Genomic and Epigenomic Biomarkers of Toxicology and Disease - Группа авторов

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workers with occupational lead exposure. Biosci. Rep. 37.

      159 Yamamoto, M., Singh, A., Sava, F., Pui, M., Tebbutt, S.J., and Carlsten, C. (2013). MicroRNA expression in response to controlled exposure to diesel exhaust: Attenuation by the antioxidant N-acetylcysteine in a randomized crossover study. Environ. Health Perspect. 121: 670–675.

      160 Yanshina, D.D., Kossinova, O.A., Gopanenko, A.V., Krasheninina, O.A., Malygin, A.A., Venyaminova, A.G., and Karpova, G.G. (2018). Structural features of the interaction of the 3ʹ-untranslated region of mRNA containing exosomal RNA-specific motifs with YB-1, a potential mediator of mRNA sorting. Biochimie. 144: 134–143.

      161 Yauk, C.L., Rowan-carroll, A., Stead, J.D., and Williams, A. (2010). Cross-platform analysis of global microRNA expression technologies. BMC Genom. 11: 330.

      162 Yu, H.W. and Cho, W.C. (2015). The role of microRNAs in toxicology. Arch. Toxicol. 89: 319–325.

      163 Yuan, H., Yuan, M., Tang, Y., Wang, B., and Zhan, X. (2018). MicroRNA expression profiling in human acute organophosphorus poisoning and functional analysis of dysregulated miRNAs. Afr. Health Sci. 18: 333–342.

      164 Zhang, Y., Liu, D., Chen, X., Li, J., Li, L., Bian, Z., Sun, F., Lu, J., Yin, Y., Cai, X., Sun, Q., Wang, K., Ba, Y., Wang, Q., Wang, D., Yang, J., Liu, P., Xu, T., Yan, Q., Zhang, J., Zen, K., and Zhang, C.Y. (2010). Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol. Cell 39: 133–144.

      165 Zhou, S.S., Jin, J.P., Wang, J.Q., Zhang, Z.G., Freedman, J.H., Zheng, Y., and Cai, L. (2018). miRNAS in cardiovascular diseases: Potential biomarkers, therapeutic targets and challenges. Acta Pharmacol. Sin. 39: 1073–1084.

      166 Zhou, X., Wang, L., Zou, W., Chen, X., Roizman, B., and Zhou, G.G. (2020). hnRNPA2B1 Associated with recruitment of RNA into exosomes plays a key role in herpes simplex virus 1 release from infected cells. J. Virol. 94 (3): e00367-20.

       Ryuichi Ono1*, Yusuke Yoshioka2, Yusuke Furukawa1, Mie Naruse1,3, Makiko Kuwagata1, Takahiro Ochiya1,2,4, Satoshi Kitajima1, and Yoko Hirabayashi5

       1 Division of Cellular and Molecular Toxicology, Center for Biological Safety and Research, National Institute of Health Sciences (NIHS)

       2 Division of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University

       3 Central Animal Division, National Cancer Center Research Institute

       4 Division of Molecular and Cellular Medicine, National Cancer Center Research Institute

       5 Center for Biological Safety and Research, National Institute of Health Sciences (NIHS)

      Introduction

      Exosomes were originally discovered in 1983, as membrane vesicles of approximately 100 nm in diameter with a lipid bilayer structure. These vesicles are secreted by reticulocytes (Harding and Stahl 1983; Pan and Johnstone 1983). They were initially thought to be a “trash bag” in which cells could eliminate excess proteins; however, from 2007 on great advances in exosome research were made, as it was shown that microRNAs (miRNAs) in exosomes could be transferred between cells and played important roles in many physiological and pathological processes (Valadi et al. 2007; Pegtel et al. 2010; Mittelbrunn et al. 2011; Hergenreider et al. 2012; Montecalvo et al. 2012).

      Exosomes are secreted into body fluids from various types of cells and organs. Recent studies have demonstrated that exosomes secreted by tumor cells are transported to surrounding cells and participate in metastasis and infiltration. Since these tumor-derived exosomes containing cancer cell-specific miRNAs and mRNAs are secreted into body fluids such as blood, urine, ascites, amniotic fluid, bronchoalveolar lavage, and tears, the miRNAs and mRNAs in cancer cell-derived exosomes have come to be used as diagnostic biomarkers for early stage cancers (Thery et al. 2002; Logozzi et al. 2009; Lu et al. 2009; Rabinowits et al. 2009; Montecalvo et al. 2012; Peinado et al. 2012). In parallel, miRNAs contained in exosomes released into the blood from tissues and organs in response to adverse events, such as exposure to chemical substances and drugs, are expected to be useful as novel biomarkers for toxicity assessment.

      In this chapter we will introduce the latest findings on exosomes, including the newly appreciated biological significance of exosomes, and will explain the potential use of exosomes as biomarkers of toxicity.

      Figure 3.1 Schematic illustration of extracellular vesicles (EVs). EVs include exosomes, microvesicles and apoptotic bodies. MVB: multivesicular body.

      Exosomes are thought to derive from intraluminal vesicles through the fusion of an intermediate endocytic compartment, the multivesicular body (MVB), with the plasma membrane (Witwer et al. 2013; Cufaro et al. 2019). The MVB contains vesicles that bind either to lysosomes, to degrade their contents, or to the plasma membrane. The latter produces the release of intraluminal vesicles defined as exosomes into extracellular space (Harding and Stahl 1983; Pan et al. 1985).

      As already mentioned, exosomes are approximately 100 nm in diameter; hence they are smaller than MVs (Witwer et al. 2013). Exosome membrane proteins are enriched in heat shock proteins (HSP70, HSP90), integrins (LFA-1), proteins involved in MVB formation (ALIX, TSG101), tetraspanins (CD9, CD63, CD81, CD82, and CD151), immunostimulatory molecules (MHC class I/II proteins), lipid-related proteins, and phospholipases (Conde-vancells et al. 2008; Subra et al. 2010).

Exosomes Microvesicles Apoptotic Bodies
Origin Endocytic pathway Plasma membrane Plasma membrane
Size 40–120 nm 50–1000 nm 500–2000 nm
Function Intercellular communication Intercellular communication Facilitate phagocytosis
Markers Alix, Tsg101, tetraspanins Selectins, integrins, CD proteins, DNA, RNA40 ligand Histones, annexin V
Contents Protein, DNA, RNA Protein, DNA, RNA Nuclear

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