title: Negletein as a neuroprotectant enhances the action of nerve growth factor and induces neurite outgrowth in PC12 cells.
abstract: Negletein has been shown to have therapeutic potential for inflammation-associated diseases, but its effect on neurite outgrowth is still unknown. The present study showed that negletein alone did not trigger PC12 cells to differentiate and extend neurites. When compared with the cells in the untreated control, a significant (P < 0.05) induction and a higher neurite outgrowth activity was observed when the cells were cotreated with negletein (10 µM) and a low dose of nerve growth factor (NGF; 5 ng/mL). The neurite outgrowth process was blocked by the tyrosine kinase receptor (Trk) inhibitor, K252a, suggesting that the neuritogenic effect was NGF-dependent. Negletein (10 µM) together with NGF (5 ng/mL) enhanced the phosphorylation of extracellular signal-regulated kinases (ERKs), protein kinase B (Akt), and cAMP response element-binding protein (CREB). The growth associated protein-43 (GAP-43) and the NGF level were also upregulated by negletein (10 µM) and a low dose of NGF (5 ng/mL). Negletein at nanomolar concentration also was found to be sufficient to mediate the survival of serum-deprived PC12 cells up to 72 h. Taken together, negletein might be useful as an efficient bioactive compound to protect neurons from cell death and promote neuritogenesis. © 2016 BioFactors, 42(6):591-599, 2016.
authors.affiliation: Mushroom Research Centre, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, 50603, Malaysia.|Centre of Excellence for Learning and Teaching (CELT), UCSI University, No. 1, Jalan Menara Gading, UCSI Heights, Cheras, Kuala Lumpur, 56000, Malaysia.
authors.forename: Chia-Wei
authors.identifier: http://orcid.org/0000-0003-1373-1374
authors.initials: CW
authors.lastname: Phan
authors.affiliation: Mushroom Research Centre, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, 50603, Malaysia.|Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, 50603, Malaysia.
authors.forename: Vikineswary
authors.initials: V
authors.lastname: Sabaratnam
authors.affiliation: C.N.R. IBPM, Department of Chemistry, Sapienza University of Rome, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bovicelli
authors.affiliation: C.N.R. IBPM, Department of Chemistry, Sapienza University of Rome, Rome, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Righi
authors.affiliation: Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, Rome, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Saso
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D047309:Flavones / Q000494:pharmacology*; D019922:GAP-43 Protein / Q000378:metabolism; D020935:MAP Kinase Signaling System; D020932:Nerve Growth Factor / Q000494:pharmacology / Q000502:physiology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D000071446:Neuronal Outgrowth / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D047309:Flavones; D019922:GAP-43 Protein; C502240:NGF protein, human; D018696:Neuroprotective Agents; C507557:negletein; D020932:Nerve Growth Factor; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: NGF; PC12; flavonoid; negletein; neurite outgrowth; neuroprotection