Autophagy protects against PI3K/Akt/mTOR-mediated apoptosis of spinal cord neurons after mechanical injury

Wang, Zhenyu; Zhou, Linlin; Zheng, Xiaoting; Chen, Gang; Pan, RongFeng; Li, JinHuang; Liu, Wenge

doi:10.1016/j.neulet.2017.07.036

Cited by 74 publications

(44 citation statements)

References 34 publications

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“…According to the literature, mTOR regulated the programmed cell death pathway of autophagy and apoptosis which can decide the development, differentiation, ageing, survival and ultimate fate of neuronal stem cells . In addition, it has been reported that AKT signalling pathway is involved in neuronal apoptosis and autophagy after mechanical injury . To explore whether the AKT/mTOR signalling pathway was involved in the process of muscone on autophagy and apoptosis of RSC 96 cells induced by HG, we assessed the expression of AKT, mTOR, phosphorylated AKT and phosphorylated mTOR after treating the RSC 96 cells with HG, HG + AKT/mTOR inhibitor, HG + Muscone or HG + Muscone + AKT/mTOR inhibitor.…”

Section: Resultsmentioning

confidence: 99%

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Muscone ameliorates diabetic peripheral neuropathy through activating AKT/mTOR signalling pathway

Dong

Bai

et al. 2019

Journal of Pharmacy and Pharmacology

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Objectives Emerging evidence showed that muscone could improve chronic inflammation after myocardial infarction and protect alcohol‐induced osteonecrosis of the femoral head. However, the function of muscone on diabetic peripheral neuropathy (DPN) is obscure. Methods The neuronal Schwann cell RSC 96 cells were treated with 125 mmol/l glucose to simulate the cells in DPN. The RSC 96 cell viability was detected by cell counting kit‐8. The RSC 96 cell cycle and apoptosis were determined by flow cytometry. The expression of marker proteins of apoptosis, autophagy and AKT/mTOR signalling pathway was assessed by Western blot. Key findings We observed that after high glucose (HG) treatment, the number of cell apoptosis was increased, cell proliferation was decreased, as well as the expression of apoptosis‐related proteins and autophagy‐related proteins were changed. However, this phenomenon can be reversed by muscone. Meanwhile, the expression of phosphorylated AKT and mammalian target of rapamycin (mTOR) was down‐regulated with HG treatment, while the expression quantity was up‐regulated after disposed with muscone. Conclusions Our outcomes demonstrated that autophagy and apoptosis of RSC 96 cells induced by HG can be alleviated by muscone through modulating AKT/mTOR signalling pathway, suggesting that muscone might be a potential molecule with influence in connection to DPN.

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Section: Resultsmentioning

confidence: 99%

“…As a major regulator of mammalian autophagy and apoptosis, mTOR is the central processor and integrator of internal and external signals . The occurrence of autophagy and apoptosis is accompanied by the inhibition of AKT/mTOR signalling pathway .…”

Section: Discussionmentioning

confidence: 99%

Muscone ameliorates diabetic peripheral neuropathy through activating AKT/mTOR signalling pathway

Dong

Bai

et al. 2019

Journal of Pharmacy and Pharmacology

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“…The PI3K/AKT signalling pathway plays pivotal roles in various cellular processes, including proliferation, differentiation, and apoptosis . In addition, the PI3K/AKT signalling pathway is also involved in the regulation of tumour progression.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐378‐3p/5p represses proliferation and induces apoptosis of oral squamous carcinoma cells via targeting KLK4

Cui

Bao

Liu

et al. 2020

Clin Exp Pharma Physio

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Oral squamous cell carcinoma (OSCC) is one of the most common types of head and neck neoplasm. Down‐regulation of hsa‐microRNA‐378 (miR‐378) has been proved in OSCC tissues, suggesting that miR‐378 might play crucial roles in the progression of OSCC. The present study aimed to evaluate the effect of miR‐378‐3p/5p on the proliferation and apoptosis of OSCC in vitro and in vivo. According to the results, lentivirus‐mediated overexpression of miR‐378 lowered the colony formation efficiency, blocked cell cycle progression, and decreased the percentage of Ki‐67 positive cells, whereas knockdown of miR‐378‐3p/5p led to the opposite results. Furthermore, the apoptosis of OSCC cells was induced by the overexpression of miR‐378 as evidenced by decreasing Bcl‐2/Bax ratio, increasing cleaved caspase‐9, cleaved caspase‐3, and cleaved PARP levels, and promoting the release of cytochrome c into the cytoplasm. However, the above results were reversed by miR‐378‐3p/5p silencing. In addition, the overexpression of miR‐378 inhibited the activation of PI3K/AKT signalling pathway. Conversely, miR‐378‐3p/5p knockdown resulted in the inactivation of PI3K/AKT signalling pathway. Mechanically, we validated that miR‐378‐3p/5p could target kallikrein‐related peptidase 4 (KLK4), and enforced overexpression of KLK4 counteracted miR‐378 overexpression‐induced apoptosis. Finally, tumourigenesis in nude mice was suppressed by the overexpression of miR‐378, which was promoted by miR‐378‐3p/5p silencing. Taken together, these results suggest that miR‐378 may be a potential target in the diagnoses and treatment of OSCC.

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“…functional defects in patients with SCI (26). Although the pathophysiological processes of SCI have been extensively studied, there are currently no effective treatments for patients with SCI (22). miRNAs are small, non-coding RNAs that suppress mRNA translation or induce mRNA degradation by binding to the 3'UTR of mRNA targets.…”

Section: Discussionmentioning

confidence: 99%

“…Subsequently, 2 ml neurobasal culture medium (Invitrogen; Thermo Fisher Scientific, Inc.) supplemented with glutamine, B27 and penicillin/streptomycin was added to the plates, and the neurons were grown in an incubator at 37˚C with 5% CO 2 . An SCI model in neurons was established by scratch according to previous study (22), and neurons without any treatment were used as the control group. At 24 h after scratching, neurons were harvested for subsequent analysis.…”

Section: Methodsmentioning

confidence: 99%

Protective role of microRNA‑219‑5p inhibitor against spinal cord injury via liver receptor homolog‑1/Wnt/β‑catenin signaling pathway regulation

Shen

2018

Exp Ther Med

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Abstract. The present study aimed to investigate the role of microRNA (miR)-219-5p in spinal cord injury (SCI) and to examine the underlying molecular mechanism. SCI rat and cell models were conducted in the current study, while reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the level of miR-219-5p in the SCI mice and neurons. Bioinformatics analysis was applied to predict the target genes of miR-219-5p, and dual-luciferase reporter assay was performed to verify the prediction. In addition, MTT assay and flow cytometry were conducted to determine the cell viability and cell apoptosis of the neurons, respectively. Western blot analysis was also performed to detect the expression of associated proteins. The study results demonstrated that miR-219-5p was highly expressed in SCI mice and neurons, and directly targets liver receptor homolog-1 (LRH-1). The neuron viability was significantly reduced by SCI, however, it was recovered upon transfection with an miR-219-5p inhibitor. Neuron apoptosis was notably induced by SCI and inhibited by miR-219-5p inhibition. The LRH-1/Wnt/β-catenin signaling pathway was also inhibited by SCI, while it was significantly enhanced by the miR-219-5p inhibitor. Furthermore, LRH-1 overexpression eliminated the effects of the miR-219-5p inhibitor on SCI. In conclusion, these data indicated that the miR-219-5p inhibitor served a protective role in SCI via regulating the LRH-1/Wnt/β-catenin signaling pathway.

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Autophagy protects against PI3K/Akt/mTOR-mediated apoptosis of spinal cord neurons after mechanical injury

Cited by 74 publications

References 34 publications

Muscone ameliorates diabetic peripheral neuropathy through activating AKT/mTOR signalling pathway

Muscone ameliorates diabetic peripheral neuropathy through activating AKT/mTOR signalling pathway

MicroRNA‐378‐3p/5p represses proliferation and induces apoptosis of oral squamous carcinoma cells via targeting KLK4

Protective role of microRNA‑219‑5p inhibitor against spinal cord injury via liver receptor homolog‑1/Wnt/β‑catenin signaling pathway regulation

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