Abstract
Adenosine 5′-triphosphate (ATP) is implicated in intercellular communication as a neurotransmitter in the peripheral nervous system. In addition, ATP is known as lysosomal exocytosis activator. In this study, we investigated the role of extracellular ATP on demyelination during Wallerian degeneration (WD) using ex vivo and in vivo nerve degeneration models. We found that extracellular ATP inhibited myelin fragmentation and axonal degradation during WD. Furthermore, metformin and chlorpromazine, lysosomal exocytosis antagonists blocked the effect of ATP on the inhibition of demyelination. Thus, these findings indicate that ATP-induced-lysosomal exocytosis may be involved in demyelination during WD.
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References
Ansselin AD, Davey DF, Allen DG (1997) Extracellular ATP increases intracellular calcium in cultured adult Schwann cells. Neuroscience 76(3):947–955
Blott EJ, Griffiths GM (2002) Secretory lysosomes. Nat Rev Mol Cell Biol 3(2):122–131
Colomar A, Marty V, Médina C, Combe C, Parnet P, Amédée T (2003) Maturation and release of interleukin-1beta by lipopolysaccharide-primed mouse Schwann cells require the stimulation of P2X7 receptors. J Biol Chem 278(33):30732–30740
Dou Y, Wu HJ, Li HQ, Qin S, Wang YE, Li J, Lou HF, Chen Z, Li XM, Luo QM, Duan S (2012) Microglial migration mediated by ATP-induced ATP release from lysosomes. Cell Res 22(6):1022–1033
Dubový P (2011) Wallerian degeneration and peripheral nerve conditions for both axonal regeneration and neuropathic pain induction. Ann Anat 193(4):267–275
Elferink JG (1979) Chlorpromazine inhibits phagocytosis and exocytosis in rabbit polymorphonuclear leukocytes. Biochem Pharmacol 28(7):965–968
Friede RL, Meier T, Diem M (1981) How is the exact length of an internode determined? J Neurol Sci 50(2):217–228
Ghabriel MN, Allt G (1979a) The role of Schmidt-Lanterman incisures in Wallerian degeneration. I. A quantitative teased fibre study. Acta Neuropathol 48(2):83–93
Ghabriel MN, Allt G (1979b) The role of Schmidt-Lanterman incisures in Wallerian degeneration. II. An electron microscopic study. Acta Neuropathol 48(2):95–103
Grafe P, Schaffer V, Rucker F (2006) Kinetics of ATP release following compression injury of a peripheral nerve trunk. Purinergic Signal 2(3):527–536
Guertin AD, Zhang DP, Mak KS, Alberta JA, Kim HA (2005) Microanatomy of axon/glial signaling during Wallerian degeneration. J Neurosci 25(13):3478–3487
Holton P (1959) The liberation of adenosine triphosphate on antidromic stimulation of sensory nerves. J Physiol 145(3):494–504
Huynh C, Andrews NW (2005) The small chemical vacuolin-1 alters the morphology of lysosomes without inhibiting Ca2 + -regulated exocytosis. EMBO Rep 6(9):843–847
Jeftinija SD, Jeftinija KV (1998) ATP stimulates release of excitatory amino acids from cultured Schwann cells. Neuroscience 82(3):927–934
Jessen KR, Mirsky R (2008) Negative regulation of myelination: relevance for development, injury, and demyelinating disease. Glia 56(14):1552–1565
Jung J, Cai W, Jang SY, Shin YK, Suh DJ, Kim JK, Park HT (2011a) Transient lysosomal activation is essential for p75 nerve growth factor receptor expression in myelinated Schwann cells during Wallerian degeneration. Anat Cell Biol 44(1):41–49
Jung J, Cai W, Lee HK, Pellegatta M, Shin YK, Jang SY, Suh DJ, Wrabetz L, Feltri ML, Park HT (2011b) Actin polymerization is essential for myelin sheath fragmentation during Wallerian degeneration. J Neurosci 31(6):2009–2015
Jung J, Shin YH, Konishi H, Lee SJ, Kiyama H (2013) Possible ATP release through lysosomal exocytosis from primary sensory neurons. Biochem Biophys Res Commun 430(2):488–493
Labuzek K, Liber S, Gabryel B, Adamczyk J, Okopień B (2010) Metformin increases phagocytosis and acidifies lysosomal/endosomal compartments in AMPK-dependent manner in rat primary microglia. Naunyn Schmiedebergs Arch Pharmacol 381(2):171–186
Lazarowski ER, Boucher RC, Harden TK (2003) Mechanisms of release of nucleotides and integration of their action as P2X- and P2Y-receptor activating molecules. Mol Pharmacol 64(4):785–795
Lee HK, Shin YK, Jung J, Seo SY, Baek SY, Park HT (2009) Proteasome inhibition suppresses Schwann cell dedifferentiation in vitro and in vivo. Glia 57(16):1825–1834
Liu GJ, Bennett MR (2003) ATP secretion from nerve trunks and Schwann cells mediated by glutamate. NeuroReport 14(16):2079–2083
Liu GJ, Werry EL, Bennett MR (2005) Secretion of ATP from Schwann cells in response to uridine triphosphate. Eur J Neurosci 21(1):151–160
Martini R, Fischer S, López-Vales R, David S (2008) Interactions between Schwann cells and macrophages in injury and inherited demyelinating disease. Glia 56(14):1566–1577
Ralevic V, Burnstock G (1998) Receptors for purines and pyrimidines. Pharmacol Rev 50(3):413–492
Riches DW, Watkins JL, Stanworth DR (1983) Biochemical differences in the mechanism of macrophage lysosomal exocytosis initiated by zymosan particles and weak bases. Biochem J 212(3):869–874
Rodríguez A, Martinez I, Chung A, Berlot CH, Andrews NW (1999) cAMP regulates Ca2 + -dependent exocytosis of lysosomes and lysosome-mediated cell invasion by trypanosomes. J Biol Chem 274(24):16754–16759
Rotshenker S (2011) Wallerian degeneration: the innate-immune response to traumatic nerve injury. J Neuroinflammation 8:109
Shin YH, Lee SJ, Jung J (2012) Secretion of ATP from Schwann cells through lysosomal exocytosis during Wallerian degeneration. Biochem Biophys Res Commun 429(3–4):163–167
Shin YH, Lee SJ, Jung J (2013) Extracellular ATP inhibits Schwann cell dedifferentiation and proliferation in an ex vivo model of Wallerian degeneration. Biochem Biophys Res Commun 430(2):852–857
Stevens B, Fields RD (2000) Response of Schwann cells to action potentials in development. Science 287(5461):2267–2271
Takenouchi T, Nakai M, Iwamaru Y, Sugama S, Tsukimoto M, Fujita M, Wei J, Sekigawa A, Sato M, Kojima S, Kitani H, Hashimoto M (2009) The activation of P2X7 receptor impairs lysosomal functions and stimulates the release of autophagolysosomes in microglial cells. J Immunol 182(4):2051–2062
Tapper H, Sundler R (1995) Bafilomycin A1 inhibits lysosomal, phagosomal, and plasma membrane H(+)-ATPase and induces lysosomal enzyme secretion in macrophages. J Cell Physiol 163(1):137–144
Thomson CE, Griffiths IR, McCulloch MC, Kyriakides E, Barrie JA, Montague P (1993) In vitro studies of axonally-regulated Schwann cell genes during Wallerian degeneration. J Neurocytol 22(8):590–602
Webster HF (1965) The relationship between Schmidt-Lantermann incisures and myelin segmentation during Wallerian degeneration. Ann N Y Acad Sci 122:29–38
Zhang Z, Chen G, Zhou W, Song A, Xu T, Luo Q, Wang W, Gu XS, Duan S (2007) Regulated ATP release from astrocytes through lysosome exocytosis. Nat Cell Biol 9(8):945–953
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This work was supported by the Dong-A University research fund.
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Shin, Y.H., Chung, HJ., Park, C. et al. Adenosine 5′-Triphosphate (ATP) Inhibits Schwann Cell Demyelination During Wallerian Degeneration. Cell Mol Neurobiol 34, 361–368 (2014). https://doi.org/10.1007/s10571-013-0020-y
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DOI: https://doi.org/10.1007/s10571-013-0020-y