Senkyunolide H protects PC12 cells from OGD/R-induced injury via cAMP-PI3K/AKT signaling pathway

Background: MicroRNA-133b (miR-133b) has been shown to play a critical role in spinal cord regeneration. The aim of this study was to investigate the cellular role of miR-133b in neural cells. Methods: PC12 cells and primary cortical neurons (PCNs) were transfected with lenti-miR-133b, lenti-miR-133b inhibitor, plasmid-shRNA-RhoA, plasmid-RhoA and their negative controls. After 48 hours of transfection, the levels of proteins and mRNA or miRNA were evaluated by Western blotting and qRT-PCR, respectively. Moreover, the neurite outgrowth was analyzed by Image J. For pharmacological experiments, inhibitors of MEK1/2 kinase (PD98059), phosphoinositide-3 kinase (PI3K) (LY294002) and ROCK (Y27632) were added into the culture medium. Results: Overexpression of miR-133b in PC12 cells enhanced neurite outgrowth. Conversely, inhibition of miR-133b reduced neurite length. We further identified RhoA as a target and mediator of mir-133b for neurite extension by Western blot and knockdown experiment. Moreover, overexpression of RhoA could attenuate the neurite growth effects of miR-133b. Also, we observed that miR-133b activated MEK/ERK and PI3K/Akt signaling pathway by targeting RhoA. Finally, in PCNs, miR-133b also increased axon growth and attenuated axon growth restrictions from chondroitin sulfate proteoglycans (CSPG). Conclusions: In summary, our study suggested that miR-133b regulated neurite outgrowth via ERK1/2 and PI3K/Akt signaling pathway by RhoA suppression.

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Grape seed proanthocyanidins protect PC12 cells from hydrogen peroxide-induced damage via the PI3K/AKT signaling pathway

Neuroscience Letters ◽

10.1016/j.neulet.2021.135793 ◽

2021 ◽

Vol 750 ◽

pp. 135793

Author(s):

Xuegang He ◽

Xudong Guo ◽

Zhanjun Ma ◽

Ying Li ◽

Jihe Kang ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Signaling Pathway ◽

Pc12 Cells ◽

Grape Seed ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Grape Seed Proanthocyanidins

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Resveratrol against 6-OHDA-induced damage of PC12 cells via PI3K/Akt

Translational Neuroscience ◽

10.1515/tnsci-2020-0165 ◽

2021 ◽

Vol 12 (1) ◽

pp. 138-144

Author(s):

Nanqu Huang ◽

Juan Huang ◽

Ying Zhang ◽

Mingji Chen ◽

Jingshan Shi ◽

...

Keyword(s):

Protective Effect ◽

Cell Viability ◽

Signaling Pathway ◽

Pc12 Cells ◽

Akt Signaling ◽

Leakage Rate ◽

Motor Dysfunction ◽

Akt Signaling Pathway ◽

Sod Activity

Abstract Objective Our previous in vivo study found that resveratrol (Res), which is a phytoalexin, attenuated 6-hydroxydopamine (6-OHDA)-induced motor dysfunction by activating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway in rats. Therefore, we further explored the protective effect of Res on 6-OHDA-induced damage to PC12 cells in vitro with respect to the PI3K/Akt signaling pathway. Methods We incubated PC12 cells with 75 μM 6-OHDA for 24 h, and Res was then added at a final concentration of 25 μM; the protective effect was examined via MTT and lactate dehydrogenase (LDH) assays. In addition, the PI3K inhibitor LY294002 was used to investigate the potential mechanism. JC-1 staining was used to detect the mitochondrial membrane potential (MMP), and western blotting (WB) was used to detect the phosphorylation of Akt-Ser473. Results Compared with that in the control, the cell viability, total superoxide dismutase (SOD) activity, MMP, and p-Akt-Ser473 level of 6-OHDA-treated PC12 cells were significantly decreased, while the leakage rate of LDH was increased. And after treatment with 25 μM Res, the cell viability, total SOD activity, MMP, and p-Akt-Ser473 level of 6-OHDA-treated PC12 cells were significantly increased compared with those of the control cells, while the leakage rate of LDH was decreased. These effects of Res were antagonized by LY294002. Conclusions Res ameliorates 6-OHDA-induced damage to PC12 cells via activation of the PI3K/Akt signaling pathway.

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