• 제목/요약/키워드: Tat pathway

검색결과 16건 처리시간 0.017초

Emodin Attenuates Inflammasome Activation Induced by Helicobacter pylori Infection through Inhibition of VacA Translocation

  • Thach Phan Van;Anh Duy Do
    • Microbiology and Biotechnology Letters
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    • 제51권4호
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    • pp.507-516
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    • 2023
  • Eradication of Helicobacter pylori infection is an essential strategy to decrease the risk of developing gastric cancer. However, the standard triple therapy has negative aspects associated with side effects and the emergence of antibiotic resistance. Therefore, alternative therapies are required to enhance the management of H. pylori infection effectively. In this study we examined the effect of emodin on the amelioration of inflammatory response due to H. pylori infection. Our results indicated that emodin treatment effectively decreased the expression of virulence genes, including sabA, vacA, cagL, cagA, sabA, and suppressed the adhesion ability of H. pylori to AGS cells. Emodin has been shown inhibitory effects on the inflammasome pathway through reductions in VacA translocation, lowering ROS stress, cleaved Caspase-1, NLRP3, and cleaved Gasdermin D levels, thereby lowered pyroptosis in infected cells. In summary, our study demonstrated that emodin has the ability to attenuate inflammation caused by H. pylori by modulating virulence gene expression and decreasing VacA translocation. Further study is required to evaluate the therapeutic efficacy of emodin in treating H. pylori infection and better understand the underlying mechanisms.

Effects of Rudbeckia laciniata Extract on Phagocytosis of Serum-Opsonized Zymosan Particles in Macrophages (대식세포의 혈청으로 식균된 자이모잔의 탐식능에 대한 삼잎국화 추출물의 효과)

  • Kim, Jun-Sub
    • The Korean Journal of Food And Nutrition
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    • 제29권3호
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    • pp.341-346
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    • 2016
  • Phagocytosis is a primary and an essential step of host defense, and is triggered by the interaction of particles with specific receptor of macrophages. In this study, we investigated the effect of extracts of Rudbeckia laciniata (RLE) on the phagocytic activity of macrophage, by monitoring the phagocytosis-associated signal transduction. RLE markedly increased phagocytosis of serum-opsonized zymosan particles (SOZ), while phagocytosis of IgG-opsonized zymosan particles (IOZ) or none-opsonized zymosan particles (NOZ) remained unaffected. However, RLE did not affect the binding of opsonized zymosan particles (OZ) with the cell surface of macrophage. This suggests that RLE may regulate SOZ-induced intracellular signaling during phagocytosis of macrophage. To confirm this hypothesis, we investigated whether RLE was involved in the RhoA-mediated signal transduction during phagocytosis of SOZ. Inhibitors of the RhoA-mediated signaling pathway, such as Y-27632 (for ROCK), ML-7 (for MLCK), and Tat-C3 (for RhoA), totally blocked phagocytosis of SOZ enhanced by RLE, as well as phagocytosis of SOZ. Additionally, RhoA activity was markedly increased when cells were treated with RLE, suggesting that RLE could increase the phagocytic activity of macrophage via RhoA-ROCK/MLCK signal pathway. Thus, RLE may be used to develop functional foods for immunity.

Lysophosphatidylcholine induces azurophil granule translocation via Rho/Rho kinase/F-actin polymerization in human neutrophils

  • Ham, Hwa-Yong;Kang, Shin-Hae;Song, Dong-Keun
    • The Korean Journal of Physiology and Pharmacology
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    • 제26권3호
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    • pp.175-182
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    • 2022
  • Translocation of azurophil granules is pivotal for bactericidal activity of neutrophils, the first-line defense cells against pathogens. Previously, we reported that lysophosphatidylcholine (LPC), an endogenous lipid, enhances bactericidal activity of human neutrophils via increasing translocation of azurophil granules. However, the precise mechanism of LPC-induced azurophil granule translocation was not fully understood. Treatment of neutrophil with LPC significantly increased CD63 (an azurophil granule marker) surface expression. Interestingly, cytochalasin B, an inhibitor of action polymerization, blocked LPC-induced CD63 surface expression. LPC increased F-actin polymerization. LPC-induced CD63 surface expression was inhibited by both a Rho specific inhibitor, Tat-C3 exoenzyme, and a Rho kinase (ROCK) inhibitor, Y27632 which also inhibited LPC-induced F-actin polymerization. LPC induced Rho-GTP activation. NSC23766, a Rac inhibitor, however, did not affect LPC-induced CD63 surface expression. Theses results suggest a novel regulatory mechanism for azurophil granule translocation where LPC induces translocation of azurophil granules via Rho/ROCK/F-actin polymerization pathway.

Gene Expression Profiling of Intrahepatic Cholangiocarcinoma

  • Subrungruang, Ittisak;Thawornkuno, Charin;Chawalitchewinkoon-Petmitr, Porntip;Pairojkul, Chawalit;Wongkham, Sopit;Petmitr, Songsak
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권1호
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    • pp.557-563
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    • 2013
  • Intrahepatic cholangiocarcinoma (ICC) is ranked as one of the top five causes of cancer-related deaths. ICC in Thai patients is associated with infection with the liver fluke, Opisthorchis viverrini, but the molecular basis for development remains unclear. The present study employed a microarray approach to compare gene expression profiles of ICCs and normal liver tissues from the same patients residing in Northeast Thailand, a region with a high prevalence of liver fluke infection. In ICC samples, 2,821 and 1,361 genes were found to be significantly up- and down-regulated respectively (unpaired t-test, p<0.05; fold-change ${\gep}2.0$). For validation of the microarray results, 7 up-regulated genes (FXYD3, GPRC5A, CEACAM5, MUC13, EPCAM, TMC5, and EHF) and 3 down-regulated genes (CPS1, TAT, and ITIH1) were selected for confirmation using quantitative RT-PCR, resulting in 100% agreement. The metallothionine heavy metal pathway contains the highest percentage of genes with statistically significant changes in expression. This study provides exon-level expression profiles in ICC that should be fruitful in identifying novel genetic markers for classifying and possibly early diagnosis of this highly fatal type of cholangiocarcinoma.

Extracellular Proteome Profiling of Bacillus pumilus SCU11 Producing Alkaline Protease for Dehairing

  • Wang, Chao;Yu, Shiqiang;Song, Ting;He, Tingting;Shao, Huanhuan;Wang, Haiyan
    • Journal of Microbiology and Biotechnology
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    • 제26권11호
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    • pp.1993-2005
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    • 2016
  • Bacillus pumilus is one of the most characterized microorganisms that are used for high-level production of select industrial enzymes. A novel B. pumilus SCU11 strain possessing high alkaline protease activity was obtained in our previous work. The culture supernatant of this strain showed efficient dehairing capability with minimal collagen damage, indicating promising potential applications in the leather industry. In this study, the strain's extracellular proteome was identified by LC-MS/MS-based shotgun proteomic analysis, and their related secretory pathways were characterized by BLAST searches. A total of 513 proteins, including 100 actual secreted and 413 intracellular proteins, were detected in the extracellular proteome. The functions of these secreted proteins were elucidated and four complete secretory systems (Sec, Tat, Com, and ABC transporter) were proposed for B. pumilus. These data provide B. pumilus a comprehensive extracellular proteome profile, which is a valuable theoretical and applicative basis for future genetic modifications and development of industrial enzymes.

Chelidonium majus Induces Apoptosis of Human Ovarian Cancer Cells via ATF3-Mediated Regulation of Foxo3a by Tip60

  • Shen, Lei;Lee, Soon;Joo, Jong Cheon;Hong, Eunmi;Cui, Zhen Yang;Jo, Eunbi;Park, Soo Jung;Jang, Hyun-Jin
    • Journal of Microbiology and Biotechnology
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    • 제32권4호
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    • pp.493-503
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    • 2022
  • Forkhead transcription factor 3a (Foxo3a) is believed to be a tumor suppressor as its inactivation leads to cell transformation and tumor development. However, further investigation is required regarding the involvement of the activating transcription factor 3 (ATF3)-mediated Tat-interactive protein 60 (Tip60)/Foxo3a pathway in cancer cell apoptosis. This study demonstrated that Chelidonium majus upregulated the expression of ATF3 and Tip60 and promoted Foxo3a nuclear translocation, ultimately increasing the level of Bcl-2-associated X protein (Bax) protein. ATF3 overexpression stimulated Tip60 expression, while ATF3 inhibition by siRNA repressed Tip60 expression. Furthermore, siRNA-mediated Tip60 inhibition significantly promoted Foxo3a phosphorylation, leading to blockade of Foxo3a translocation into the nucleus. Thus, we were able to deduce that ATF3 mediates the regulation of Foxo3a by Tip60. Moreover, siRNA-mediated Foxo3a inhibition suppressed the expression of Bax and subsequent apoptosis. Taken together, our data demonstrate that Chelidonium majus induces SKOV-3 cell death by increasing ATF3 levels and its downstream proteins Tip60 and Foxo3a. This suggests a potential therapeutic role of Chelidonium majus against ovarian cancer.