NDLI: Calpain-Dependent ErbB4 Cleavage Is Involved in Brain Ischemia-Induced Neuronal Death

Content Provider	Springer Nature Link
Author	Lu, Ying mei Gao, Yin ping Tao, Rong rong Liao, Mei hua Huang, Ji yun Wu, Gang Han, Feng Li, Xiao ming
Copyright Year	2015
Abstract	Disturbance of neuregulin-1β/ErbB4 signaling is considered to be associated with brain ischemia, but the mechanisms of this disruption are largely unknown. In the present study, we provide evidence that degradation of ErbB4 is involved in neuronal cell death in response to ischemia. Our data showed that the application of neuregulin-1β provided significant protection against oxygen–glucose deprivation (OGD)-induced neuronal death as detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, annexin V/propidium iodide flow cytometry analysis and terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL) staining. Furthermore, neuregulin-1β treatment significantly reduced the infarct volume of ischemic mice, and this result was not seen in the ErbB4 knockout mice. We found that brain ischemia induced the breakdown of ErbB4 in a time-dependent manner in vivo, but not that of ErbB2. In vitro studies further indicated that recombinant calpain induced the cleavage of ErbB4 in a dose-dependent way, whereas the calpain inhibitor significantly reduced the OGD-induced ErbB4 breakdown. Additionally, OGD-induced apoptosis was partially abolished by transfection with the ErbB4$_{E872K}$ mutant. Taken together, neuregulin-1β elicits its neuroprotective effect in an ErbB4-dependent manner, and the cleavage of ErbB4 by calpain contributes to a neuronal cell death cascade during brain ischemia.
Starting Page	2600
Ending Page	2609
Page Count	10
File Format	PDF
ISSN	08937648
Journal	Molecular Neurobiology
Volume Number	53
Issue Number	4
e-ISSN	15591182
Language	English
Publisher	Springer US
Publisher Date	2015-06-21
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Brain ischemia ErbB4 Calpain Cleavage Neuregulin-1β Neurosciences Neurobiology Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Neurology Cellular and Molecular Neuroscience

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