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Cerebrolysin protects PC12 cells from CoCl 2 ‐induced hypoxia employing GSK3β signaling
Author(s) -
Hartwig Kerstin,
Fackler Viktoria,
JakschBogensperger Heidi,
Winter Stefan,
Furtner Tanja,
CouillardDespres Sebastien,
Meier Dieter,
Moessler Herbert,
Aigner Ludwig
Publication year - 2014
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2014.07.005
Subject(s) - cerebrolysin , neuroprotection , pharmacology , chemistry , cytotoxicity , apoptosis , biochemistry , medicine , in vitro
Cerebrolysin (EVER Neuro Pharma GmbH, Austria) is a peptidergic drug indicated for clinical use in stroke, traumatic brain injury and dementia. The therapeutic effect of Cerebrolysin is thought to ensure from its neurotrophic activity, which shares some properties with naturally occurring neurotrophic factors. However, the exact mechanism of action of Cerebrolysin is yet to be fully deciphered. This study aimed to investigate the neuroprotective effect of Cerebrolysin in a widely used in vitro model of hypoxia‐induced neuronal cytotoxicity, namely cobalt chloride (CoCl 2 )‐treatment of PC12 cells. CoCl 2 ‐cytotoxicity was indicated by a reduced cell‐diameter, cell shrinkage, increased pro‐apoptotic Caspase‐activities and a decreased metabolic activity. Cerebrolysin maintained the cell‐diameter of CoCl 2 ‐treated naïve PC12 cells, decreased the activation of Caspase 3/7 in CoCl 2 ‐stressed naïve PC12 cells and restored the cells' metabolic activity in CoCl 2 ‐impaired naïve and differentiated PC12 cells. Cerebrolysin treatment also decreased the levels of superoxide observed after exposure to CoCl 2 . Investigating the mechanism of action, we could demonstrate that Cerebrolysin application to CoCl 2 ‐stressed PC12 cells increased the phosphorylation of GSK3β, resulting in the inhibition of GSK3β. This might become clinically relevant for Alzheimer's disease, since GSK3β activity has been linked to the production of amyloid beta. Taken together, Cerebrolysin was found to have neuroprotective effects in CoCl 2 ‐induced cytotoxicity in PC12 cells.