Robust Neuritogenesis‐Promoting Activity by Bis(heptyl)‐Cognitin Through the Activation of alpha7‐Nicotinic Acetylcholine Receptor/ERK Pathway
| Autor: | Karl Wah Keung Tsim, Yuanjia Hu, Wei Cui, Chung Lit Choi, Sheng Quan Hu, Yuan Ping Pang, Yifan Han, Gang Li, Shing Hung Mak |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
MAPK/ERK pathway
Atropine Neurite alpha7 Nicotinic Acetylcholine Receptor MAP Kinase Signaling System p38 mitogen-activated protein kinases Green Fluorescent Proteins Alpha7 Nicotinic Acetylcholine Receptor Carbazoles Cholinergic Agents Oligonucleotides Biology Indole Alkaloids Small hairpin RNA Rats Sprague-Dawley Downregulation and upregulation Western blot Physiology (medical) Nerve Growth Factor medicine Neurites Animals Pharmacology (medical) Enzyme Inhibitors Cells Cultured Acetylcholine receptor Pharmacology Cerebral Cortex Neurons Amyloid beta-Peptides medicine.diagnostic_test Cell Differentiation Original Articles Molecular biology Peptide Fragments Triterpenes Rats Psychiatry and Mental health nervous system Animals Newborn |
| Popis: | Summary Aims Neurodegenerative disorders are caused by progressive neuronal loss in the brain, and hence, compounds that could promote neuritogenesis may have therapeutic values. In this study, the effects of bis(heptyl)-cognitin (B7C), a multifunctional dimer, on neurite outgrowth were investigated in both PC12 cells and primary cortical neurons. Methods Immunocytochemical staining was used to evaluate the proneuritogenesis effects, and Western blot and short hairpin RNA assays were applied to explore the underlying mechanisms. Results B7C (0.1–0.5 μM) induced robust neurite outgrowth in PC12 cells, as evidenced by the neurite-bearing morphology and upregulation of growth-associated protein-43 expression. In addition, B7C markedly promoted neurite outgrowth in primary cortical neurons as shown by the increase in the length of β-III-tubulin-positive neurites. Furthermore, B7C rapidly increased ERK phosphorylation. Specific inhibitors of alpha7-nicotinic acetylcholine receptor (α7-nAChR) and MEK, but not those of p38 or JNK, blocked the neurite outgrowth as well as ERK phosphorylation induced by B7C. Most importantly, genetic depletion of α7-nAChR significantly abolished B7C-induced neurite outgrowth in PC12 cells. Conclusion B7C promoted neurite outgrowth through the activation of α7-nAChR/ERK pathway, which offers novel insight into the potential application of B7C in the treatment of neurodegenerative disorders. |
| Databáze: | OpenAIRE |
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