Suppression of µ1 subunit of the adaptor protein complex 2 reduces dengue virus release

Tongmuang, Nopprarat; Yasamut, Umpa; Noisakran, Sansanee; Sreekanth, Gopinathan Pillai; Yenchitsomanus, Pa‐thai; Limjindaporn, Thawornchai

doi:10.1007/s11262-019-01710-x

Cited by 7 publications

(6 citation statements)

References 45 publications

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“…In the current study, we applied pre-, co- and post-treatments together, only aiming to identify whether crocetin treatment has any effect on DENV replication or host response, or both. In DENV-infected Huh7 cells, the effects of pre-, co- and post-treatment of sunitinib were explained [ 41 ]. Our study in DENV-infected mice has this limitation, and more detailed studies are required to investigate the impact of crocetin treatment with pre-, co- or post-treatments, or their synergistic treatment options, and determine which treatment strategy works the best.…”

Section: Discussionmentioning

confidence: 99%

Crocetin Improves Dengue Virus-Induced Liver Injury

Sreekanth

Chuncharunee

Yenchitsomanus

et al. 2020

Viruses

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Dengue virus (DENV) infection is one of the most widespread mosquito-borne viral infections. Liver injury is commonly observed in severe DENV infection, and the present study aimed to examine the efficacy of crocetin treatment in an immunocompetent mouse model of DENV infection exhibiting liver injury. The efficacy of crocetin treatment in DENV-induced liver injury was assessed via both transaminase levels and histopathology analysis. A real-time polymerase chain reaction array was then used to describe the expression of 84 apoptosis-related genes. Using real-time RT-PCR and Western blot analysis, the gene expressions of host factors were investigated. Additionally, the effect of crocetin in NF-kB signaling during DENV infection was studied. We did not observe any significant reduction in virus production when DENV-infected mice were treated with crocetin. However, DENV-infected mice treated with crocetin showed reduced DENV-induced apoptosis. The real-time polymerase chain reaction array revealed pro-inflammatory cytokine expressions to be significantly reduced in the crocetin-treated DENV-infected mice. We also found that crocetin could effectively modulate antioxidant status in DENV-infected mice. Moreover, crocetin demonstrated the ability to reduce the nuclear translocation of NF-kB in DENV-infected mice. Our results suggest that crocetin treatment does not inhibit DENV replication in the liver of DENV-infected mice; however, we did find that crocetin improves host responses that reduce liver injury.

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Section: Discussionmentioning

confidence: 99%

Crocetin Improves Dengue Virus-Induced Liver Injury

Sreekanth

Chuncharunee

Yenchitsomanus

et al. 2020

Viruses

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“…Adaptor Related Protein Complex 2 Subunit Mu 1 (AP2M1) is a protein coding gene, encoding a subunit of the heterotetrameric coat assembly protein complex 2 (AP2), which is required for the activity of a vacuolar ATPase and may also play an important role in regulating the intracellular trafficking and function of CTLA‐4 protein 8 . AP2M1 has been demonstrated to play critical roles in lipoprotein metabolism 9 and various virus infections, including hepatitis C virus, 10 Epstein–Barr virus, and human immunodeficiency virus 11 . Previous studies have shown that AP2M1 was a strong prognostic biomarker for hepatocellular carcinoma 12 and high expression of AP2M1 leads to inferior overall survival by mediating chemoresistance in acute myeloid leukemia (AML) 13 .…”

Section: Introductionmentioning

confidence: 99%

“…8 AP2M1 has been demonstrated to play critical roles in lipoprotein metabolism 9 and various virus infections, including hepatitis C virus, 10 Epstein-Barr virus, and human immunodeficiency virus. 11 Previous studies have shown that AP2M1 was a strong prognostic biomarker for hepatocellular carcinoma 12 and high expression of AP2M1 leads to inferior overall survival by mediating chemoresistance in acute myeloid leukemia (AML). 13 To the best of our knowledge, there are no reports on the relationship between DLBCL and AP2M1.…”

Section: Introductionmentioning

confidence: 99%

High expression of AP2M1 correlates with worse prognosis by regulating immune microenvironment and drug resistance to R‐CHOP in diffuse large B cell lymphoma

Liu

Zhao

Yang

et al. 2022

European J of Haematology

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Background: First-line treatment with R-CHOP has cured 50%-60% patients of diffuse large B cell lymphoma (DLBCL), and more than one-third patients will eventually progressed to relapsed/refractory disease with dismal outcomes. Adaptor Related Protein Complex 2 Subunit Mu 1 (AP2M1) is required for the activity of a vacuolar ATPase and may also play an important role in regulating the intracellular trafficking and function of CTLA-4 protein. Herein, using both public databases and our own tumor samples, we aimed to demonstrate the prognostic role of AP2M1 and the potential tumor-promoting mechanisms in DLBCL.Method: Using public datasets of DLBCL from both GEO and TCGA databases, we analyzed the role of AP2M1 in mediating chemoresistance to R-CHOP and its correlation with various clinical parameters and prognosis. By using various R packages, we evaluated the role of AP2M1 on regulating tumor immune microenvironment.Moreover, tumor samples of DLBCL from Beijing TongRen Hospital were used to validate our findings by immunohistochemistry staining.Result: Expression of AP2M1 was significantly increased in DLBCL, which was correlated with poor prognosis and a variety of clinical indicators. On the basis of enrichment analysis, it was found that AP2M1 may be related to intracellular receptor signaling pathway. Through immune analysis and drug prediction, we found that the expression of AP2M1 affected the immune environment and drug response of DLBCL, which further revealed the important role of AP2M1 in DLBCL. By analyzing 61 patients treated uniformly with R-CHOP regimen in our center, we validated the above findings that high expression of AP2M1 correlated with inferior survival outcomes and affected sensitivity to R-CHOP treatment. Conclusion: Expression of AP2M1 may affect the prognosis of DLBCL patients prob-ably by affecting the immune environment and the responses to many drugs in treating DLBCL, indicating AP2M1 as a potential therapy target in DLBCL.

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“…AP2M1 is one of the most important cytoplasmic carrier domains in clathrin-mediated endocytosis and the phosphorylation of this subunit stimulates clathrin and supports the cell surface receptor incorporation. AP2M1 is required for hepatitia C virus, rabies virus and dengue virus infection, and AP2M1 knockdown reduces viral titer or infectivity [13][14][15]. Moreover, abnormal AP2M1 causes developmental and epileptic encephalopathy through impairing clathrinmediated endocytosis [16].…”

Section: Introductionmentioning

confidence: 99%

Alantolactone inhibits cell autophagy and promotes apoptosis through targeting AP2M1 in acute lymphotic leukemia

Shi¹,

Wang²,

Yang³

et al. 2020

Preprint

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Abstract Background: Acute lymphoblastic leukemia (ALL) is an aggressive hematopoietic malignancy that is most common in children. Alantolactone (ALT) has been reported to have antitumor activity in different types of cancers. This study aimed to investigate the antitumor activity and molecular mechanism of ALT in ALL. Methods: The ALL cell lines were treated with 1, 5 and 10μM of ALT, and then subjected to MTT assay and RNA sequencing. Flow cytometry, JC-1 staining and immunofluorescence staining assays were employed to measure cell apoptosis and autophagy. Meanwhile, Western blot analysis was used to detect apoptosis and autophagy related proteins. Finally, the effect of ALT on tumor growth was measured in BV173 xenograft nude mouse model. Results: In this study, we demonstrated that ALT inhibited the proliferation of ALL cells in does-dependent manner. A series of experiments demonstrated that ALT inhibited cell proliferation, colony formation, autophagy, induced apoptosis and restained tumor growth in vivo through upregulating adaptor related protein complex 2 subunit mu 1 (AP2M1). Moreover, autophagy activator rapamycin attenuated the pro-apoptotic effect of ALT on BV173 and NALM6 cell lines. Further, overexpressed AP2M1 decreased the expression of Beclin1, LC3-II/LC3-1 ratio and increased p62 expression. Fianally, knockdown of Beclin1 increased the levels of bax, cleaved caspase 3 and cytochrome C and decreased bcl-2 expression. Conclusions: This study demonstrated that ALT exerts antitumor activity through inducing apoptosis and inhibiting autophagy by upregulating AP2M1 in ALL, indicating a potential therapeutic strategy for ALL treatment.

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Suppression of µ1 subunit of the adaptor protein complex 2 reduces dengue virus release

Cited by 7 publications

References 45 publications

Crocetin Improves Dengue Virus-Induced Liver Injury

Crocetin Improves Dengue Virus-Induced Liver Injury

High expression of AP2M1 correlates with worse prognosis by regulating immune microenvironment and drug resistance to R‐CHOP in diffuse large B cell lymphoma

Alantolactone inhibits cell autophagy and promotes apoptosis through targeting AP2M1 in acute lymphotic leukemia

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