The contribution of oxidative stress to platelet senescence during storage
Li Wang
Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts
Department of Dermatology, Harvard Medical School, Boston, Massachusetts
Search for more papers by this authorRufeng Xie
Blood Engineering Laboratory, Shanghai Blood Center, Shanghai, China
Search for more papers by this authorZhijia Fan
Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
Search for more papers by this authorJie Yang
Blood Engineering Laboratory, Shanghai Blood Center, Shanghai, China
Search for more papers by this authorWei Liang
Department of Laboratory Medicine, The Second People's Hospital of Lianyungang City, Jiangsu Province, China
Search for more papers by this authorQiang Wu
Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
Department of Clinical Laboratory Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China
Search for more papers by this authorMei X. Wu
Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts
Department of Dermatology, Harvard Medical School, Boston, Massachusetts
Search for more papers by this authorCorresponding Author
Zhicheng Wang
Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts
Department of Dermatology, Harvard Medical School, Boston, Massachusetts
Address reprint requests to: Zhicheng Wang and Yuan Lu, Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China; e-mail: [email protected] (ZCW); [email protected] (YL)Search for more papers by this authorCorresponding Author
Yuan Lu
Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
Address reprint requests to: Zhicheng Wang and Yuan Lu, Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China; e-mail: [email protected] (ZCW); [email protected] (YL)Search for more papers by this authorLi Wang
Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts
Department of Dermatology, Harvard Medical School, Boston, Massachusetts
Search for more papers by this authorRufeng Xie
Blood Engineering Laboratory, Shanghai Blood Center, Shanghai, China
Search for more papers by this authorZhijia Fan
Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
Search for more papers by this authorJie Yang
Blood Engineering Laboratory, Shanghai Blood Center, Shanghai, China
Search for more papers by this authorWei Liang
Department of Laboratory Medicine, The Second People's Hospital of Lianyungang City, Jiangsu Province, China
Search for more papers by this authorQiang Wu
Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
Department of Clinical Laboratory Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China
Search for more papers by this authorMei X. Wu
Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts
Department of Dermatology, Harvard Medical School, Boston, Massachusetts
Search for more papers by this authorCorresponding Author
Zhicheng Wang
Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts
Department of Dermatology, Harvard Medical School, Boston, Massachusetts
Address reprint requests to: Zhicheng Wang and Yuan Lu, Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China; e-mail: [email protected] (ZCW); [email protected] (YL)Search for more papers by this authorCorresponding Author
Yuan Lu
Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
Address reprint requests to: Zhicheng Wang and Yuan Lu, Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China; e-mail: [email protected] (ZCW); [email protected] (YL)Search for more papers by this authorAbstract
BACKGROUND
Platelets for transfusion become senescent and dysfunctional during storage, resulting in a markedly short shelf life (5 days). We hypothesized that oxidative stress might account for this decline.
STUDY DESIGN AND METHODS
Human platelets were treated with or without antioxidants before storage, and samples were collected and analyzed at different time points. Platelet senescence was determined by senescence-associated β-galactosidase assay, and senescence-related platelet qualities were also analyzed.
RESULTS
Sign of senescence became evident after Day 3 and continued to increase over time. We also found that chemical induction of platelet activation did not affect senescence level, whereas apoptosis inducers showed a stimulative effect on platelet senescence. Moreover, this effect was not prevented by a pan-caspase inhibitor. Meanwhile, cellular and mitochondrial reactive oxygen species were found elevated during storage, and treatments with antioxidants successfully prevented this increase and also mitigated senescence levels of stored platelets. Finally, resveratrol, a natural antioxidant, was utilized as a novel storage additive to safely extend platelet shelf time. We showed that the addition of resveratrol efficiently postponed platelet senescence and ameliorated platelet storage lesion.
CONCLUSIONS
Platelets during storage became senescent and dysfunctional over time, and we found that oxidative stress might account for this decline. The addition of antioxidants effectively postponed senescence and ameliorated platelet storage lesion, which might provide a valuable reference to future platelet storage methodologies.
CONFLICT OF INTERESTS
The authors have disclosed no conflicts of interest.
Supporting Information
Filename | Description |
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trf15291-sup-0001-FigureS1.docxWord 2007 document , 484.3 KB | Figure S1. Resveratrol did not affect platelet metabolic levels during storage. Platelets were treated with vehicle or 50 μM of resveratrol before storage and stored for up to 7 days at the standard blood banking conditions. At the desired time points, (A) MPV, (B) platelet count, (C) pH, and (D) glucose level were measured. Mean ± standard error of the mean. n = 3 (B and D), n = 5 (C). Significance was determined by two-way analysis of variance with Dunnett's posttest. *p < 0.05, **p < 0.01, ***p < 0.001. |
trf15291-sup-0002-TableS1.xlsxExcel 2007 spreadsheet , 189.6 KB | Table S1. The TMT LC-MS/MS proteomic analysis during platelets storage |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Hayflick L. The illusion of cell immortality. Br J Cancer 2000; 83: 841-6.
- 2Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol 1956; 11: 298-300.
- 3Sena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species. Mol Cell 2012; 48: 158-67.
- 4Veatch JR, McMurray MA, Nelson ZW, et al. Mitochondrial dysfunction leads to nuclear genome instability via an iron-sulfur cluster defect. Cell 2009; 137: 1247-58.
- 5Marchi S, Giorgi C, Suski JM, et al. Mitochondria-ROS crosstalk in the control of cell death and aging. J Signal Transduct 2012; 2012: 329635.
- 6Dumont LJ, Gulliksson H, van der Meer PF, et al. Interruption of agitation of platelet concentrates: a multicenter in vitro study by the BEST Collaborative on the effects of shipping platelets. Transfusion 2007; 47: 1666-73.
- 7Rumjantseva V, Hoffmeister KM. Novel and unexpected clearance mechanisms for cold platelets. Transfus Apher Sci 2010; 42: 63-70.
- 8Holme S, Heaton A. In vitro platelet ageing at 22 degrees C is reduced compared to in vivo ageing at 37 degrees C. Br J Haematol 1995; 91: 212-8.
- 9Capocelli KE, Dumont LJ. Novel platelet storage conditions: additive solutions, gas, and cold. Curr Opin Hematol 2014; 21: 491-6.
- 10Shrivastava M. The platelet storage lesion. Transfus Apher Sci 2009; 41: 105-13.
- 11Thon JN, Devine DV. Translation of glycoprotein IIIa in stored blood platelets. Transfusion 2007; 47: 2260-70.
- 12Rosenfeld BA, Herfel B, Faraday N, et al. Effects of storage time on quantitative and qualitative platelet function after transfusion. Anesthesiology 1995; 83: 1167-72.
- 13Seghatchian J, Krailadsiri P. Platelet storage lesion and apoptosis: are they related? Transfus Apher Sci 2001; 24: 103-5.
- 14Leytin V, Freedman J. Platelet apoptosis in stored platelet concentrates and other models. Transfus Apher Sci 2003; 28: 285-95.
- 15Brown SB, Clarke MC, Magowan L, et al. Constitutive death of platelets leading to scavenger receptor-mediated phagocytosis. A caspase-independent cell clearance program. J Biol Chem 2000; 275: 5987-96.
- 16Wang Z, Cai F, Chen X, et al. The role of mitochondria-derived reactive oxygen species in hyperthermia-induced platelet apoptosis. PLoS One 2013; 8: e75044.
- 17Plenchette S, Moutet M, Benguella M, et al. Early increase in DcR2 expression and late activation of caspases in the platelet storage lesion. Leukemia 2001; 15: 1572-81.
- 18Xie R, Yang Y, Zhu Y, et al. Microparticles in red cell concentrates prime polymorphonuclear neutrophils and cause acute lung injury in a two-event mouse model. Int Immunopharmacol 2018; 55: 98-104.
- 19Dimri GP, Lee X, Basile G, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A 1995; 92: 9363-7.
- 20Kumar S, Vikram A, Kim YR, et al. P66Shc mediates increased platelet activation and aggregation in hypercholesterolemia. Biochem Biophys Res Commun 2014; 449: 496-501.
- 21De Cuyper IM, Meinders M, van de Vijver E, et al. A novel flow cytometry-based platelet aggregation assay. Blood 2013; 121: e70-80.
- 22Lee BY, Han JA, Im JS, et al. Senescence-associated beta-galactosidase is lysosomal beta-galactosidase. Aging Cell 2006; 5: 187-95.
- 23Seghatchian J. A new platelet storage lesion index based on paired samples, without and with EDTA and cell counting: comparison of three types of leukoreduced preparations. Transfus Apher Sci 2006; 35: 283-92.
- 24Perales Villarroel JP, Figueredo R, Guan Y, et al. Increased platelet storage time is associated with mitochondrial dysfunction and impaired platelet function. J Surg Res 2013; 184: 422-9.
- 25Black A, Pienimaeki-Roemer A, Kenyon O, et al. Platelet-derived extracellular vesicles in plateletpheresis concentrates as a quality control approach. Transfusion 2015; 55: 2184-96.
- 26Vajen T, Mause SF, Koenen RR. Microvesicles from platelets: novel drivers of vascular inflammation. Thromb Haemost 2015; 114: 228-36.
- 27Bertino AM, Qi XQ, Li J, et al. Apoptotic markers are increased in platelets stored at 37 degrees C. Transfusion 2003; 43: 857-66.
- 28Mutlu A, Gyulkhandanyan AV, Freedman J, et al. Activation of caspases-9, −3 and −8 in human platelets triggered by BH3-only mimetic ABT-737 and calcium ionophore A23187: caspase-8 is activated via bypass of the death receptors. Br J Haematol 2012; 159: 565-71.
- 29Gyulkhandanyan AV, Mutlu A, Allen DJ, et al. BH3-mimetic ABT-737 induces strong mitochondrial membrane depolarization in platelets but only weakly stimulates apoptotic morphological changes, platelet shrinkage and microparticle formation. Thromb Res 2014; 133: 73-9.
- 30Kreutz RP, Nystrom P, Kreutz Y, et al. Inhibition of platelet aggregation by prostaglandin E1 (PGE1) in diabetic patients during therapy with clopidogrel and aspirin. Platelets 2013; 24: 145-50.
- 31Wang Z, Wang J, Xie R, et al. Mitochondria-derived reactive oxygen species play an important role in Doxorubicin-induced platelet apoptosis. Int J Mol Sci 2015; 16: 11087-100.
- 32Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell 2005; 120: 483-95.
- 33Migliaccio E, Giorgio M, Mele S, et al. The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature 1999; 402: 309-13.
- 34Luzi L, Confalonieri S, Di FP, et al. Evolution of Shc functions from nematode to human. Curr Opin Genet Dev 2000; 10: 668-74.
- 35Le S, Connors TJ, Maroney AC. c-Jun N-terminal kinase specifically phosphorylates p66ShcA at serine 36 in response to ultraviolet irradiation. J Biol Chem 2001; 276: 48332-6.
- 36Lannan KL, Refaai MA, Ture SK, et al. Resveratrol preserves the function of human platelets stored for transfusion. Br J Haematol 2016; 172: 794-806.
- 37Bhat KPL, Kosmeder JW 2nd, Pezzuto JM. Biological effects of resveratrol. Antioxid Redox Signal 2001; 3: 1041-64.
- 38Poulsen MM, Vestergaard PF, Clasen BF, et al. High-dose resveratrol supplementation in obese men: an investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition. Diabetes 2013; 62: 1186-95.
- 39Liu T, Qi H, Ma L, et al. Resveratrol attenuates oxidative stress and extends life span in the annual fish Nothobranchius guentheri. Rejuvenation Res 2015; 18: 225-33.
- 40Chen W, Rezaizadehnajafi L, Wink M. Influence of resveratrol on oxidative stress resistance and life span in Caenorhabditis elegans. J Pharm Pharmacol 2013; 65: 682-8.
- 41Strong R, Miller RA, Astle CM, et al. Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice. J Gerontol A Biol Sci Med Sci 2013; 68: 6-16.
- 42Ekaney ML, Gray GG, McKillop IH, et al. Enhanced platelet function in cold stored whole blood supplemented with resveratrol or cytochrome C. J Trauma Acute Care Surg 2018; 85: S92-S97.
- 43Jagadish S, Rajeev N, NaveenKumar SK, et al. Platelet protective efficacy of 3,4,5 trisubstituted isoxazole analogue by inhibiting ROS-mediated apoptosis and platelet aggregation. Mol Cell Biochem 2016; 414: 137-51.
- 44Rakesh KS, Jagadish S, Vinayaka AC, et al. A new ibuprofen derivative inhibits platelet aggregation and ROS mediated platelet apoptosis. PLoS One 2014; 9: e107182.
- 45Fletcher NM, Jiang ZL, Diamond MP, et al. Hypoxia-generated superoxide induces the development of the adhesion phenotype. Free Radic Biol Med 2008; 45: 530-6.
- 46Juan ME, Vinardell MP, Planas JM. The daily oral administration of high doses of trans-resveratrol to rats for 28 days is not harmful. J Nutr 2002; 132: 257-60.
- 47Iranshahy M, Mohammadpoor AH, Hassanzadeh-Khayyat M, et al. Method validation for the one-month stability study of trans-resveratrol in human plasma. Jundishapur J Nat Pharm Prod 2013; 8: 65-9.
- 48Walle T, Hsieh F, DeLegge MH, et al. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos 2004; 32: 1377-82.
- 49Ekaney ML, Grable MA, Powers WF, et al. Cytochrome C and resveratrol preserve platelet function during cold storage. J Trauma Acute Care Surg 2017; 83: 271-7.
- 50Guida N, Laudati G, Anzilotti S, et al. Resveratrol via sirtuin-1 downregulates RE1-silencing transcription factor (REST) expression preventing PCB-95-induced neuronal cell death. Toxicol Appl Pharmacol 2015; 288: 387-98.
- 51Freund A, Laberge RM, Demaria M, et al. Lamin B1 loss is a senescence-associated biomarker. Mol Biol Cell 2012; 23: 2066-75.
- 52Davalos AR, Kawahara M, Malhotra GK, et al. p53-dependent release of Alarmin HMGB1 is a central mediator of senescent phenotypes. J Cell Biol 2013; 201: 613-29.
- 53Campisi J. d'Adda di Fagagna F. Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol 2007; 8: 729-40.