Cyclophilin A inhibits A549 cell oxidative stress and apoptosis by modulating the PI3K/Akt/mTOR signaling pathway

Ma, Zhenling; Zhang, Wenwen; Wu, Yaru; Zhang, Menghao; Wang, Lei; Wang, Yihan; Wang, Yi; Liu, Wei

doi:10.1042/bsr20203219

Cited by 29 publications

(14 citation statements)

References 57 publications

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“…The production of ROS and MDA and the changes in SOD activity are important markers of oxidative stress in cells [ 12 ]. Previous studies have shown that ROS is an important mediator of H 2 O 2 -induced cell death [ 13 ].…”

Section: Resultsmentioning

confidence: 99%

Protein Kinase N2 Reduces Hydrogen Peroxide-inducedDamage and Apoptosis in PC12 Cells by AntiOxidative Stress and Activation of the mTOR Pathway

Wang

Zhang

2022

Evidence-Based Complementary and Alternative Medicine

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Objective. To investigate the role and mechanism of protein kinase N2 (PKN2) in hydrogen peroxide (H2O2)-induced injury of PC12 cells. Methods. PC12 cells were transfected with lentivirus to knock down or overexpress PKN2 and then were treated with 300 μM H2O2 to establish a cell model of oxidative stress injury. The cell viability of PC12 cells in each group was determined by the CCK-8 method. Biochemical assays were used to measure reactive oxygen species (ROS), malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activity. Western blot was used to detect the protein expressions of PKN2, caspase-3, cleaved-caspase-3, PARP, cleaved-PARP, p-mTOR, and mTOR in PC12 cells in each group. Results. H2O2 treatment could significantly reduce PC12 cell viability and promote cell apoptosis and oxidative stress. PKN2 overexpression inhibited H2O2-induced apoptosis and oxidation damage by increasing PC12 cell viability, SOD activity, and p-mTOR protein expression, reducing intracellular ROS and MDA levels, and cleaved-caspase-3 and cleaved-PARP protein expression. Conclusion. PKN2 overexpression can alleviate H2O2-induced oxidative stress injury and apoptosis in PC12 cells by activating the mTOR pathway.

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Section: Resultsmentioning

confidence: 99%

Protein Kinase N2 Reduces Hydrogen Peroxide-inducedDamage and Apoptosis in PC12 Cells by AntiOxidative Stress and Activation of the mTOR Pathway

Wang

Zhang

2022

Evidence-Based Complementary and Alternative Medicine

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“…However, recent findings show that a significant pool of CyPA is an intra-mitochondrial factor, enhancing antiapoptotic signals, and hence suggesting a role in cell survival [20]. Indeed, CyPA was found to inhibit oxidative stress and apoptosis by modulating the PI3K/Akt/mTOR signaling pathway [21] in cancer cells. Here, we found that in response to Ivabradine, CyPA was accumulated in the necrotic area of pigs subjected to IR when compared to the placebo group.…”

Section: Discussionmentioning

confidence: 99%

Ivabradine Induces Cardiac Protection against Myocardial Infarction by Preventing Cyclophilin-A Secretion in Pigs under Coronary Ischemia/Reperfusion

Hernández

Tesoro

Ramírez-Carracedo

et al. 2021

IJMS

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In response to cardiac ischemia/reperfusion, proteolysis mediated by extracellular matrix metalloproteinase inducer (EMMPRIN) and its secreted ligand cyclophilin-A (CyPA) significantly contributes to cardiac injury and necrosis. Here, we aimed to investigate if, in addition to the effect on the funny current (I(f)), Ivabradine may also play a role against cardiac necrosis by reducing EMMPRIN/CyPA-mediated cardiac inflammation. In a porcine model of cardiac ischemia/reperfusion (IR), we found that administration of 0.3 mg/kg Ivabradine significantly improved cardiac function and reduced cardiac necrosis by day 7 after IR, detecting a significant increase in cardiac CyPA in the necrotic compared to the risk areas, which was inversely correlated with the levels of circulating CyPA detected in plasma samples from the same subjects. In testing whether Ivabradine may regulate the levels of CyPA, no changes in tissue CyPA were found in healthy pigs treated with 0.3 mg/kg Ivabradine, but interestingly, when analyzing the complex EMMPRIN/CyPA, rather high glycosylated EMMPRIN, which is required for EMMPRIN-mediated matrix metalloproteinase (MMP) activation and increased CyPA bonding to low-glycosylated forms of EMMPRIN were detected by day 7 after IR in pigs treated with Ivabradine. To study the mechanism by which Ivabradine may prevent secretion of CyPA, we first found that Ivabradine was time-dependent in inhibiting co-localization of CyPA with the granule exocytosis marker vesicle-associated membrane protein 1 (VAMP1). However, Ivabradine had no effect on mRNA expression nor in the proteasome and lysosome degradation of CyPA. In conclusion, our results point toward CyPA, its ligand EMMPRIN, and the complex CyPA/EMMPRIN as important targets of Ivabradine in cardiac protection against IR.

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“…Activation of the CypA/CD147 interaction inhibits the apoptosis of cancer cells [ 13 , 54 , 75 , 76 , 77 , 78 , 79 , 80 , 81 ]. The antiapoptotic effects are associated with the upregulation of the PI3K/AKT/mTOR signaling pathway, modulation of the Bcl-2 family, and inhibition of caspase cascades [ 13 , 54 , 78 , 79 ]. Overexpression of CypA prevents hypoxia- and cisplatin-induced apoptosis in several cancer cell lines, including prostate cancer cells [ 56 ].…”

Section: Roles Of Cypa/cd147 Interaction In Cancermentioning

confidence: 99%

Cyclophilin A/CD147 Interaction: A Promising Target for Anticancer Therapy

Han

Jung

2022

IJMS

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Cyclophilin A (CypA), which has peptidyl–prolyl cis-trans isomerase (PPIase) activity, regulates multiple functions of cells by binding to its extracellular receptor CD147. The CypA/CD147 interaction plays a crucial role in the progression of several diseases, including inflammatory diseases, coronavirus infection, and cancer, by activating CD147-mediated intracellular downstream signaling pathways. Many studies have identified CypA and CD147 as potential therapeutic targets for cancer. Their overexpression promotes growth, metastasis, therapeutic resistance, and the stem-like properties of cancer cells and is related to the poor prognosis of patients with cancer. This review aims to understand the biology and interaction of CypA and CD147 and to review the roles of the CypA/CD147 interaction in cancer pathology and the therapeutic potential of targeting the CypA/CD147 axis. To validate the clinical significance of the CypA/CD147 interaction, we analyzed the expression levels of PPIA and BSG genes encoding CypA and CD147, respectively, in a wide range of tumor types using The Cancer Genome Atlas (TCGA) database. We observed a significant association between PPIA/BSG overexpression and poor prognosis, such as a low survival rate and high cancer stage, in several tumor types. Furthermore, the expression of PPIA and BSG was positively correlated in many cancers. Therefore, this review supports the hypothesis that targeting the CypA/CD147 interaction may improve treatment outcomes for patients with cancer.

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Cyclophilin A inhibits A549 cell oxidative stress and apoptosis by modulating the PI3K/Akt/mTOR signaling pathway

Cited by 29 publications

References 57 publications

Protein Kinase N2 Reduces Hydrogen Peroxide-inducedDamage and Apoptosis in PC12 Cells by AntiOxidative Stress and Activation of the mTOR Pathway

Protein Kinase N2 Reduces Hydrogen Peroxide-inducedDamage and Apoptosis in PC12 Cells by AntiOxidative Stress and Activation of the mTOR Pathway

Ivabradine Induces Cardiac Protection against Myocardial Infarction by Preventing Cyclophilin-A Secretion in Pigs under Coronary Ischemia/Reperfusion

Cyclophilin A/CD147 Interaction: A Promising Target for Anticancer Therapy

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