Premium
Astroglia up‐regulate transcription and secretion of ‘readthrough’ acetylcholinesterase following oxidative stress
Author(s) -
Bond C. E.,
Patel P.,
Crouch L.,
Tetlow N.,
Day T.,
AbuHayyeh S.,
Williamson C.,
Greenfield S. A.
Publication year - 2006
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2006.04898.x
Subject(s) - acetylcholinesterase , oxidative stress , aché , neurodegeneration , secretion , microbiology and biotechnology , extracellular , chemistry , biology , biochemistry , medicine , enzyme , disease
Novel and diverse functions of glial cells are currently the focus of much attention [A. Volterra and J. Meldolesi (2005) Nature Rev . 6, 626–640]. Here we present evidence that rat astroglia release acetylcholinesterase (AChE) as part of their response to hypoxic damage. Exposure of astroglia to tert‐butyl hydroperoxide, and hence oxidative stress, subsequently leads to a switching in mRNA from the classical membrane‐bound T‐AChE to a preferential increase in the splice variant for a soluble form, R‐AChE, This change in expression is reflected in increased perinuclear and reduced cytoplasmic AChE staining of the insulted glial cells, with a concomitant and marked increase in extracellular secretion that peaks at 1 h post‐treatment. An analogous increase in R‐AChE, over a similar time scale, occurs in response to psychological stress [D. Kaufer et al . (1998) Nature 93, 373–377], as well as to head injury and stroke [E. Shohami et al . (1999) J. Neurotrauma 6, 365–76]. The data presented here suggest that glial cells may be key chemical intermediaries in such situations and, perhaps more generally in pathological conditions involving oxidative stress, such as neurodegeneration.