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C2C12 myoblasts release micro-vesicles containing mtDNA and proteins involved in signal transduction
Abstract
Micro-vesicles can be released by different cell types and operate as 'safe containers' mediating inter-cellular communication. In this work we investigated whether cultured myoblasts could release exosomes. The reported data demonstrate, for the first time, that C2C12 myoblasts release micro-vesicles as shown by the presence of two exosome markers (Tsg101 and Alix proteins). Using real-time PCR analysis it was shown that these micro-vesicles, like other cell types, carry mtDNA. Proteomic characterization of the released micro-vesicle contents showed the presence of many proteins involved in signal transduction. The bioinformatics assessment of the Disorder Index and Aggregation Index of these proteins suggested that C2C12 micro-vesicles mainly deliver the machinery for signal transduction to target cells rather than key proteins involved in hub functions in molecular networks. The presence of IGFBP-5 in the purified micro-vesicles represents an exception, since this binding protein can play a key role in the modulation of the IGF-1 signalling pathway. In conclusion, the present findings demonstrate that skeletal muscle cells release micro-vesicles, which probably have an important role in the communication processes within skeletal muscles and between skeletal muscles and other organs. In particular, the present findings suggest possible new diagnostic approaches to skeletal muscle diseases.
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“Interestingly, mitochondrial DNA (Guescini et al., 2010), histones, and nuclear proteins were also found in ELV-MB (Guescini et al., 2010; Forterre et al., 2014a; Sork et al., 2018) and ELV-MT (Le Bihan et al., 2012; Forterre et al., 2014a).”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Guescini et al., 2010
In the citing paper
“It has been described that myoblasts produce small ELVs (ELV-MB) (Guescini et al., 2010; Forterre et al., 2014a,b; Sork et al., 2018) likely reflecting the intense macromolecule/RNA/lipids turn-over that occurs during cell proliferation (Johnstone et al., 1991; Desdin-Mico and Mittelbrunn, 2017).”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Guescini et al., 2010
In the citing paper
“During the last decade, it has been shown that muscle cells also release extracellular vesicles (EVs) into the extracellular milieu, which represent new paracrine and endocrine signals that have modified our conceptual basis to explain how muscles communicate to other organs (Guescini et al., 2010; Le Bihan et al., 2012; Romancino et al., 2013; Forterre et al., 2014a).”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Guescini et al., 2010
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1 retracted
THIS ARTICLE HAS BEEN RETRACTED Exercise induces interleukin‐8 expression in human skeletal muscle
Akerstrom, T. C. A., Steensberg, A., Keller, P., Keller, C., Penkowa, M., & Pedersen, B. K. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.077610 · Cited by 130
RetractedCleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961
Mass Spectrometric Sequencing of Proteins from Silver-Stained Polyacrylamide Gels
Shevchenko, A., Wilm, M. S., Vorm, O., & Mann, M. (1996) · Analytical Chemistry · doi:10.1021/ac950914h · Cited by 8,996
Exosomes: composition, biogenesis and function
Théry, C., Zitvogel, L., & Amigorena, S. (2002) · Nature reviews. Immunology · doi:10.1038/nri855 · Cited by 5,355
Intrinsically unstructured proteins and their functions
Dyson, H. J., & Wright, P. E. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1589 · Cited by 3,871
Exosomes – vesicular carriers for intercellular communication
Simons, M., & Raposo, G. (2009) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.03.007 · Cited by 2,410
Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6
Pedersen, B. K., & Febbraio, M. A. (2008) · Physiological Reviews · doi:10.1152/physrev.90100.2007 · Cited by 2,388
Nanotubular Highways for Intercellular Organelle Transport
Rustom, A., Saffrich, R., Markovic, I., Walther, P., & Gerdes, H.-H. (2004) · Science · doi:10.1126/science.1093133 · Cited by 2,038
Shedding microvesicles: artefacts no more
Cocucci, E., Racchetti, G., & Meldolesi, J. (2009) · Trends in Cell Biology · doi:10.1016/j.tcb.2008.11.003 · Cited by 1,742
Intrinsically Disordered Proteins in Human Diseases: Introducing the D 2 Concept
Uversky, V. N., Oldfield, C. J., & Dunker, A. K. (2008) · Annual Review of Biophysics · doi:10.1146/annurev.biophys.37.032807.125924 · Cited by 1,447
Linding, R., Jensen, L. J., Diella, F., Bork, P., Gibson, T. J., & Russell, R. B. (2003) · Structure · doi:10.1016/j.str.2003.10.002 · Cited by 1,235
Protein aggregation: folding aggregates, inclusion bodies and amyloid
Fink, A. L. (1998) · Folding and Design · doi:10.1016/s1359-0278(98)00002-9 · Cited by 1,179
Exosomes: proteomic insights and diagnostic potential
Simpson, R. J., Lim, J. W., Moritz, R. L., & Mathivanan, S. (2009) · Expert Review of Proteomics · doi:10.1586/epr.09.17 · Cited by 1,119
AGGRESCAN: a server for the prediction and evaluation of "hot spots" of aggregation in polypeptides
Conchillo‐Solé, O., de Groot, N. S., Avilés, F. X., Vendrell, J., Daura, X., & Ventura, S. (2007) · BMC Bioinformatics · doi:10.1186/1471-2105-8-65 · Cited by 1,077
GlobPlot: exploring protein sequences for globularity and disorder
Linding, R. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg519 · Cited by 1,009
Exosomes: A Common Pathway for a Specialized Function
van Niel, G., Porto-Carreiro, I., Simoes, S., & Raposo, G. (2006) · The Journal of Biochemistry · doi:10.1093/jb/mvj128 · Cited by 922
Exosomes are released by cultured cortical neurones
Fauré, J., Lachenal, G., Court, M., Hirrlinger, J., Chatellard-Causse, C., Blot, B., Grange, J., Schoehn, G., Goldberg, Y., Boyer, V., et al. (2006) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2005.12.003 · Cited by 896
Exosomes: endosomal-derived vesicles shipping extracellular messages
Février, B., & Raposo, G. (2004) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2004.06.003 · Cited by 881
Muscle‐derived interleukin‐6: mechanisms for activation and possible biological roles
FEBBRAIO, M. A., & PEDERSEN, B. K. (2002) · The FASEB Journal · doi:10.1096/fj.01-0876rev · Cited by 875
Exosomes: From biogenesis and secretion to biological function
Keller, S., Sanderson, M. P., Stoeck, A., & Altevogt, P. (2006) · Immunology Letters · doi:10.1016/j.imlet.2006.09.005 · Cited by 856
Exosome Function: From Tumor Immunology to Pathogen Biology
Schorey, J. S., & Bhatnagar, S. (2008) · Traffic · doi:10.1111/j.1600-0854.2008.00734.x · Cited by 766
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Guescini, M., Genedani, S., Stocchi, V., & Agnati, L. F. (2009) · Journal of Neural Transmission · doi:10.1007/s00702-009-0288-8 · Cited by 662
Searching for the exercise factor: is IL-6 a candidate?
Pedersen (2003) · Journal of Muscle Research and Cell Motility · doi:10.1023/a:1026070911202 · Cited by 564
Pasternack, B. S., & Colquhoun, D. (1972) · Journal of the American Statistical Association · doi:10.2307/2284489 · Cited by 550
Protein sorting into multivesicular endosomes
Raiborg, C., Rusten, T. E., & Stenmark, H. (2003) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(03)00080-2 · Cited by 500
Interleukin-6 Is a Novel Factor Mediating Glucose Homeostasis During Skeletal Muscle Contraction
Febbraio, M. A., Hiscock, N., Sacchetti, M., Fischer, C. P., & Pedersen, B. K. (2004) · Diabetes · doi:10.2337/diabetes.53.7.1643 · Cited by 455
FGF21 is an Akt‐regulated myokine
Izumiya, Y., Bina, H. A., Ouchi, N., Akasaki, Y., Kharitonenkov, A., & Walsh, K. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.10.021 · Cited by 415
Identification and functions of usefully disordered proteins
Dunker, A. K., Brown, C. J., & Zoran Obradovic, A. (2002) · Advances in protein chemistry · doi:10.1016/s0065-3233(02)62004-2 · Cited by 410
Itinerant exosomes: emerging roles in cell and tissue polarity
Lakkaraju, A., & Rodriguez-Boulan, E. J. (2008) · Trends in Cell Biology · doi:10.1016/j.tcb.2008.03.002 · Cited by 408
Roles of insulin-like growth factor (IGF) binding proteins in regulating IGF actions
Duan, C., & Xu, Q. (2005) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2004.12.022 · Cited by 354
Ouchi, N., Oshima, Y., Ohashi, K., Higuchi, A., Ikegami, C., Izumiya, Y., & Walsh, K. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803440200 · Cited by 338
Tunneling nanotubes: A new route for the exchange of components between animal cells
Gerdes, H.-H., Bukoreshtliev, N. V., & Barroso, J. F. V. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.03.071 · Cited by 304
The metabolic role of IL-6 produced during exercise: is IL-6 an exercise factor?
Pedersen, B. K., Steensberg, A., Fischer, C. P., Keller, C., Keller, P., Plomgaard, P., Petersen, E. W., & Febbraio, M. A. (2004) · Proceedings of The Nutrition Society · doi:10.1079/pns2004338 · Cited by 279
Mallegol, J., van Niel, G., Lebreton, C., Lepelletier, Y., Candalh, C., Dugave, C., Heath, J. K., Raposo, G., Cerf–Bensussan, N., & Heyman, M. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.02.043 · Cited by 271
Nielsen, A. R., Mounier, R., Plomgaard, P., Mortensen, O. H., Penkowa, M., Speerschneider, T., Pilegaard, H., & Pedersen, B. K. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.139618 · Cited by 266
Exosomal transfer of proteins and RNAs at synapses in the nervous system
Smalheiser, N. R. (2007) · Biology Direct · doi:10.1186/1745-6150-2-35 · Cited by 256
Edward F. Adolph Distinguished Lecture: Muscle as an endocrine organ: IL-6 and other myokines
Pedersen, B. K. (2009) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00734.2009 · Cited by 221
Prediction of "hot spots" of aggregation in disease-linked polypeptides
de Groot, N. S., Pallarès, I., Avilés, F. X., Vendrell, J., & Ventura, S. (2005) · BMC Structural Biology · doi:10.1186/1472-6807-5-18 · Cited by 211
Herbst, A., Pak, J. W., McKenzie, D., Bua, E., Bassiouni, M., & Aiken, J. M. (2007) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/62.3.235 · Cited by 200
Belting, M., & Wittrup, A. (2008) · The Journal of Cell Biology · doi:10.1083/jcb.200810038 · Cited by 163
Chan, S. M. H., Carey, A. L., Watt, M. J., & Febbraio, M. A. (2004) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00030.2004 · Cited by 158
Specifying the cellular responses to IGF signals: roles of IGF-binding proteins
Duan, C. (2002) · Journal of Endocrinology · doi:10.1677/joe.0.1750041 · Cited by 149
Mitochondrial DNA mutations and aging: devils in the details?
Khrapko, K., & Vijg, J. (2009) · Trends in Genetics · doi:10.1016/j.tig.2008.11.007 · Cited by 112
Koulintchenko, M. V., Temperley, R., Mason, P. A., Dietrich, A., & Lightowlers, R. N. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi435 · Cited by 89
Bdnf expression in rat skeletal muscle after acute or repeated exercise.
Cuppini, R., Sartini, S., Agostini, D., Guescini, M., Ambrogini, P., Betti, M., Bertini, L., Vallasciani, M., & Stocchi, V. (2007) · PubMed · doi:10.4449/aib.v145i2.868 · Cited by 63
Zeev‐Ben‐Mordehai, T., Rydberg, E. H., Solomon, A., Toker, L., Auld, V. J., Silman, I., Botti, S. A., & Sussman, J. L. (2003) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.10471 · Cited by 58
Agnati, L. F., Leo, G., Genedani, S., Andreoli, N., Marcellino, D. J., Woods, A. S., Piron, L., Guidolin, D., & Fuxé, K. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.10.003 · Cited by 43
Agnati, L. F., Guidolin, D., Baluška, F., Barlow, P. W., Carone, C., & Genedani, S. (2010) · Current Alzheimer Research · doi:10.2174/156720510791162395 · Cited by 37
Choi, Y.-S., RYU, B., Min, H., Lee, S., & Pak, Y. K. (2005) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1338.009 · Cited by 33
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Metadata
- Authors
- Guescini, M., Guidolin, D., Vallorani, L., Casadei, L., Gioacchini, A. M., Tibollo, P., Battistelli, M., Falcieri, E., Battistin, L., Agnati, L. F., & Stocchi, V.
- Affiliations
- University of Urbino (IT)
- University of Padua (IT)
- IRCCS San Camillo Hospital (IT)
- Corresponding author
- Guescini, M.
- Stocchi, V.
- ORCID
- Venue
- Experimental Cell Research
- Publisher
- Elsevier BV
- Published
- 2010-07
- Volume
- 316
- Issue
- 12
- Pages
- 1977-1984
- ISSN
- 0014-4827 (ISSN-L)
- OpenAlex
- W1981888677
- Cited by
- 294
- References
- 51
- Citations by year
- 2026: 2 · 2025: 16 · 2024: 21 · 2023: 33 · 2022: 27 · 2021: 27 · 2020: 32 · 2019: 25 · 2018: 9 · 2017: 29 · 2016: 14 · 2015: 20 · 2014: 17 · 2013: 12 · 2012: 5
- FWCI
- 2.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Experimental Cell Research (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutional Research information system (University of Urbino) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
- Keywords
- exosomes, C2C12 myoblasts, mitochondrial DNA, signal transduction proteins, TSG101, Alix, IGFBP-5, IGF-1 signaling, intercellular communication, skeletal muscle, exosomal proteome, skeletal muscle disorders
- MeSH terms
- Tsg101 Protein, Animals, Calcium-Binding Proteins, Cells, Cultured, DNA-Binding Proteins, DNA, Mitochondrial, Insulin-Like Growth Factor I, Transcription Factors, Signal Transduction, Insulin-Like Growth Factor Binding Protein 5, Myoblasts, Skeletal, Microscopy, Electron, Transmission, Mice, Endosomal Sorting Complexes Required for Transport
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