p53 inhibition provides a pivotal protective effect against ischemia-reperfusion injury in vitro via mTOR signaling

Li, Xiaomu; Gu, Shaohua; Ling, Yan; Shen, Chao; Cao, Xiaoyun; Xie, Rong

doi:10.1016/j.brainres.2015.02.009

Cited by 20 publications

(15 citation statements)

References 27 publications

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“…Hereby, a mechanism connecting ischemic stroke and MDM2 has been confirmed. Previous studies have confirmed our findings that p53 inhibition has a key protective effect against ischemia-reperfusion injury in vitro and provides a promising therapeutic target against stroke [31,32].…”

Section: Discussionsupporting

confidence: 88%

MALAT1 Activates the P53 Signaling Pathway by Regulating MDM2 to Promote Ischemic Stroke

Zhang

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: This study focused on evaluating the effect of MALAT1 and MDM2 on ischemic stroke through regulation of the p53 signaling pathway. Materials: Bioinformatics analysis was performed to identify abnormally expressed lncRNAs, mRNAs and their associated pathways. Oxygen-glucose deprivation/reoxygenation (OGD/R) in cells and middle cerebral artery occlusion/reperfusion (MCAO/R) in mice were performed to simulate an ischemic stroke environment. Western blot and qRT-PCR were used to examine lncRNA expression and mRNA levels. Fluorescence in situ hybridization (FISH) LncRNA was used to locate mRNA. MTT and flow cytometry were performed to examine cell proliferation and apoptosis. Finally, immunohistochemistry was used to observe the expression of genes in vivo. Results: MALAT1 and MDM2, which exhibit strong expression in stroke tissues, were subjected to bioinformatics analysis, and the p53 pathway was chosen for further study. MALAT1, MDM2 and p53 signaling pathway-related proteins were all up regulated in OGD/R cells. Furthermore, Malat1, Mdm2 and p53 pathway related-proteins were also up regulated in MCAO/R mice. Both MALAT1 and MDM2 were localized in the nuclei. Down regulation of MALAT1 and MDM2 enhanced cell proliferation ability and reduced apoptosis, resulting in decreased infarct size in MCAO/R brains. Conclusion: These results indicate that MALAT1/MDM2/p53 signaling pathway axis may provide more effective clinical therapeutic strategy for patients with ischemic stroke.

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Section: Discussionsupporting

confidence: 88%

MALAT1 Activates the P53 Signaling Pathway by Regulating MDM2 to Promote Ischemic Stroke

Zhang

Wang

et al. 2018

Cell Physiol Biochem

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“…14 Besides, p53 inhibition has been demonstrated to exert pivotal protection against IRI. 15 Thus, based on the review of the current existing literature, we subsequently asserted the hypothesis that silencing miR-23b could protect against IRI through the inhibition of the p53 signaling pathway by targeting MDM4. Hence, the current study was designed to explore the regulatory mechanisms of the miR-23b/MDM4/p53 signaling pathway in IRI and its effect on the apoptosis of articular chondrocytes.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Downregulation of microRNA‐23b protects against ischemia‐reperfusion injury via p53 signaling pathway by upregulating MDM4 in rats

Zhao

Guan

et al. 2018

J of Cellular Biochemistry

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Total knee arthroplasty is a commonly performed safe procedure and typically executed in severe knee arthritis, but it also triggers ischemia-reperfusion injury (IRI). More recently, microRNAs (miRs) have been reported to play a contributory role in IRI through the key signaling pathway. Hence, the current study aimed to investigate the effect and specific mechanism of microRNA-23b (miR-23b), murine double minute 4 (MDM4), and the p53 signaling pathway in IRI rat models. First, the IRI model was established, and the expression pattern of miR-23b, MDM4, and the p53 signaling pathway-related genes was characterized in cartilaginous tissues. Then, miR-23b mimics or inhibitors were applied for the elevation or the depletion of the miR-23b expression and siRNA-MDM4 for the depletion of the MDM4 expression in the articular chondrocytes. By means of immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blot analysis, IRI rats exhibited increased miR-23b expression, activated p53 signaling pathway, and decreased MDM4 expression. MDM4 was verified as a target gene of miR-23b through. Downregulated miR-23b increased the expression of MDM4, AKT, and Bcl-2, but decreased the expression of p53, p21, and Bax. In addition, a series of cell experiments demonstrated that downregulated miR-23b promoted articular chondrocyte proliferation and cell cycle entry, but inhibited articular chondrocyte apoptosis. The absence of the effects of miR-23b was observed after MDM4 knocked down. Our results indicate that silencing miR-23b could act to attenuate IRI and reduce the apoptosis of articular chondrocytes through inactivation of the p53 signaling pathway by upregulating MDM4, which provide basic therapeutic considerations for a novel target against IRI. K E Y W O R D S articular chondrocytes, ischemia-reperfusion injury (IRI), murine double minute 4 (MDM4), microRNA-23b (miR-23b), p53 signaling pathway J Cell Biochem. 2019;120:4599-4612.wileyonlinelibrary.com/journal/jcb

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“…P53, as a transcription factor, is critical for activation or suppression of multiple genes 5 . In addition to its established effects on tumor 6 , metabolism 7 and cell cycle 8 , p53 has also been reported to be up-regulated in cerebral ischemia 9 10 . The induced p53 potentiated impairment resulting from cerebral ischemia 11 12 .…”

mentioning

confidence: 99%

Regenerative repair of Pifithrin-α in cerebral ischemia via VEGF dependent manner

Zhang

Lei

Sun

et al. 2016

Sci Rep

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Promoting regenerative repair, including neurogenesis and angiogenesis, may provide a new therapeutic strategy for treatment of stroke. P53, a well-documented transcription factor, has been reported to be involved in cerebral ischemia and also serves as an important regulator of vascular endothelial growth factor (VEGF). However, the role of p53 in endogenous regenerative repair after brain ischemia is poorly understood. In this study, we investigated the effects of PFT-α, a specific p53 inhibitor on neurogenesis and angiogenesis improvement and associated signal pathways in rats impaired by cerebral artery occlusion (MCAo). PFT-α induced neuroprotection, reduced infarct volume and neurological functional impairment after ischemic stroke. More importantly, neurogenesis and angiogenesis were greatly enhanced by PFT-α, and accompanied by increased expression of VEGF. Moreover, we got consistent results in neural stem cells (NSCs) isolated from fetal rats. In contrast, application of the anti-VEGF neutralizing antibody (RB-222) partially reversed PFT-α-induced neuroprotection and rescued p53 expression. Noteworthily, inhibition of p53 after ischemic stroke in these rats improved their outcomes via promotion of regenerative repair. In conclusion, PFT-α could serve as a promising therapeutic strategy for ischemic stroke by promoting regenerative repair.

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p53 inhibition provides a pivotal protective effect against ischemia-reperfusion injury in vitro via mTOR signaling

Cited by 20 publications

References 27 publications

MALAT1 Activates the P53 Signaling Pathway by Regulating MDM2 to Promote Ischemic Stroke

MALAT1 Activates the P53 Signaling Pathway by Regulating MDM2 to Promote Ischemic Stroke

RETRACTED: Downregulation of microRNA‐23b protects against ischemia‐reperfusion injury via p53 signaling pathway by upregulating MDM4 in rats

Regenerative repair of Pifithrin-α in cerebral ischemia via VEGF dependent manner

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