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Erschienen in: Indian Journal of Hematology and Blood Transfusion 4/2023

08.03.2023 | ORIGINAL ARTICLE

High Autophagy Patterns in Swelling Platelets During Apheresis Platelet Storage

verfasst von: Lu Yu, Shifang Yu, Yunlei He, Gang Deng, Qiang Li

Erschienen in: Indian Journal of Hematology and Blood Transfusion | Ausgabe 4/2023

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Abstract

Platelets undergo remarkable morphological changes during storage. Platelets change into different sizes and densities and differ in their biochemistry and functions. However, the correlation between structural heterogeneity and platelet autophagy is largely unknown. The aim of this study was to investigate the autophagy process in vitro, such as routine storage of platelets, and explore the role of reactive oxygen species (ROS) involved in the regulation of platelet autophagy. The ROS and autophagy levels of platelet concentrates from apheresis platelets were evaluated through flow cytometry. The expression levels of autophagy-associated proteins (LC3I, LC3II, Beclin1, Parkin, and PINK1) were measured via Western blot. All biomarkers were dynamically monitored for seven days. Moreover, the morphological characteristics of platelet morphology during storage were analyzed through transmission electron microscopy (TEM). Flow cytometry showed that the levels of total cell ROS and mitochondria ROS increased in the stored platelets. Together with the increase in mitochondrial ROS, the autophagy signal LC3 in the platelets was strongly amplified. The number of swollen platelets (large platelets) considerably increased, and that of autophagy signal LC3 was remarkably higher than that of the normal platelets. Western blot revealed that the expression levels of Beclin1 and LC3 II/LC3 I ratio were enhanced, whereas those of Parkin and PINK1 almost did not change during the seven days of storage. The existence of autophagosomes or autophagolysosomes in the platelets at the middle stage of platelet storage was observed via TEM. Our data demonstrated that the subpopulation of large (swollen) platelets exhibited different autophagy patterns. Furthermore, increased platelet autophagy was associated with mitochondrial ROS. These preliminary results suggest that swelling platelets have a higher autophagy pattern than normal platelets during storage.
Literatur
1.
Zurück zum Zitat Jurk K, Kehre BE (2005) Platelets: physiology and biochemistry. Semin Thromb Hemost 31(4):381–392CrossRefPubMed Jurk K, Kehre BE (2005) Platelets: physiology and biochemistry. Semin Thromb Hemost 31(4):381–392CrossRefPubMed
2.
Zurück zum Zitat Andrews RK, Berndt MC (2004) Platelet physiology and thrombosis. Thromb Res 114(5–6):447–453CrossRefPubMed Andrews RK, Berndt MC (2004) Platelet physiology and thrombosis. Thromb Res 114(5–6):447–453CrossRefPubMed
3.
4.
Zurück zum Zitat Scherz-Shouval R, Shvets E, Fass E, Shorer H, Gil L, Elazar Z (2007) Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J 26(7):1749–1760CrossRefPubMedPubMedCentral Scherz-Shouval R, Shvets E, Fass E, Shorer H, Gil L, Elazar Z (2007) Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J 26(7):1749–1760CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Ghasemzadeh M, Hosseini E (2017) Platelet granule release is associated with reactive oxygen species generation during platelet storage: a direct link between platelet pro-inflammatory and oxidation states. Thromb Res 156:101–104CrossRefPubMed Ghasemzadeh M, Hosseini E (2017) Platelet granule release is associated with reactive oxygen species generation during platelet storage: a direct link between platelet pro-inflammatory and oxidation states. Thromb Res 156:101–104CrossRefPubMed
6.
Zurück zum Zitat Vucic M, Stanojkovic Z, Antic A, Vucic J, Pavlovic V (2018) Evaluation of platelet activation in leukocyte-depleted platelet concentrates during storage. Bosn J Basic Med Sci 18(1):29–34PubMedPubMedCentral Vucic M, Stanojkovic Z, Antic A, Vucic J, Pavlovic V (2018) Evaluation of platelet activation in leukocyte-depleted platelet concentrates during storage. Bosn J Basic Med Sci 18(1):29–34PubMedPubMedCentral
7.
8.
Zurück zum Zitat Ohto H, Nollet KE (2011) Overview on platelet preservation: better controls over storage lesion. Transfus Apher Sci 44(3):321–325CrossRefPubMed Ohto H, Nollet KE (2011) Overview on platelet preservation: better controls over storage lesion. Transfus Apher Sci 44(3):321–325CrossRefPubMed
9.
Zurück zum Zitat Ouseph MM, Huang Y, Banerjee M, Joshi S, MacDonald L, Zhong Y, Liu H, Li X, Xiang B, Zhang G, Komatsu M, Yue Z, Li Z, Storrie B, Whiteheart SW, Wang QJ (2015) Autophagy is induced upon platelet activation and is essential for hemostasis and thrombosis. Blood 126(10):1224–1233CrossRefPubMedPubMedCentral Ouseph MM, Huang Y, Banerjee M, Joshi S, MacDonald L, Zhong Y, Liu H, Li X, Xiang B, Zhang G, Komatsu M, Yue Z, Li Z, Storrie B, Whiteheart SW, Wang QJ (2015) Autophagy is induced upon platelet activation and is essential for hemostasis and thrombosis. Blood 126(10):1224–1233CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Cao Y, Cai J, Zhang S, Yuan N, Li X, Fang Y, Song L, Shang M, Liu S, Zhao W, Hu S, Wang J (2015) Loss of autophagy leads to failure in megakaryopoiesis, megakaryocyte differentiation, and thrombopoiesis in mice. Exp Hematol 43:488–494CrossRefPubMed Cao Y, Cai J, Zhang S, Yuan N, Li X, Fang Y, Song L, Shang M, Liu S, Zhao W, Hu S, Wang J (2015) Loss of autophagy leads to failure in megakaryopoiesis, megakaryocyte differentiation, and thrombopoiesis in mice. Exp Hematol 43:488–494CrossRefPubMed
11.
Zurück zum Zitat Lee SH, Du J, Stitham J, Atteya G, Lee S, Xiang Y, Wang D, Jin Y, Leslie K, Spollett G, Srivastava A, Mannam P, Ostriker A, Martin KA, Tang WH, Hwa J (2016) Inducing mitophagy in diabetic platelets protects against severe oxidative stress. EMBO Mol Med 8(7):779–795CrossRefPubMedPubMedCentral Lee SH, Du J, Stitham J, Atteya G, Lee S, Xiang Y, Wang D, Jin Y, Leslie K, Spollett G, Srivastava A, Mannam P, Ostriker A, Martin KA, Tang WH, Hwa J (2016) Inducing mitophagy in diabetic platelets protects against severe oxidative stress. EMBO Mol Med 8(7):779–795CrossRefPubMedPubMedCentral
12.
15.
Zurück zum Zitat Mangalpally KK, Siqueiros-Garcia A, Vaduganathan M, Dong JF, Kleiman NS, Guthikonda S (2010) Platelet activation patterns in platelet size sub-populations: differential responses to aspirin in vitro. J Thromb Thrombolysis 30(3):251–262CrossRefPubMed Mangalpally KK, Siqueiros-Garcia A, Vaduganathan M, Dong JF, Kleiman NS, Guthikonda S (2010) Platelet activation patterns in platelet size sub-populations: differential responses to aspirin in vitro. J Thromb Thrombolysis 30(3):251–262CrossRefPubMed
16.
Zurück zum Zitat Eng KE, Panas MD, Karlsson Hedestam GB, McInerney GM (2010) A novel quantitative flow cytometry-based assay for autophagy. Autophagy 6(5):634–641CrossRefPubMed Eng KE, Panas MD, Karlsson Hedestam GB, McInerney GM (2010) A novel quantitative flow cytometry-based assay for autophagy. Autophagy 6(5):634–641CrossRefPubMed
17.
Zurück zum Zitat Neumüller J, Meisslitzer-Ruppitsch C, Ellinger A, Pavelkaa M, Jungbauerb C, Renzb R, Leitnerc G, Wagner T (2013) Monitoring of platelet activation in platelet concentrates using transmission electron microscopy. Transfus Med Hemother 40(2):101–107CrossRefPubMedPubMedCentral Neumüller J, Meisslitzer-Ruppitsch C, Ellinger A, Pavelkaa M, Jungbauerb C, Renzb R, Leitnerc G, Wagner T (2013) Monitoring of platelet activation in platelet concentrates using transmission electron microscopy. Transfus Med Hemother 40(2):101–107CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Lee J, Giordano S, Zhang J (2012) Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling. Biochem J 441(2):523–540CrossRefPubMed Lee J, Giordano S, Zhang J (2012) Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling. Biochem J 441(2):523–540CrossRefPubMed
19.
Zurück zum Zitat Luo XL, Jiang JY, Huang Z, Chen LX (2019) Autophagic regulation of platelet biology. J Cell Physiol 234(9):14483–14488CrossRefPubMed Luo XL, Jiang JY, Huang Z, Chen LX (2019) Autophagic regulation of platelet biology. J Cell Physiol 234(9):14483–14488CrossRefPubMed
20.
Zurück zum Zitat Al Amir Dache Z, Otandault A, Tanos R, Pastor B, Meddeb R, Sanchez C, Arena G, Lasorsa L, Bennett A, Grange T, El Messaoudi S, Mazard T, Prevostel C, Thierry AR (2020) Blood contains circulating cell-free respiratory competent mitochondria. FASEB J 34(3):3616–3630CrossRefPubMed Al Amir Dache Z, Otandault A, Tanos R, Pastor B, Meddeb R, Sanchez C, Arena G, Lasorsa L, Bennett A, Grange T, El Messaoudi S, Mazard T, Prevostel C, Thierry AR (2020) Blood contains circulating cell-free respiratory competent mitochondria. FASEB J 34(3):3616–3630CrossRefPubMed
21.
Zurück zum Zitat Zhou H, Li D, Zhu P, Hu S, Hu N, Ma S, Zhang Y, Han T, Ren J, Cao F, Chen Y (2017) Melatonin suppresses platelet activation and function against cardiac ischemia/reperfusion injury via PPARgamma/FUNDC1/mitophagy pathways. J Pineal Res 63(4):e12438CrossRef Zhou H, Li D, Zhu P, Hu S, Hu N, Ma S, Zhang Y, Han T, Ren J, Cao F, Chen Y (2017) Melatonin suppresses platelet activation and function against cardiac ischemia/reperfusion injury via PPARgamma/FUNDC1/mitophagy pathways. J Pineal Res 63(4):e12438CrossRef
22.
Zurück zum Zitat Zhang W, Ren H, Xu C, Zhu C, Wu H, Liu D, Wang J, Liu L, Li W, Ma Q, Du L, Zheng M, Zhang C, Liu J, Chen Q (2016) Hypoxic mitophagy regulates mitochondrial quality and platelet activation and determines severity of I/R heart injury. Elife 5:e21407CrossRefPubMedPubMedCentral Zhang W, Ren H, Xu C, Zhu C, Wu H, Liu D, Wang J, Liu L, Li W, Ma Q, Du L, Zheng M, Zhang C, Liu J, Chen Q (2016) Hypoxic mitophagy regulates mitochondrial quality and platelet activation and determines severity of I/R heart injury. Elife 5:e21407CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Yu L, McPhee CK, Zheng L, Mardones GA, Rong Y, Peng J, Mi N, Zhao Y, Liu Z, Wan F, Hailey DW, Oorschot V, Klumperman J, Baehrecke EH, Lenardo MJ (2010) Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature 465(7300):942–946CrossRefPubMedPubMedCentral Yu L, McPhee CK, Zheng L, Mardones GA, Rong Y, Peng J, Mi N, Zhao Y, Liu Z, Wan F, Hailey DW, Oorschot V, Klumperman J, Baehrecke EH, Lenardo MJ (2010) Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature 465(7300):942–946CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Portal-Núñez S, Esbrit P, Alcaraz MJ, Largo R (2016) Oxidative stress, autophagy, epigenetic changes and regulation by miRNAs as potential therapeutic targets in osteoarthritis. Biochem Pharmacol 108:1–10CrossRefPubMed Portal-Núñez S, Esbrit P, Alcaraz MJ, Largo R (2016) Oxidative stress, autophagy, epigenetic changes and regulation by miRNAs as potential therapeutic targets in osteoarthritis. Biochem Pharmacol 108:1–10CrossRefPubMed
25.
Zurück zum Zitat Tang H, Gao M, Fu Y, Gui R, Ma X (2020) The effect of autophagic activity on the function of apheresis platelets and on the efficacy of clinical platelet transfusion. Transfus Med Hemother 47(4):302–313CrossRefPubMedPubMedCentral Tang H, Gao M, Fu Y, Gui R, Ma X (2020) The effect of autophagic activity on the function of apheresis platelets and on the efficacy of clinical platelet transfusion. Transfus Med Hemother 47(4):302–313CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Sui X, Kong N, Ye L, Han W, Zhou J, Zhang Q, He C, Pan H (2014) p38 and JNK MAPK pathways control the balance of apoptosis and autophagy in response to chemotherapeutic agents. Cancer Lett 344(2):174–179CrossRefPubMed Sui X, Kong N, Ye L, Han W, Zhou J, Zhang Q, He C, Pan H (2014) p38 and JNK MAPK pathways control the balance of apoptosis and autophagy in response to chemotherapeutic agents. Cancer Lett 344(2):174–179CrossRefPubMed
27.
Zurück zum Zitat Davis CH, Kim KY, Bushong EA, Mills EA, Boassa D, Shih T, Kinebuchi M, Phan S, Zhou Y, Bihlmeyer NA, Nguyen JV, Jin Y, Ellisman MH, Marsh-Armstrong N (2014) Transcellular degradation of axonal mitochondria. Proc Natl Acad Sci U S A 111(26):9633–9638CrossRefPubMedPubMedCentral Davis CH, Kim KY, Bushong EA, Mills EA, Boassa D, Shih T, Kinebuchi M, Phan S, Zhou Y, Bihlmeyer NA, Nguyen JV, Jin Y, Ellisman MH, Marsh-Armstrong N (2014) Transcellular degradation of axonal mitochondria. Proc Natl Acad Sci U S A 111(26):9633–9638CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Torralba D, Baixauli F, Sánchez-Madrid F (2016) Mitochondria know no boundaries: mechanisms and functions of intercellular mitochondrial transfer. Front Cell Dev Biol 4:107CrossRefPubMedPubMedCentral Torralba D, Baixauli F, Sánchez-Madrid F (2016) Mitochondria know no boundaries: mechanisms and functions of intercellular mitochondrial transfer. Front Cell Dev Biol 4:107CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat McWilliams TG, Barini E, Pohjolan-Pirhonen R, Brooks SP, Singh F, Burel S, Balk K, Kumar A, Montava-Garriga L, Prescott AR, Hassoun SM, Mouton-Liger F, Ball G, Hills R, Knebel A, Ulusoy A, Di Monte DA, Tamjar J, Antico O, Fears K, Smith L, Brambilla R, Palin E, Valori M, Eerola-Rautio J, Tienari P, Corti O, Dunnett SB, Ganley IG, Suomalainen A, Muqit MMK (2018) Phosphorylation of Parkin at serine 65 is essential for its activation in vivo. Open Biol 8(11):180108CrossRefPubMedPubMedCentral McWilliams TG, Barini E, Pohjolan-Pirhonen R, Brooks SP, Singh F, Burel S, Balk K, Kumar A, Montava-Garriga L, Prescott AR, Hassoun SM, Mouton-Liger F, Ball G, Hills R, Knebel A, Ulusoy A, Di Monte DA, Tamjar J, Antico O, Fears K, Smith L, Brambilla R, Palin E, Valori M, Eerola-Rautio J, Tienari P, Corti O, Dunnett SB, Ganley IG, Suomalainen A, Muqit MMK (2018) Phosphorylation of Parkin at serine 65 is essential for its activation in vivo. Open Biol 8(11):180108CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Okatsu K, Oka T, Iguchi M, Imamura K, Kosako H, Tani N, Kimura M, Go E, Koyano F, Funayama M, Shiba-Fukushima K, Sato S, Shimizu H, Fukunaga Y, Taniguchi H, Komatsu M, Hattori N, Mihara K, Tanaka K, Matsuda N (2012) PINK1 autophosphorylation upon membrane potential dissipation is essential for Parkin recruitment to damaged mitochondria. Nat Commun. 3:1016CrossRefPubMed Okatsu K, Oka T, Iguchi M, Imamura K, Kosako H, Tani N, Kimura M, Go E, Koyano F, Funayama M, Shiba-Fukushima K, Sato S, Shimizu H, Fukunaga Y, Taniguchi H, Komatsu M, Hattori N, Mihara K, Tanaka K, Matsuda N (2012) PINK1 autophosphorylation upon membrane potential dissipation is essential for Parkin recruitment to damaged mitochondria. Nat Commun. 3:1016CrossRefPubMed
31.
Zurück zum Zitat Hayakawa K, Esposito E, Wang X, Terasaki Y, Liu Y, Xing C, Ji X, Lo EH (2016) Transfer of mitochondria from astrocytes to neurons after stroke. Nature 535(7613):551–555CrossRefPubMedPubMedCentral Hayakawa K, Esposito E, Wang X, Terasaki Y, Liu Y, Xing C, Ji X, Lo EH (2016) Transfer of mitochondria from astrocytes to neurons after stroke. Nature 535(7613):551–555CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Jiao H, Jiang D, Hu X, Du W, Ji L, Yang Y, Li X, Sho T, Wang X, Li Y, Wu YT, Wei YH, Hu X, Yu L (2021) Mitocytosis, a migrasome-mediated mitochondrial quality-control process. Cell 184(11):2896–2910CrossRefPubMed Jiao H, Jiang D, Hu X, Du W, Ji L, Yang Y, Li X, Sho T, Wang X, Li Y, Wu YT, Wei YH, Hu X, Yu L (2021) Mitocytosis, a migrasome-mediated mitochondrial quality-control process. Cell 184(11):2896–2910CrossRefPubMed
33.
Zurück zum Zitat Marcoux G, Duchez AC, Rousseau M, Lévesque T, Boudreau LH, Thibault L, Boilard E (2017) Microparticle and mitochondrial release during extended storage of different types of platelet concentrates. Platelets 28(3):272–280CrossRefPubMed Marcoux G, Duchez AC, Rousseau M, Lévesque T, Boudreau LH, Thibault L, Boilard E (2017) Microparticle and mitochondrial release during extended storage of different types of platelet concentrates. Platelets 28(3):272–280CrossRefPubMed
35.
Zurück zum Zitat Ghasemzadeh M, Hosseini E, Roudsari O, Zadkhak P (2018) Intraplatelet reactive oxygen species (ROS) correlate with the shedding of adhesive receptors, microvesiculation and platelet adhesion to collagen during storage: does endogenous ROS generation downregulate platelet adhesive function? Thromb Res 163:153–161CrossRefPubMed Ghasemzadeh M, Hosseini E, Roudsari O, Zadkhak P (2018) Intraplatelet reactive oxygen species (ROS) correlate with the shedding of adhesive receptors, microvesiculation and platelet adhesion to collagen during storage: does endogenous ROS generation downregulate platelet adhesive function? Thromb Res 163:153–161CrossRefPubMed
36.
Zurück zum Zitat Hosseini E, Hojjati S, Afzalniaye Gashti S, Ghasemzadeh M (2020) Collagen-dependent platelet dysfunction and its relevance to either mitochondrial ROS or cytosolic superoxide generation: a question about the quality and functional competence of long-stored platelets. Thromb J 18(1):18CrossRefPubMedPubMedCentral Hosseini E, Hojjati S, Afzalniaye Gashti S, Ghasemzadeh M (2020) Collagen-dependent platelet dysfunction and its relevance to either mitochondrial ROS or cytosolic superoxide generation: a question about the quality and functional competence of long-stored platelets. Thromb J 18(1):18CrossRefPubMedPubMedCentral
37.
Zurück zum Zitat Tyagi T, Jain K, Gu S, Qiu M, Gu V, Melchinger H, Rinder H, Martin K, Gardiner E, Lee A, Tang W, Hwa J (2022) A guide to molecular and functional investigations of platelets to bridge basic and clinical sciences. Nat Cardiovasc Res 1:223–237CrossRefPubMedPubMedCentral Tyagi T, Jain K, Gu S, Qiu M, Gu V, Melchinger H, Rinder H, Martin K, Gardiner E, Lee A, Tang W, Hwa J (2022) A guide to molecular and functional investigations of platelets to bridge basic and clinical sciences. Nat Cardiovasc Res 1:223–237CrossRefPubMedPubMedCentral
38.
Zurück zum Zitat Vučetić D, Ilić V, Vojvodić D, Subota V, Todorović M, Balint B (2018) Flow cytometry analysis of platelet populations: usefulness for monitoring the storage lesion in pooled buffy-coat platelet concentrates. Blood Transfus 16(1):83–92PubMedPubMedCentral Vučetić D, Ilić V, Vojvodić D, Subota V, Todorović M, Balint B (2018) Flow cytometry analysis of platelet populations: usefulness for monitoring the storage lesion in pooled buffy-coat platelet concentrates. Blood Transfus 16(1):83–92PubMedPubMedCentral
Metadaten
Titel
High Autophagy Patterns in Swelling Platelets During Apheresis Platelet Storage
verfasst von
Lu Yu
Shifang Yu
Yunlei He
Gang Deng
Qiang Li
Publikationsdatum
08.03.2023
Verlag
Springer India
Erschienen in
Indian Journal of Hematology and Blood Transfusion / Ausgabe 4/2023
Print ISSN: 0971-4502
Elektronische ISSN: 0974-0449
DOI
https://doi.org/10.1007/s12288-023-01638-1

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