title: Neuroprotective effects of the beta-catenin stabilization in an oxygen- and glucose-deprived human neural progenitor cell culture system.
abstract: β-Catenin stabilization achieved either via GSK-3β specific inhibition or involving canonical Wnt signalling pathway, contributes to neuroprotection in an oxygen-glucose deprivation (4h OGD) in vitro hypoxia model performed on human cortical neural progenitor cells previously differentiated into neurons and glia. Neuroprotection mechanisms include both acquiring tolerance to injury throughout preconditioning (72 h prior to OGD) or being pro-survival during 24h reoxygenation after the insult. Four hours of OGD induced apoptotic cell death elevation to 73 ± 1% vs. 12% measured in control and the LDH level, indicative of necrotic cell injury, elevation by 67 ± 7% (set to 100%). A significant reduction in apoptosis occurred at 24h reoxygenation with indirubin supplement which was 49 ± 6% at 2.5 μM BIO while LDH level was only 47 ± 5% of OGD. Kenpaullone was efficient in reducing both cell deaths at 5 μM (apoptosis 38 ± 1% and necrosis 33 ± 3% less than in OGD). Wnt agonist reduced apoptosis to 45 ± 3% at 0.01 μM, while LDH value was decreased to a level of 53 ± 5% of control. Our findings suggest that GSK-3beta inhibitors/β-catenin stabilizers may ultimately be useful drugs in neuroprotection and neuroregeneration therapies in vivo.
authors.affiliation: Translational Centre for Regenerative Medicine, University of Leipzig, Philipp-Rosenthal-Straße 55, 04103 Leipzig, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Skardelly
authors.forename: Khaled
authors.initials: K
authors.lastname: Gaber
authors.forename: Johannes
authors.initials: J
authors.lastname: Schwarz
authors.forename: Javorina
authors.initials: J
authors.lastname: Milosevic
mesh_terms: D001552:Benzazepines / Q000494:pharmacology; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D001552:Benzazepines; D007211:Indoles; D018696:Neuroprotective Agents; D047428:Protein Kinase Inhibitors; D051176:beta Catenin; C119620:kenpaullone; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D005947:Glucose; D010100:Oxygen; C027185:indirubin