade, J., Eble, J. A., Pearce, A. C., & Watson, S. P. (2008). Differential roles for the adapters gads and LAT in platelet activation by GPVI and CLEC-2. Journal of Thrombosis and Haemostasis, 6, 2152–2159.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hutter, J. J., Mestril, R., Tam, E. K., Sievers, R. E., Dillmann, W. H., & Wolfe, C. L. (1996). Overexpression of heat shock protein 72 in transgenic mice decreases infarct size in vivo. Circulation, 94, 1408–1411.

    Article  CAS  PubMed  Google Scholar 

  • Inoue, N., & Sawamura, T. (2007). Lectin-like oxidized LDL receptor-1 as extracellular chaperone receptor: Its versatile functions and human diseases. Methods, 43, 218–222.

    Article  CAS  PubMed  Google Scholar 

  • Inwald, D. P., McDowall, A., Peters, M. J., Callard, R. E., & Klein, N. J. (2003). CD40 is constitutively expressed on platelets and provides a novel mechanism for platelet activation. Circulation Research, 92, 1041–1048.

    Article  CAS  PubMed  Google Scholar 

  • Jang, J., Kim, M. R., Kim, T. K., Lee, W. R., Kim, J. H., Heo, K., & Lee, S. (2017). CLEC14a-HSP70-1A interaction regulates HSP70-1A-induced angiogenesis. Scientific Reports, 7(10666), 10666.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kabbage, M., & Dickman, M. B. (2008). The BAG proteins: A ubiquitous family of chaperone regulators. Cellular and Molecular Life Sciences, 65, 1390–1402.

    Article  CAS  PubMed  Google Scholar 

  • Kageyama, Y., Doi, T., Akamatsu, S., Kuroyanagi, G., Kondo, A., Mizutani, J., Otsuka, T., Tokuda, H., Kozawa, O., & Ogura, S. (2013). Rac regulates collagen-induced HSP27 phosphorylation via p44/p42 MAP kinase in human platelets. International Journal of Molecular Medicine, 32, 813–818.

    Article  CAS  PubMed  Google Scholar 

  • Kaiser, W. J., Holbrook, L. M., Tucker, K. L., Stanley, R. G., & Gibbins, J. M. (2009). A functional proteomic method for the enrichment of peripheral membrane proteins reveals the collagen binding protein Hsp47 is exposed on the surface of activated human platelets. Journal of Proteome Research, 8, 2903–2914.

    Article  CAS  PubMed  Google Scholar 

  • Kampinga, H. H., & Craig, E. A. (2010). The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nature Reviews. Molecular Cell Biology, 11, 579–592.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kato, H., Takai, S., Matsushima-Nishiwaki, R., Adachi, S., Minamitani, C., Otsuka, T., Tokuda, H., Akamatsu, S., Doi, T., Ogura, S., & Kozawa, O. (2008). HSP27 phosphorylation is correlated with ADP-induced platelet granule secretion. Archives of Biochemistry and Biophysics, 475, 80–86.

    Article  CAS  PubMed  Google Scholar 

  • Kim, T. K., Na, H. J., Lee, W. R., Jeoung, M. H., & Lee, S. (2016). Heat shock protein 70-1A is a novel angiogenic regulator. Biochemical and Biophysical Research Communications, 469, 222–228.

    Article  CAS  PubMed  Google Scholar 

  • Krause, M., Heck, T. G., Bittencourt, A., Scomazzon, S. P., Newsholme, P., Curi, R., Homem de Bittencourt, P. I., & Jr. (2015). The chaperone balance hypothesis: The importance of the extracellular to intracellular HSP70 ratio to inflammation-driven type 2 diabetes, the effect of exercise, and the implications for clinical management. Mediators of Inflammation, 2015, 249205.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Krepuska, M., Szeberin, Z., Sotonyi, P., Sarkadi, H., Fehervari, M., Apor, A., Rimely, E., Prohaszka, Z., & Acsady, G. (2011). Serum level of soluble Hsp70 is associated with vascular calcification. Cell Stress & Chaperones, 16, 257–265.

    Article  CAS  Google Scholar 

  • Kruse, D. E., Mackanos, M. A., O’Connell-Rodwell, C. E., Contag, C. H., & Ferrara, K. W. (2008). Short-duration-focused ultrasound stimulation of Hsp70 expression in vivo. Physics in Medicine and Biology, 53, 3641–3660.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lalo, U., Jones, S., Roberts, J. A., Mahaut-Smith, M. P., & Evans, R. J. (2012). Heat shock protein 90 inhibitors reduce trafficking of ATP-gated P2X1 receptors and human platelet responsiveness. The Journal of Biological Chemistry, 287, 32747–32754.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lancaster, G. I., & Febbraio, M. A. (2005). Exosome-dependent trafficking of HSP70: A novel secretory pathway for cellular stress proteins. The Journal of Biological Chemistry, 280, 23349–23355.

    Article  CAS  PubMed  Google Scholar 

  • Ma, C., Yao, Y., Yue, Q. X., Zhou, X. W., Yang, P. Y., Wu, W. Y., Guan, S. H., Jiang, B. H., Yang, M., Liu, X., & Guo, D. A. (2011). Differential proteomic analysis of platelets suggested possible signal cascades network in platelets treated with salvianolic acid B. PLoS One, 6, e14692.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mambula, S. S., Stevenson, M. A., Ogawa, K., & Calderwood, S. K. (2007). Mechanisms for Hsp70 secretion: Crossing membranes without a leader. Methods, 43, 168–175.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Massey, A. J., Williamson, D. S., Browne, H., Murray, J. B., Dokurno, P., Shaw, T., Macias, A. T., Daniels, Z., Geoffroy, S., Dopson, M., Lavan, P., Matassova, N., Francis, G. L., Graham, C. J., Parsons, R., Wang, Y., Padfield, A., Comer, M., Drysdale, M. J., & Wood, M. (2010). A novel, small molecule inhibitor of Hsc70/Hsp70 potentiates Hsp90 inhibitor induced apoptosis in HCT116 colon carcinoma cells. Cancer Chemotherapy and Pharmacology, 66, 535–545.

    Article  CAS  PubMed  Google Scholar 

  • Mateos-Caceres, P. J., Macaya, C., Azcona, L., Modrego, J., Mahillo, E., Bernardo, E., Fernandez-Ortiz, A., & Lopez-Farre, A. J. (2010). Different expression of proteins in platelets from aspirin-resistant and aspirin-sensitive patients. Thrombosis and Haemostasis, 103, 160–170.

    Article  CAS  PubMed  Google Scholar 

  • Mayer, M. P., & Bukau, B. (2005). Hsp70 chaperones: Cellular functions and molecular mechanism. Cellular and Molecular Life Sciences, 62, 670–684.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Molins, B., Pena, E., Padro, T., Casani, L., Mendieta, C., & Badimon, L. (2010). Glucose-regulated protein 78 and platelet deposition: Effect of rosuvastatin. Arteriosclerosis, Thrombosis, and Vascular Biology, 30, 1246–1252.

    Article  CAS  PubMed  Google Scholar 

  • Molvarec, A., Tamasi, L., Losonczy, G., Madach, K., Prohaszka, Z., & Rigo, J.,. J. (2010). Circulating heat shock protein 70 (HSPA1A) in normal and pathological pregnancies. Cell Stress & Chaperones, 15, 237–247.

    Article  CAS  Google Scholar 

  • Nollen, E. A., & Morimoto, R. I. (2002). Chaperoning signaling pathways: Molecular chaperones as stress-sensing ‘heat shock’ proteins. Journal of Cell Science, 115, 2809–2816.

    CAS  PubMed  Google Scholar 

  • Pasquet, J. M., Gross, B., Quek, L., Asazuma, N., Zhang, W., Sommers, C. L., Schweighoffer, E., Tybulewicz, V., Judd, B., Lee, J. R., Koretzky, G., Love, P. E., Samelson, L. E., & Watson, S. P. (1999). LAT is required for tyrosine phosphorylation of phospholipase cgamma2 and platelet activation by the collagen receptor GPVI. Molecular and Cellular Biology, 19, 8326–8334.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Passam, F. H., Lin, L., Gopal, S., Stopa, J. D., Bellido-Martin, L., Huang, M., Furie, B. C., & Furie, B. (2015). Both platelet- and endothelial cell-derived ERp5 support thrombus formation in a laser-induced mouse model of thrombosis. Blood, 125, 2276–2285.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patury, S., Miyata, Y., & Gestwicki, J. E. (2009). Pharmacological targeting of the Hsp70 chaperone. Current Topics in Medicinal Chemistry, 9, 1337–1351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pichon, S., Bryckaert, M., & Berrou, E. (2004). Control of actin dynamics by p38 MAP kinase - Hsp27 distribution in the lamellipodium of smooth muscle cells. Journal of Cell Science, 117, 2569–2577.

    Article  CAS  PubMed  Google Scholar 

  • Pockley, A. G., Calderwood, S. K., & Multhoff, G. (2009). The atheroprotective properties of Hsp70: A role for Hsp70-endothelial interactions? Cell Stress & Chaperones, 14, 545–553.

    Article  CAS  Google Scholar 

  • Polanowska-Grabowska, R., Simon, C. G., Jr., Falchetto, R., Shabanowitz, J., Hunt, D. F., & Gear, A. R. (1997). Platelet adhesion to collagen under flow causes dissociation of a phosphoprotein complex of heat-shock proteins and protein phosphatase 1. Blood, 90, 1516–1526.

    CAS  PubMed  Google Scholar 

  • Pratt, W. B., & Toft, D. O. (2003). Regulation of signaling protein function and trafficking by the hsp90/hsp70-based chaperone machinery. Experimental Biology and Medicine (Maywood), 228, 111–133.

    Article  CAS  Google Scholar 

  • Rigg, R. A., Healy, L. D., Nowak, M. S., Mallet, J., Thierheimer, M. L., Pang, J., McCarty, O. J., & Aslan, J. E. (2016). Heat shock protein 70 regulates platelet integrin activation, granule secretion and aggregation. American Journal of Physiology. Cell Physiology, 310, C568–C575.

    Article  PubMed  PubMed Central  Google Scholar 

  • Rodrigues-Krause, J., Krause, M., O'Hagan, C., De Vito, G., Boreham, C., Murphy, C., Newsholme, P., & Colleran, G. (2012). Divergence of intracellular and extracellular HSP72 in type 2 diabetes: Does fat matter? Cell Stress & Chaperones, 17, 293–302.

    Article  Google Scholar 

  • Rondina, M. T., Weyrich, A. S., & Zimmerman, G. A. (2013). Platelets as cellular effectors of inflammation in vascular diseases. Circulation Research, 112, 1506–1519.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rousaki, A., Miyata, Y., Jinwal, U. K., Dickey, C. A., Gestwicki, J. E., & Zuiderweg, E. R. (2011). Allosteric drugs: The interaction of antitumor compound MKT-077 with human Hsp70 chaperones. Journal of Molecular Biology, 411, 614–632.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roy, S., Sun, A., & Redman, C. (1996). In vitro assembly of the component chains of fibrinogen requires endoplasmic reticulum factors. The Journal of Biological Chemistry, 271, 24544–24550.

    Article  CAS  PubMed  Google Scholar 

  • Saibil, H. (2013). Chaperone machines for protein folding, unfolding and disaggregation. Nature Reviews. Molecular Cell Biology, 14, 630–642.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santos, T. M., Sinzato, Y. K., Gallego, F. Q., Iessi, I. L., Volpato, G. T., Dallaqua, B., & Damasceno, D. C. (2015). Extracellular HSP70 levels in diabetic environment in rats. Cell Stress & Chaperones, 20, 595–603.

    Article  CAS  Google Scholar 

  • Schaletzki, Y., Kromrey, M. L., Broderdorf, S., Hammer, E., Grube, M., Hagen, P., Sucic, S., Freissmuth, M., Volker, U., Greinacher, A., Rauch, B. H., Kroemer, H. K., & Jedlitschky, G. (2017). Several adaptor proteins promote intracellular localisation of the transporter MRP4/ABCC4 in platelets and haematopoietic cells. Thrombosis and Haemostasis, 117, 105–115.

    Article  PubMed  Google Scholar 

  • Schlecht, R., Scholz, S. R., Dahmen, H., Wegener, A., Sirrenberg, C., Musil, D., Bomke, J., Eggenweiler, H. M., Mayer, M. P., & Bukau, B. (2013). Functional analysis of Hsp70 inhibitors. PLoS One, 8, e78443.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schulman, S., Bendapudi, P., Sharda, A., Chen, V., Bellido-Martin, L., Jasuja, R., Furie, B. C., Flaumenhaft, R., & Furie, B. (2016). Extracellular thiol isomerases and their role in thrombus formation. Antioxidants & Redox Signaling, 24, 1–15.

    Article  CAS  Google Scholar 

  • Shiraki, R., Inoue, N., Kawasaki, S., Takei, A., Kadotani, M., Ohnishi, Y., Ejiri, J., Kobayashi, S., Hirata, K., Kawashima, S., & Yokoyama, M. (2004). Expression of toll-like receptors on human platelets. Thrombosis Research, 113, 379–385.

    Article  CAS  PubMed  Google Scholar 

  • Smyth, S. S., McEver, R. P., Weyrich, A. S., Morrell, C. N., Hoffman, M. R., Arepally, G. M., French, P. A., Dauerman, H. L., & Becker, R. C. (2009). Platelet functions beyond hemostasis. Journal of Thrombosis and Haemostasis, 7, 1759–1766.

    Article  CAS  PubMed  Google Scholar 

  • Somensi, N., Brum, P. O., de Miranda Ramos, V., Gasparotto, J., Zanotto-Filho, A., Rostirolla, D. C., da Silva Morrone, M., Moreira, J. C. F., & Pens Gelain, D. (2017). Extracellular HSP70 activates ERK1/2, NF-kB and pro-inflammatory gene transcription through binding with RAGE in A549 human lung cancer cells. Cellular Physiology and Biochemistry, 42, 2507–2522.

    Article  CAS  PubMed  Google Scholar 

  • Staron, M., Wu, S., Hong, F., Stojanovic, A., Du, X., Bona, R., Liu, B., & Li, Z. (2011). Heat-shock protein gp96/grp94 is an essential chaperone for the platelet glycoprotein Ib-IX-V complex. Blood, 117, 7136–7144.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sturner, E., & Behl, C. (2017). The role of the multifunctional BAG3 protein in cellular protein quality control and in disease. Frontiers in Molecular Neuroscience, 10, 177.

    Article  PubMed  PubMed Central  Google Scholar 

  • Suttitanamongkol, S., Polanowska-Grabowska, R., & Gear, A. R. (2002). Heat-shock protein 90 complexes in resting and thrombin-activated platelets. Biochemical and Biophysical Research Communications, 297, 129–133.

    Article  CAS  PubMed  Google Scholar 

  • Suzuki, H., Kosuge, Y., Kobayashi, K., Kurosaki, Y., Ishii, N., Aoyama, N., Ishihara, K., & Ichikawa, T. (2017). Heat-shock protein 72 promotes platelet aggregation induced by various platelet activators in rats. Biomedical Research, 38, 175–182.

    Article  CAS  PubMed  Google Scholar 

  • Swiatkowska, M., Padula, G., Michalec, L., Stasiak, M., Skurzynski, S., & Cierniewski, C. S. (2010). Ero1alpha is expressed on blood platelets in association with protein-disulfide isomerase and contributes to redox-controlled remodeling of alphaIIbbeta3. The Journal of Biological Chemistry, 285, 29874–29883.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Theriault, J. R., Mambula, S. S., Sawamura, T., Stevenson, M. A., & Calderwood, S. K. (2005). Extracellular HSP70 binding to surface receptors present on antigen presenting cells and endothelial/epithelial cells. FEBS Letters, 579, 1951–1960.

    Article  CAS  PubMed  Google Scholar 

  • Tokuda, H., Kuroyanagi, G., Tsujimoto, M., Enomoto, Y., Matsushima-Nishiwaki, R., Onuma, T., Kojima, A., Doi, T., Tanabe, K., Akamatsu, S., Iida, H., Ogura, S., Otsuka, T., Iwama, T., Tanikawa, T., Ishikawa, K., Kojima, K., & Kozawa, O. (2015). Release of phosphorylated HSP27 (HSPB1) from platelets is accompanied with the acceleration of aggregation in diabetic patients. PLoS One, 10, e0128977.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Traister, A., Walsh, M., Aafaqi, S., Lu, M., Dai, X., Henkleman, M. R., Momen, A., Zhou, Y. Q., Husain, M., Arab, S., Piran, S., Hannigan, G., & Coles, J. G. (2013). Mutation in integrin-linked kinase (ILK(R211A)) and heat-shock protein 70 comprise a broadly cardioprotective complex. PLoS One, 8, e77331.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tran, H., Tanaka, A., Litvinovich, S. V., Medved, L. V., Haudenschild, C. C., & Argraves, W. S. (1995). The interaction of fibulin-1 with fibrinogen. A potential role in hemostasis and thrombosis. The Journal of Biological Chemistry, 270, 19458–19464.

    Article  CAS  PubMed  Google Scholar 

  • Tucker, K. L., Sage, T., Stevens, J. M., Jordan, P. A., Jones, S., Barrett, N. E., St-Arnaud, R., Frampton, J., Dedhar, S., & Gibbins, J. M. (2008). A dual role for integrin-linked kinase in platelets: Regulating integrin function and alpha-granule secretion. Blood, 112, 4523–4531.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vega, V. L., Rodriguez-Silva, M., Frey, T., Gehrmann, M., Diaz, J. C., Steinem, C., Multhoff, G., Arispe, N., & De Maio, A. (2008). Hsp70 translocates into the plasma membrane after stress and is released into the extracellular environment in a membrane-associated form that activates macrophages. Journal of Immunology, 180, 4299–4307.

    Article  CAS  Google Scholar 

  • Verba, K. A., & Agard, D. A. (2017). How Hsp90 and Cdc37 lubricate kinase molecular switches. Trends in Biochemical Sciences, 42(10), 799–811.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vinokurov, M., Ostrov, V., Yurinskaya, M., Garbuz, D., Murashev, A., Antonova, O., & Evgen'ev, M. (2012). Recombinant human Hsp70 protects against lipoteichoic acid-induced inflammation manifestations at the cellular and organismal levels. Cell Stress & Chaperones, 17, 89–101.

    Article  CAS  Google Scholar 

  • Wadhwa, R., Sugihara, T., Yoshida, A., Nomura, H., Reddel, R. R., Simpson, R., Maruta, H., & Kaul, S. C. (2000). Selective toxicity of MKT-077 to cancer cells is mediated by its binding to the hsp70 family protein mot-2 and reactivation of p53 function. Cancer Research, 60, 6818–6821.

    CAS  PubMed  Google Scholar 

  • Wang, L., Wu, Y., Zhou, J., Ahmad, S. S., Mutus, B., Garbi, N., Hammerling, G., Liu, J., & Essex, D. W. (2013). Platelet-derived ERp57 mediates platelet incorporation into a growing thrombus by regulation of the alphaIIbbeta3 integrin. Blood, 122, 3642–3650.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, Y. L., Shen, H. H., Cheng, P. Y., Chu, Y. J., Hwang, H. R., Lam, K. K., & Lee, Y. M. (2016). 17-DMAG, an HSP90 inhibitor, ameliorates multiple organ dysfunction syndrome via induction of HSP70 in Endotoxemic rats. PLoS One, 11, e0155583.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Watson, S. P. (2009). Platelet activation by extracellular matrix proteins in haemostasis and thrombosis. Current Pharmaceutical Design, 15, 1358–1372.

    Article  CAS  PubMed  Google Scholar 

  • Watson, S. P., Auger, J. M., McCarty, O. J., & Pearce, A. C. (2005). GPVI and integrin alphaIIb beta3 signaling in platelets. Journal of Thrombosis and Haemostasis, 3, 1752–1762.

    Article  CAS  PubMed  Google Scholar 

  • Williamson, D. S., Borgognoni, J., Clay, A., Daniels, Z., Dokurno, P., Drysdale, M. J., Foloppe, N., Francis, G. L., Graham, C. J., Howes, R., Macias, A. T., Murray, J. B., Parsons, R., Shaw, T., Surgenor, A. E., Terry, L., Wang, Y., Wood, M., & Massey, A. J. (2009). Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design. Journal of Medicinal Chemistry, 52, 1510–1513.

    Article  CAS  PubMed  Google Scholar 

  • Wonerow, P., Obergfell, A., Wilde, J. I., Bobe, R., Asazuma, N., Brdicka, T., Leo, A., Schraven, B., Horejsi, V., Shattil, S. J., & Watson, S. P. (2002). Differential role of glycolipid-enriched membrane domains in glycoprotein VI- and integrin-mediated phospholipase Cgamma2 regulation in platelets. The Biochemical Journal, 364, 755–765.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wyatt, A. R., Yerbury, J. J., Ecroyd, H., & Wilson, M. R. (2013). Extracellular chaperones and proteostasis. Annual Review of Biochemistry, 82, 295–322.

    Article  CAS  PubMed  Google Scholar 

  • Zeiler, M., Moser, M., & Mann, M. (2014). Copy number analysis of the murine platelet proteome spanning the complete abundance range. Molecular & Cellular Proteomics, 13, 3435–3445.

    Article  CAS  Google Scholar 

  • Zhang, G., Liu, Z., Ding, H., Zhou, Y., Doan, H. A., Sin, K. W. T., Zhu, Z. J., Flores, R., Wen, Y., Gong, X., Liu, Q., & Li, Y. P. (2017). Tumor induces muscle wasting in mice through releasing extracellular Hsp70 and Hsp90. Nature Communications, 8, 589.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhu, Y., O'Neill, S., Saklatvala, J., Tassi, L., & Mendelsohn, M. E. (1994). Phosphorylated HSP27 associates with the activation-dependent cytoskeleton in human platelets. Blood, 84, 3715–3723.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank the Knight Cardiovascular Institute, the National Institutes of Health (R01HL101972 and R01GM116184 to O.J.T.M.), and the American Heart Association (17SDG33350075 to J.E.A. and 13EIA12630000 to O.J.T.M.) for support.

Disclosures

The authors have no conflicts of interest to declare.

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA

    Rachel A. Rigg & Owen J. T. McCarty

  2. Department of Cell, Developmental & Cancer Biology, Oregon Health & Science University, Portland, OR, USA

    Owen J. T. McCarty

  3. Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR, USA

    Owen J. T. McCarty

  4. Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, OR, USA

    Joseph E. Aslan

  5. Knight Cardiovascular Institute, School of Medicine, Oregon Health & Science University, Portland, OR, USA

    Joseph E. Aslan

Authors
  1. Rachel A. Rigg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Owen J. T. McCarty
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joseph E. Aslan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joseph E. Aslan .

Editor information

Editors and Affiliations

  1. Department of Medicine and Precision Therapeutics Proteogenomics Diagnostic Center, Eleanor N. Dana Cancer Center, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA

    Alexzander A A Asea

  2. Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Punit Kaur

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Rigg, R.A., McCarty, O.J.T., Aslan, J.E. (2018). Heat Shock Protein 70 (Hsp70) in the Regulation of Platelet Function. In: Asea, A., Kaur, P. (eds) Regulation of Heat Shock Protein Responses. Heat Shock Proteins, vol 13. Springer, Cham. https://doi.org/10.1007/978-3-319-74715-6_14

Download citation

Publish with us

Policies and ethics

Search

Navigation