Aldolase C/zebrin II is released to the extracellular space after stroke and inhibits the network activity of cortical neurons.
Cell death after stroke involves apoptotic, autophagocytic and necrotic mechanisms which may cause the release of cytosolic proteins to the extracellular space. Aldolase C (AldC) is the brain specific isoform of the glycolytic enzyme fructose-1,6-bisphosphate aldolase. According to its characteristic striped expression pattern in the adult cerebellum AldC is also termed zebrin II. Here, we demonstrate release of AldC into the cerebrospinal fluid (CSF) after stroke in vivo. Studies with cell cultures confirmed that AldC is released to the extracellular space after hypoxia. Moreover, addition of purified recombinant AldC to networks of cortical neurons plated on multielectrode arrays reversibly inhibited the spontaneous generation of action potentials at AldC concentrations which can be expected to occur after lesions of the human cerebral cortex. This mechanism could be relevant in the pathogenesis of the electrophysiological changes in the penumbra region after stroke.
Linke
Stephanie
S
Institut für Physiologische Chemie, Rheinische Friedrich-Wilhelms-Universität Bonn, Nussallee 11, D-53115, Bonn, Germany.
Goertz
Philipp
P
Baader
Stephan L
SL
Gieselmann
Volkmar
V
Siebler
Mario
M
Junghans
Ulrich
U
Kappler
Joachim
J
D000328:Adult; D000818:Animals; D001037:Aphasia / Q000209:etiology; D015153:Blotting, Western; D016923:Cell Death; D045744:Cell Line, Tumor; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D002544:Cerebral Infarction / Q000150:complications / Q000209:etiology; D003001:Cloning, Molecular; D004591:Electrophoresis, Polyacrylamide Gel; D004594:Electrophysiology; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism*; D005260:Female; D006429:Hemiplegia / Q000209:etiology; D006801:Humans; D007700:Kinetics; D008297:Male; D009072:Moyamoya Disease / Q000150:complications / Q000473:pathology; D009415:Nerve Net / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000134:cerebrospinal fluid* / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D010957:Plasmids / Q000235:genetics; D051381:Rats; D020521:Stroke / Q000134:cerebrospinal fluid* / Q000378:metabolism / Q000503:physiopathology*
D009419:Nerve Tissue Proteins; C071871:zebrin II