Cell type-specific dependency on the PI3K/Akt signaling pathway for the endogenous Epo and VEGF induction by baicalein in neurons versus astrocytes
| Autor: | Yi Hsuan Lee, Hung Cheng Lin, Chia-Yi Kuan, Cheng Chang Lien, Yu-Yo Sun, Kuo Sheng Hung, Chia Chi Hung, Chen Yu Wang, Shang Hsuan Lin, Yen-Chu Lin |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Transcriptional Activation Vascular Endothelial Growth Factor A lcsh:Medicine Biology Neuroprotection Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound Phosphatidylinositol 3-Kinases 0302 clinical medicine Animals Enzyme Inhibitors lcsh:Science Protein kinase B Erythropoietin PI3K/AKT/mTOR pathway Cells Cultured 030304 developmental biology Neurons 0303 health sciences Multidisciplinary Akt/PKB signaling pathway lcsh:R Hypoxia-Inducible Factor 1 alpha Subunit Cell biology Baicalein Rats Vascular endothelial growth factor Vascular endothelial growth factor A Neuroprotective Agents chemistry Astrocytes Immunology Flavanones Female lcsh:Q Signal transduction Proto-Oncogene Proteins c-akt 030217 neurology & neurosurgery Signal Transduction Research Article |
| Zdroj: | PLoS ONE, Vol 8, Iss 7, p e69019 (2013) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | The neuroprotective effect of baicalein is generally attributed to inhibition of 12/15-lipoxygenase (12/15-LOX) and suppression of oxidative stress, but recent studies showed that baicalein also activates hypoxia-inducible factor-α (HIF1α) through inhibition of prolyl hydrolase 2 (PHD2) and activation of the phosphatidylinositide-3 kinase (PI3K)/Akt signaling pathway. Yet, the significance and regulation of prosurvival cytokines erythropoietin (Epo) and vascular endothelial growth factor (VEGF), two transcriptional targets of HIF1α, in baicalein-mediated neuroprotection in neurons and astrocytes remains unknown. Here we investigated the causal relationship between the PI3K/Akt signaling pathway and Epo/VEGF expression in baicalein-mediated neuroprotection in primary rat cortical neurons and astrocytes. Our results show that baicalein induced Epo and VEGF expression in a HIF1α- and PI3K/Akt-dependent manner in neurons. Baicalein also protected neurons against excitotoxicity in a PI3K- and Epo/VEGF-dependent manner without affecting neuronal excitability. In contrast, at least a 10-fold higher concentration of baicalein was needed to induce Epo/VEGF production and PI3K/Akt activity in astrocytes for protection of neurons. Moreover, only baicalein-induced astrocytic VEGF, but not Epo expression requires HIF1α, while PI3K/Akt signaling had little role in baicalein-induced astrocytic Epo/VEGF expression. These results suggest distinct mechanisms of baicalein-mediated Epo/VEGF production in neurons and astrocytes for neuroprotection, and provide new insights into the mechanisms and potential of baicalein in treating brain injury in vivo. |
| Databáze: | OpenAIRE |
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