JNK1 Deficient Insulin-Producing Cells Are Protected against Interleukin-1<i>β</i>-Induced Apoptosis Associated with Abrogated Myc Expression

Prause, Michala; Mayer, Christopher; Brorsson, Caroline; Frederiksen, Klaus Stensgaard; Billestrup, Nils; Størling, Joachim; Mandrup-Poulsen, Thomas

doi:10.1155/2016/1312705

Cited by 9 publications

(4 citation statements)

References 54 publications

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“…Rehab observed that the STZ-induced diabetes significantly increased the expression of the apoptosis biomarker C-fos gene [ 27 ]. Experimental studies have also confirmed that MYC, CASP3, JUN, and EGFR are related to islet β -cell apoptosis [ 28 ], while AKT1 acts as an antiapoptotic signaling kinase in a variety of cells. Zhang Rui found that increasing the expression of Akt in islet cells can reduce islet cell apoptosis and increase secretory function [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanism of the Effect of Huanglian Jiedu Decoction on Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking

Yin

Fan

et al. 2020

Journal of Diabetes Research

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Background. Huanglian Jiedu Decoction (HLJDD) is a Traditional Chinese Medicine (TCM) formula comprising four herbal medicines. This decoction has long been used in China for clinically treating T2DM. However, the molecular mechanism of HLJDD treat for T2DM is still not fully known. Hence, this study was designed to reveal the synergistic mechanism of HLJDD formula in the treatment of T2DM by using network pharmacology method and molecular docking. Methods. Retrieving and screening of active components of different herbs in HLJDD and corresponding T2DM-related target genes across multiple databases. Subsequently, STRING and Cytoscape were applied to analysis and construct PPI network. In addition, cluster and topological analysis were employed for the analysis of PPI networks. Then, the GO and KEGG enrichment analysis were performed by using ClueGO tool. Finally, the differentially expressed analysis was used to verify whether the expression of key target genes in T2DM and non-T2DM samples was statistically significant, and the binding capacity between active components and key targets was validated by molecular docking using AutoDock. Results. There are 65 active components involved in 197 T2DM-related targets that are identified in HLJDD formula. What is more, 39 key targets (AKT1, IL-6, FOS, VEGFA, CASP3, etc.) and 3 clusters were obtained after topological and cluster analysis. Further, GO and KEGG analysis showed that HLJDD may play an important role in treating T2DM and its complications by synergistically regulating many biological processes and pathways which participated in signaling transduction, inflammatory response, apoptotic process, and vascular processes. Differentially expressed analysis showed that AKT1, IL-6, and FOS were upregulated in T2DM samples and a significant between sample differential expression. These results were validated by molecular docking, which identified 5 high-affinity active components in HLJDD, including quercetin, wogonin, baicalein, kaempferol, and oroxylin A. Conclusion. Our research firstly revealed the basic pharmacological effects and relevant mechanisms of the HLJDD in the treatment of T2DM and its complications. The prediction results might facilitate the development of HLJDD or its active compounds as alternative therapy for T2DM. However, more pharmacological experiments should be performed for verification.

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Section: Discussionmentioning

confidence: 99%

Molecular Mechanism of the Effect of Huanglian Jiedu Decoction on Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking

Yin

Fan

et al. 2020

Journal of Diabetes Research

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“…Furthermore, Tau has better inhibitory effect toward the proliferation of P53−/− tumor cells than toward P53+/+ tumor cells [10], indicating that the Tau-induced apoptosis of cancer cells is not only related to the mitochondrial apoptotic pathway but also involves other apoptotic signaling pathways. Recent studies have found that MST1 [16] and JNK [17] play important roles in the occurrence and development of colon cancer; however, whether the MST1-JNK signaling pathway is involved in the Tau-induced apoptosis of CRC cells has not been reported till date. In the present study, the CRC cell lines, SW620 and Caco-2, were used as the study subjects, in which the expression of the MST1 gene was regulated and the JNK pathway was inhibited to investigate the effect of the MST1-JNK signaling pathway in Tau-induced apoptosis of CRC cells.…”

Section: Introductionmentioning

confidence: 99%

Roles of the MST1-JNK signaling pathway in apoptosis of colorectal cancer cells induced by Taurine

Liu

Xia

Zhang

et al. 2018

Libyan Journal of Medicine

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The aim of this study was to observe the impact of the mammalian sterile 20-like kinase 1-c-Jun N-terminal kinase (MST1-JNK) signaling pathway on apoptosis in colorectal cancer (CRC) cells induced by Taurine (Tau). Caco-2 and SW620 cells transfected with p-enhanced green fluorescent protein (EGFP)-MST1 or short interfering RNA (siRNA)-MST1 were treated with Tau for 48 h. Apoptosis was detected by flow cytometry, and the levels of MST1 and JNK were detected by western blotting. Compared with the control group, 80 mM Tau could significantly induce apoptosis of CRC cells, and the apoptotic rate increased with increasing Tau concentration (P < 0.01). Meanwhile, the protein levels of MST1 and phosphorylated (p)-JNK in Caco-2 cells increased significantly (P < 0.01). The apoptotic rate of the p-EGFP-MST1 plasmid-transfected cancer cells was significantly higher than that of the control group (P < 0.05); however, the apoptotic rate of the p-EGFP-MST1+Tau group was increased further (P < 0.01). Silencing the MST1 gene could decrease the apoptotic rate of cancer cells, and Tau treatment could reverse this decrease. Blocking the JNK signaling pathway significantly reduced the Tau-induced apoptotic rate of CRC cells. Thus, the MST1-JNK pathway plays an important role in Tau-induced apoptosis of CRC cells.

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“…C-MYC is a potential downstream molecule of JNK1-mediated apoptosis [ 17 ], and the apoptotic role of C-MYC depends on C-MYC overexpression and apoptotic pathway activation [ 18 ]. Our results revealed that ARF and P53 expression was upregulated following the upregulation of C-MYC.…”

Section: Resultsmentioning

confidence: 99%

BAX as the mediator of C-MYC sensitizes acute lymphoblastic leukemia to TLR9 agonists

Bai

Han²,

Chen³

et al. 2023

J Transl Med

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Background The prognosis of B-cell acute lymphoblastic leukemia (B-ALL) has improved significantly with current first-line therapy, although the recurrence of B-ALL is still a problem. Toll-like receptor 9 (TLR9) agonists have shown good safety and efficiency as immune adjuvants. Apart from their immune regulatory effect, the direct effect of TLR9 agonists on cancer cells with TLR9 expression cannot be ignored. However, the direct effect of TLR9 agonists on B-ALL remains unknown. Methods We discussed the relationship between TLR9 expression and the clinical characteristics of B-ALL and explored whether CpG 685 exerts direct apoptotic effect on B-ALL without inhibiting normal B-cell function. By using western blot, co-immunoprecipitation, immunofluorescence co-localization, and chromatin immunoprecipitation, we explored the mechanism of the apoptosis-inducing effect of CpG 685 in treating B-ALL cells. By exploring the mechanism of CpG 685 on B-ALL, the predictive biomarkers of the efficacy of CpG 685 in treating B-ALL were explored. These efficiencies were also confirmed in mouse model as well as clinical samples. Results High expression of TLR9 in B-ALL patients showed good prognosis. C-MYC-induced BAX activation was the key to the effect of CpG oligodeoxynucleotides against B-ALL. C-MYC overexpression promoted P53 stabilization, enhanced Bcl-2 associated X-protein (BAX) activation, and mediated transcription of the BAX gene. Moreover, combination therapy using CpG 685 and imatinib, a BCR-ABL kinase inhibitor, could reverse resistance to CpG 685 or imatinib alone by promoting BAX activation and overcoming BCR-ABL1-independent PI3K/AKT activation. Conclusion TLR9 is not only a prognostic biomarker but also a potential target for B-ALL therapy. CpG 685 monotherapy might be applicable to Ph− B-ALL patients with C-MYC overexpression and without BAX deletion. CpG 685 may also serve as an effective combinational therapy against Ph+ B-ALL.

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JNK1 Deficient Insulin-Producing Cells Are Protected against Interleukin-1β-Induced Apoptosis Associated with Abrogated Myc Expression

Cited by 9 publications

References 54 publications

Molecular Mechanism of the Effect of Huanglian Jiedu Decoction on Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking

Molecular Mechanism of the Effect of Huanglian Jiedu Decoction on Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking

Roles of the MST1-JNK signaling pathway in apoptosis of colorectal cancer cells induced by Taurine

BAX as the mediator of C-MYC sensitizes acute lymphoblastic leukemia to TLR9 agonists

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