NF-κB/mTOR-mediated autophagy can regulate diquat-induced apoptosis

Park, Aeri; Koh, Hyun Chul

doi:10.1007/s00204-019-02424-7

Cited by 49 publications

(28 citation statements)

References 49 publications

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“…mTOR regulates the transport of amino acid transporters in human trophoblasts by mediating Rac1 and Cdc42 (46). mTOR-mediated autophagy regulates the apoptosis induced by diquat (47). Our experimental results demonstrated that p-mTOR was highly expressed in RMS and that the inhibition of mTOR in RMS cell lines promoted apoptosis and autophagy, and this finding was consistent with the idea that mTOR inhibited apoptosis and autophagy in renal carcinoma (48).…”

Section: Discussionsupporting

confidence: 87%

GEFT Inhibits Autophagy and Apoptosis in Rhabdomyosarcoma via Activation of the Rac1/Cdc42-mTOR Signaling Pathway

Song

et al. 2021

Front. Oncol.

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Autophagy and apoptosis are dynamic processes that determine the fate of cells, and regulating these processes can treat cancer. GEFT is highly expressed in rhabdomyosarcoma (RMS), which accelerates the tumorigenicity and metastasis of RMS by activating Rac1/Cdc42 signaling, but the regulatory mechanisms of autophagy and apoptosis are unclear. In our study, we found that the RMS tissues had high Rac1, Cdc42, mTOR, and Bcl-2 expression levels and low Beclin1, LC3, and Bax expression levels compared with the normal striated muscle tissues (P < 0.05). In addition, multivariate analysis has proven that Rac1 is an independent prognostic factor (P < 0.05), and the high expression level of the Beclin1 protein was closely associated with the tumor diameter of the RMS patients (P = 0.044), whereas the high expression level of the LC3 protein was associated with the clinical stage of the RMS patients (P = 0.027). Furthermore, GEFT overexpression could inhibit autophagy and apoptosis in RMS. A Rac1/Cdc42 inhibitor was added, and the inhibition of autophagy and apoptosis decreased. Rac1 and Cdc42 could regulate mTOR to inhibit autophagy and apoptosis in RMS. Overall, these studies demonstrated that the GEFT–Rac1/Cdc42–mTOR pathway can inhibit autophagy and apoptosis in RMS and provide evidence for innovative treatments.

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Section: Discussionsupporting

confidence: 87%

GEFT Inhibits Autophagy and Apoptosis in Rhabdomyosarcoma via Activation of the Rac1/Cdc42-mTOR Signaling Pathway

Song

et al. 2021

Front. Oncol.

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“…Indeed, the relationship between the autophagy and NF‐κB pathway has caught the attention of many researchers. It has been demonstrated that suppression of NF‐κB could induce autophagy (Zhu et al, 2019), while it also has been shown that inhibition of NF‐κB resulted in diminishing LC3‐II and suppression of autophagy (Park & Koh, 2019). Recent studies have further explained the molecular mechanisms of autophagy inhibiting IL‐1β‐induced apoptosis (J. Zhang et al, 2020; Zou et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Curcumin ameliorates IL‐1β‐induced apoptosis by activating autophagy and inhibiting the NF‐κB signaling pathway in rat primary articular chondrocytes

Chen

Zhou

Chen

et al. 2021

Cell Biology International

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Articular cartilage damage and chondrocyte apoptosis are common features of rheumatoid arthritis and osteoarthritis. Recently, curcumin has been reported to exhibit protective effects on degeneration in articular cartilage diseases. However, the effects and mechanisms of curcumin on articular chondrocyte injury remain to be elucidated. The aim of the present study is to investigate the chondroprotective mechanisms of curcumin on interleukin‐1β (IL‐1β)‐induced chondrocyte apoptosis in vitro. The results revealed that IL‐1β decreased cell viability and induced apoptosis in primary articular chondrocytes. Curcumin pretreatment reduced IL‐1β‐induced articular chondrocyte apoptosis. In addition, treatment with curcumin increased autophagy in articular chondrocytes and protected against IL‐1β‐induced apoptosis. The curcumin‐mediated protection against IL‐1β induced apoptosis was abolished when cells were treated with the autophagy inhibitor 3‐methyladenine or transfected with Beclin‐1 small interfering RNA. Furthermore, IL‐1β stimulation significantly increased the phosphorylation levels of nuclear factor (NF)‐κB p65 and glycogen synthase kinase‐3β, and decreased the phosphorylation levels of β‐catenin in articular chondrocytes, and these alterations to the phosphorylation levels were partly reversed by treatment with curcumin. Dual‐luciferase and electrophoretic mobility shift assays demonstrated that IL‐1β increased NF‐κB p65 promoter activity in chondrocytes, and this was also reversed by curcumin. Pretreatment with the NF‐κB inhibitor pyrrolidine dithiocarbamate enhanced the protective effects of curcumin on chondrocyte apoptosis, but Wnt/β‐catenin inhibitor, XAV‐939, did not exhibit this effect. Molecular docking and dynamic simulation studies results showed that curcumin could bound to RelA (p65) protein. These results indicate that curcumin may suppress IL‐1β‐induced chondrocyte apoptosis through activating autophagy and restraining NF‐κB signaling pathway.

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“…57 NAC reduces the expression of cleaved-caspase-3 and cleaved-caspase-9 caused by diquat toxicity in rat pheochromocytoma PC12 cells. 58 NAC also reverses sanguinarine-induced apoptosis by promoting Bcl2 expression in HSC-T6 rat hepatic stellate cells. 59 Consistent with the above studies, NAC reduced the expression of cleaved-caspase-3, promoted Bcl2 expression, and reduced DA death in MPP+-treated MN9D cells.…”

Section: Discussionmentioning

confidence: 93%

“…In SH‐SY5Y cells, the thiol antioxidant NAC, a proverbial oxidation inhibitor, reduces MPP + ‐induced mitochondrial fragmentation and ROS production 57 . NAC reduces the expression of cleaved‐caspase‐3 and cleaved‐caspase‐9 caused by diquat toxicity in rat pheochromocytoma PC12 cells 58 . NAC also reverses sanguinarine‐induced apoptosis by promoting Bcl2 expression in HSC‐T6 rat hepatic stellate cells 59 .…”

Section: Discussionmentioning

confidence: 99%

Tristetraprolin destabilizes NOX2 mRNA and protects dopaminergic neurons from oxidative damage in Parkinson's disease

et al. 2020

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Tristetraprolin (TTP), an RNA-binding protein encoded by the ZFP36 gene, is vital for neural differentiation; however, its involvement in neurodegenerative diseases such as Parkinson's disease (PD) remains unclear. To explore the role of TTP in PD, an in vitro 1-methyl-4-phenylpyridinium (MPP +) cell model and an in vivo 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) of PD were used. Transfection of small interfering (si)-TTP RNA upregulated pro-oxidative NOX2 expression and ROS formation, downregulated anti-oxidative GSH and SOD activity；si-TTP upregulated pro-apoptotic cleaved-caspase-3 expression, and downregulated antiapoptotic Bcl-2 expression; while overexpression (OE)-TTP lentivirus caused opposite effects. Through database prediction, luciferase experiment, RNA immunoprecipitation (RIP), and mRNA stability analysis, we evaluated the potential binding sites of TTP to 3′-untranslated regions (3′-UTR) of NOX2 mRNA. TTP affected the NOX2 luciferase activity by binding to two sites in the NOX2 3′-UTR. RIP-qPCR confirmed TTP binding to both sites, with a higher affinity for site-2. In addition, TTP reduced the NOX2 mRNA stability. si-NOX2 and antioxidant N-acetyl cysteine (NAC) reversed si-TTP-induced cell apoptosis. In MPTP-treated mice, TTP expression increased and was co-located with dopaminergic neurons. TTP also inhibited NOX2 and decreased the oxidative stress in vivo. In conclusion, TTP protects against dopaminergic oxidative injury by promoting NOX2 mRNA 15048 | SUN et al.

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NF-κB/mTOR-mediated autophagy can regulate diquat-induced apoptosis

Cited by 49 publications

References 49 publications

GEFT Inhibits Autophagy and Apoptosis in Rhabdomyosarcoma via Activation of the Rac1/Cdc42-mTOR Signaling Pathway

GEFT Inhibits Autophagy and Apoptosis in Rhabdomyosarcoma via Activation of the Rac1/Cdc42-mTOR Signaling Pathway

Curcumin ameliorates IL‐1β‐induced apoptosis by activating autophagy and inhibiting the NF‐κB signaling pathway in rat primary articular chondrocytes

Tristetraprolin destabilizes NOX2 mRNA and protects dopaminergic neurons from oxidative damage in Parkinson's disease

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