Ristocetin induces phosphorylated‑HSP27 (HSPB1) release from the platelets of type 2 DM patients: Anti‑platelet agent‑effect on the release

Tokuda,Haruhiko; Kuroyanagi,Gen; Onuma,Takashi; Enomoto,Yukiko; Doi,Tomoaki; Iida,Hiroki; Otsuka,Takanobu; Ogura,Shinji; Iwama,Toru; Kojima,Kumi; Kozawa,Osamu

doi:10.3892/br.2018.1058

Ristocetin induces phosphorylated‑HSP27 (HSPB1) release from the platelets of type 2 DM patients: Anti‑platelet agent‑effect on the release

Authors:
- Haruhiko Tokuda
- Gen Kuroyanagi
- Takashi Onuma
- Yukiko Enomoto
- Tomoaki Doi
- Hiroki Iida
- Takanobu Otsuka
- Shinji Ogura
- Toru Iwama
- Kumi Kojima
- Osamu Kozawa
View Affiliations

Affiliations: Department of Clinical Laboratory/Biobank of Medical Genome Center, National Center for Geriatrics and Gerontology, Obu, Aichi 474‑8511, Japan, Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan, Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan, Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan, Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu 501‑1194, Japan, Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467‑8601, Japan
Published online on: February 6, 2018 https://doi.org/10.3892/br.2018.1058
Pages: 365-372

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

It has been previously reported that HSP27 is released from platelets in type 2 diabetes mellitus (DM) patients according to phosphorylation. In the present study, we investigated the effect of ristocetin, a glycoprotein (GP)Ib/IX/V activator, on the release of HSP27 and the effect of anti‑platelet agents, such as acetylsalicylic acid (ASA), on this release. Forty-six patients with type 2 DM were recruited, and classified into two groups depending on administration of anti‑platelet agents, resulting in 31 patients without these agents (control group) and 15 patients with them (anti‑platelet group). Ristocetin potently induced the aggregation of platelets in the two groups. Ristocetin‑induced changes of the area under the curve of light transmittance and the ratio of the size of platelet aggregates in the anti‑platelet group were slightly different from those in the control group. On the other hand, the levels of phosphorylated‑HSP27 induced by ristocetin in the platelets from a patient of the anti‑platelet group taking ASA were significantly lower than those from a patient of the control group. The levels of HSP27 release from the ristocetin‑stimulated platelets were significantly correlated with the levels of phosphorylated‑HSP27 in the platelets from patients in the two groups. The levels of HSP27 release and those of platelet‑derived growth factor‑AB (PDGF‑AB) secretion stimulated by ristocetin in the anti‑platelet group were lower than those in the control group. In addition, the levels of HSP27 release and those of PDGF‑AB secretion stimulated by ADP in the anti‑platelet group were lower than those in the control group. These results strongly suggest that anti‑platelet agents inhibit the HSP27 release from platelets stimulated by ristocetin but not the aggregation in type 2 DM patients.

View Figures

View References

1	Davì G and Patrono C: Platelet activation and atherothrombosis. N Engl J Med. 357:2482–2494. 2007. View Article : Google Scholar : PubMed/NCBI
2	Furie B and Furie BC: Mechanisms of thrombus formation. N Engl J Med. 359:938–949. 2008. View Article : Google Scholar : PubMed/NCBI
3	Berndt MC, Shen Y, Dopheide SM, Gardiner EE and Andrews RK: The vascular biology of the glycoprotein Ib-IX–V complex. Thromb Haemost. 86:178–188. 2001.PubMed/NCBI
4	Garcia A, Quinton TM, Dorsam RT and Kunapuli SP: Src family kinase-mediated and Erk-mediated thromboxane A2 generation are essential for VWF/GPIb-induced fibrinogen receptor activation in human platelets. Blood. 106:3410–3414. 2005. View Article : Google Scholar : PubMed/NCBI
5	Dong JF, Berndt MC, Schade A, McIntire LV, Andrews RK and López JA: Ristocetin-dependent, but not botrocetin-dependent, binding of von Willebrand factor to the platelet glycoprotein Ib-IX–V complex correlates with shear-dependent interactions. Blood. 97:162–168. 2001. View Article : Google Scholar : PubMed/NCBI
6	Enomoto Y, Adachi S, Matsushima-Nishiwaki R, Doi T, Niwa M, Akamatsu S, Tokuda H, Yoshimura S, Iwama T and Kozawa O: Thromboxane A2 promotes soluble CD40 ligand release from platelets in atherosclerotic patients. Athelosclerosis. 209:415–421. 2010. View Article : Google Scholar
7	Zimmet P, Alberti KG and Shaw J: Global and societal implications of the diabetes epidemic. Nature. 414:782–787. 2001. View Article : Google Scholar : PubMed/NCBI
8	Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard BV, Mitch W, Smith SC Jr and Sowers JR: Diabetes and cardiovascular disease: A statement for healthcare professionals from the American Heart Association. Circulation. 100:1134–1146. 1999. View Article : Google Scholar : PubMed/NCBI
9	Matsuno H, Tokuda H, Ishisaki A, Zhou Y, Kitajima Y and Kozawa O: P2Y12 receptors play a significant role in the development of platelet microaggregation in patients with diabetes. J Clin Endocrinol Metab. 90:920–927. 2005. View Article : Google Scholar : PubMed/NCBI
10	Hanai Y, Adachi S, Yasuda I, Takai S, Matsushima-Nishiwaki R, Kato H, Enomoto Y, Akamatsu S, Sakakibara S, Ogura S, et al: Collagen-induced p38 MAP kinase activation is a biomarker of platelet hyper-aggregation in patients with diabetes mellitus. Life Sci. 85:386–394. 2009. View Article : Google Scholar : PubMed/NCBI
11	Colwell JA; American Diabetes Association, : Aspirin therapy in diabetes. Diabetes Care. 26 Suppl 1:S87–S88. 2003. View Article : Google Scholar : PubMed/NCBI
12	Hankey GJ and Eikelboom JW: Aspirin resistance. Lancet. 367:606–617. 2006. View Article : Google Scholar : PubMed/NCBI
13	Mymrikov EV, Seit-Nebi AS and Gusev NB: Large potentials of small heat shock proteins. Physiol Rev. 91:1123–1159. 2011. View Article : Google Scholar : PubMed/NCBI
14	Bruey JM, Ducasse C, Bonniaud P, Ravagnan L, Susin SA, Diaz-Latoud C, Gurbuxani S, Arrigo AP, Kroemer G, Solary E, et al: Hsp27 negatively regulates cell death by interacting with cytochrome c. Nat Cell Biol. 2:645–652. 2000. View Article : Google Scholar : PubMed/NCBI
15	Arrigo AP: The cellular ‘networking’ of mammalian Hsp27 and its functions in the control of protein folding, redox state and apoptosis. Adv Exp Med Biol. 594:14–26. 2007. View Article : Google Scholar : PubMed/NCBI
16	Pockley AG: Heat shock proteins, inflammation, and cardiovascular disease. Circulation. 105:1012–1017. 2002. View Article : Google Scholar : PubMed/NCBI
17	Landry J, Lambert H, Zhou M, Lavoie JN, Hickey E, Weber LA and Anderson CW: Human HSP27 is phosphorylated at serines 78 and 82 by heat shock and mitogen-activated kinases that recognize the same amino acid motif as S6 kinase II. J Biol Chem. 267:794–803. 1992.PubMed/NCBI
18	Acunzo J, Katsogiannou M and Rocchi P: Small heat shock proteins HSP27 (HspB1), αB-crystallin (HspB5) and HSP22 (HspB8) as regulators of cell death. Int J Biochem Cell Biol. 44:1622–1631. 2012. View Article : Google Scholar : PubMed/NCBI
19	Saklatvala J, Rawlinson L, Waller RJ, Sarsfield S, Lee JC, Morton LF, Barnes MJ and Farndale RW: Role for p38 mitogen-activated protein kinase in platelet aggregation caused by collagen or a thromboxane analogue. J Biol Chem. 271:6586–6589. 1996. View Article : Google Scholar : PubMed/NCBI
20	Kageyama Y, Doi T, Akamatsu S, Kuroyanagi G, Kondo A, Mizutani J, Otsuka T, Tokuda H, Kozawa O and Ogura S: Rac regulates collagen-induced HSP27 phosphorylation via p44/p42 MAP kinase in human platelets. Int J Mol Med. 32:813–818. 2013. View Article : Google Scholar : PubMed/NCBI
21	Tokuda H, Kuroyanagi G, Tsujimoto M, Enomoto Y, Matsushima-Nishiwaki R, Onuma T, Kojima A, Doi T, Tanabe K, Akamatsu S, et al: Release of phosphorylated HSP27 (HSPB1) from platelets is accompanied with the accerelation of aggregation in diabetic patients. PLoS One. 10:e01289772015. View Article : Google Scholar : PubMed/NCBI
22	Tokuda H, Kuroyanagi G, Tsujimoto M, Matsushima-Nishiwaki R, Akamatsu S, Enomoto Y, Iida H, Otsuka T, Ogura S, Iwama T, et al: Thrombin receptor-activating protein (TRAP)-activated Akt is involved in the release of phosphorylated-HSP27 (HSPB1) from platelets in DM patients. Int J Mol Sci. 17(pii): E7372016. View Article : Google Scholar : PubMed/NCBI
23	Reddy VS, Madala SK, Trinath J and Reddy GB: Extracellular small heat shock proteins: exosomal biogenesis and function. Cell Stress Chaperones. Oct 30–2017.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI
24	Kato K, Ito H, Hasegawa K, Inaguma Y, Kozawa O and Asano T: Modulation of the stress-induced synthesis of hsp27 and alpha B-crystallin by cyclic AMP in C6 rat glioma cells. J Neurochem. 66:946–950. 1996. View Article : Google Scholar : PubMed/NCBI
25	Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 227:680–685. 1970. View Article : Google Scholar : PubMed/NCBI
26	Liu J, Pestina TI, Berndt MC, Steward SA, Jackson CW and Gartner TK: The roles of ADP and TXA in botrocetin/VWF-induced aggregation of washed platelets. J Thromb Haemost. 2:2213–2222. 2004. View Article : Google Scholar : PubMed/NCBI
27	Kato H, Takai S, Matsushima-Nishiwaki R, Adachi S, Minamitani C, Otsuka T, Tokuda H, Akamatsu S, Doi T, Ogura S, et al: HSP27 phosphorylation is correlated with ADP-induced platelet granule secretion. Arch Biochem Biophys. 475:80–86. 2008. View Article : Google Scholar : PubMed/NCBI
28	Rayner K, Chen YX, McNulty M, Simard T, Zhao X, Wells DJ, de Belleroche J and O'Brien ER: Extracellular release of the atheroprotective heat shock protein 27 is mediated by estrogen and competitively inhibits acLDL binding to scavenger receptor-A. Circ Res. 103:133–141. 2008. View Article : Google Scholar : PubMed/NCBI
29	Thuringer D, Jego G, Wettstein G, Terrier O, Cronier L, Yousfi N, Hébrard S, Bouchot A, Hazoumé A, Joly AL, et al: Extracellular HSP27 mediates angiogenesis through Toll-like receptor 3. FASEB J. 27:4169–4183. 2013. View Article : Google Scholar : PubMed/NCBI
30	Salari S, Seibert T, Chen YX, Hu T, Shi C, Zhao X, Cuerrier CM, Raizman JE and O'Brien ER: Extracellular HSP27 acts as a signaling molecule to activate NF-κB in macrophages. Cell Stress Chaperones. 18:53–63. 2013. View Article : Google Scholar : PubMed/NCBI
31	Jin C, Cleveland JC, Ao L, Li J, Zeng Q, Fullerton DA and Meng X: Human myocardium releases heat shock protein 27 (HSP27) after global ischemia: The proinflammatory effect of extracellular HSP27 through toll-like receptor (TLR)-2 and TLR4. Mol Med. 20:280–289. 2014. View Article : Google Scholar : PubMed/NCBI