Gene interactions and pathways from curated databases and text-mining
PloS one 2013, PMID: 23904909

Cell type-specific dependency on the PI3K/Akt signaling pathway for the endogenous Epo and VEGF induction by baicalein in neurons versus astrocytes.

Sun, Yu-Yo; Lin, Shang-Hsuan; Lin, Hung-Cheng; Hung, Chia-Chi; Wang, Chen-Yu; Lin, Yen-Chu; Hung, Kuo-Sheng; Lien, Cheng-Chang; Kuan, Chia-Yi; Lee, Yi-Hsuan

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.

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Text Mining Data

VEGF — PI3K/Akt: " Our results show that baicalein induced Epo and VEGF expression in a HIF1a- and PI3K/Akt dependent manner in neurons "

VEGF — PI3K/Akt: " Our results show that baicalein induced Epo and VEGF expression in a HIF1a- and PI3K/Akt dependent manner in neurons "

Epo — PI3K/Akt: " Our results show that baicalein induced Epo and VEGF expression in a HIF1a- and PI3K/Akt dependent manner in neurons "

Epo — PI3K/Akt: " Our results show that baicalein induced Epo and VEGF expression in a HIF1a- and PI3K/Akt dependent manner in neurons "

VEGF → HIF1a: " Moreover, only baicalein induced astrocytic VEGF , but not Epo expression requires HIF1a , while PI3K/Akt signaling had little role in baicalein induced astrocytic Epo/VEGF expression "

HIF1a → Epo: " Moreover, only baicalein induced astrocytic VEGF, but not Epo expression requires HIF1a , while PI3K/Akt signaling had little role in baicalein induced astrocytic Epo/VEGF expression "

Manually curated Databases

No curated data.