title: Astroglia up-regulate transcription and secretion of 'readthrough' acetylcholinesterase following oxidative stress.
abstract: 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.
authors.affiliation: University Department of Pharmacology, Mansfield Road, Oxford OX1 3QT, UK. cherie.bond@pharm.ox.ac.uk
authors.forename: C E
authors.initials: CE
authors.lastname: Bond
authors.forename: P
authors.initials: P
authors.lastname: Patel
authors.forename: L
authors.initials: L
authors.lastname: Crouch
authors.forename: N
authors.initials: N
authors.lastname: Tetlow
authors.forename: T
authors.initials: T
authors.lastname: Day
authors.forename: S
authors.initials: S
authors.lastname: Abu-Hayyeh
authors.forename: C
authors.initials: C
authors.lastname: Williamson
authors.forename: S A
authors.initials: SA
authors.lastname: Greenfield
mesh_terms: D000109:Acetylcholine / Q000096:biosynthesis; D000110:Acetylcholinesterase / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D017398:Alternative Splicing / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002478:Cells, Cultured; D002534:Hypoxia, Brain / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D012269:Ribosomal Proteins / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012995:Solubility; D015533:Transcriptional Activation; D015854:Up-Regulation / Q000502:physiology; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
chemical_list: D020033:Protein Isoforms; D012333:RNA, Messenger; D012269:Ribosomal Proteins; D020122:tert-Butylhydroperoxide; D000110:Acetylcholinesterase; D000109:Acetylcholine