Library Open Repository

Redefining the role of metallothionein within the injured brain: extracellular metallothioneins play an important role in the astrocyte-neuron response to injury

Downloads

Downloads per month over past year

Chung, RS and Penkowa, M and Dittman, J and King, CE and Bartlett, C and Asmussen, JW and Hidalgo, J and Carrasco, J and Leung, YK and Walker, AK and Fung, SJ and Dunlop, SA and Fitzgerald, M and Beazley, LD and Chuah, MI and Vickers, JC and West, AK (2008) Redefining the role of metallothionein within the injured brain: extracellular metallothioneins play an important role in the astrocyte-neuron response to injury. Journal of Biological Chemistry, 283 (22). pp. 15349-15358. ISSN 0021-9258

[img] PDF
Chung_J_Biol_Chem.pdf | Request a copy
Full text restricted
Available under University of Tasmania Standard License.

Abstract

Anumber of intracellular proteins that are protective after brain injury are classically thought to exert their effect within the expressing cell. The astrocytic metallothioneins (MT) are one example and are thought to act via intracellular free radical scavenging and heavy metal regulation, and in particular zinc. Indeed, wehave previously established that astrocyticMTsare required for successful brain healing. Here we provide evidence for a fundamentally different mode of action relying upon intercellular transfer from astrocytes to neurons, which in turn leads to uptake-dependent axonal regeneration. First, we show that MT can be detected within the extracellular fluid of the injured brain, and that cultured astrocytes are capable of actively secreting MT in a regulatable manner. Second,weidentify a receptor, megalin, that mediatesMTtransportintoneurons. Third,wedirectlydemonstratefor the first time the transfer ofMTfrom astrocytes to neurons over a specific time course in vitro. Finally, we show that MT is rapidly internalizedviathecellbodiesofretinalganglioncellsinvivoandis a powerful promoter of axonal regeneration through the inhibitory environment of the completely severed mature optic nerve. Our work suggests that the protective functions of MT in the central nervoussystemshouldbewidenedfromapurelyastrocyticfocusto include extracellular and intra-neuronal roles. This unsuspected action of MT represents a novel paradigm of astrocyte-neuronal interaction after injury and may have implications

Item Type: Article
Journal or Publication Title: Journal of Biological Chemistry
Page Range: pp. 15349-15358
ISSN: 0021-9258
Identification Number - DOI: 10.1074/jbc.M708446200
Additional Information: Copyright © 2008 by the American Society for Biochemistry and Molecular Biology.
Date Deposited: 02 Jul 2008 22:31
Last Modified: 18 Nov 2014 03:44
URI: http://eprints.utas.edu.au/id/eprint/6914
Item Statistics: View statistics for this item

Repository Staff Only (login required)

Item Control Page Item Control Page