Novel potential of tunicamycin as an activator of the aryl hydrocarbon receptor – dioxin responsive element signaling pathway

Horikawa, Kyohei; Oishi, Naoki; Nakagawa, Jin; Kasai, Ayumi; Hayakawa, Kunihiro; Hiramatsu, Naoki; Takano, Yosuke; Yokouchi, Makiko; Yao, Jian; Kitamura, Masanori

doi:10.1016/j.febslet.2006.05.061

Cited by 4 publications

(3 citation statements)

References 15 publications

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“…(56) It is also possible that the ER stress response during colitis facilitates AhR signaling and their reciprocal induction leads to the inflammatory response associated with DSS induced colitis. (57)…”

Section: Discussionmentioning

confidence: 99%

Role of the xenobiotic receptor in inflammatory bowel disease

Arsenescu

Zhong

et al. 2011

Inflammatory Bowel Diseases

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Background Gene-environment interplay modulates Inflammatory Bowel Diseases [IBD]. Dioxin-like compounds can activate the Aryl Hydrocarbon Receptor [AhR] and alter macrophage function as well as T cell polarization. We hypothesized that attenuation of the AhR signaling pathway will ameliorate colitis in a murine model of IBD. Design DSS colitis was induced in C57BL/6 AhR null mice [AhR −/−], heterozygous mice [AhR−/+], and their wild type [WT] littermates. Clinical and morphopathological parameters were used to compare the groups. Patients: AhR pathway activation was analyzed in biopsy specimens from 25 IBD patients and 15 healthy controls. Results AhR −/− mice died before the end of the treatment. However, AhR −/+ mice exhibited decreased disease activity compared to WT mice. The AhR −/+ mice expressed less proinflammatory cytokines such as TNFα (6.1 versus 15.7 fold increase) and IL17 (23.7 versus 67.9 fold increase) and increased antiinflammatory IL-10 (2.3 fold increase) compared with the AhR+/+ mice in the colon. Colonic macrophage infiltration was attenuated in the AhR −/+ group. AhR and its downstream targets were significantly upregulated in IBD patients versus control (CYP1A1 – 19.9, and IL8-10 fold increase). Conclusion Attenuation of the AhR receptor expression resulted in a protective effect during DSS-induced colitis, while the absence of AhR exacerbated the disease. Abnormal AhR pathway activation in the intestinal mucosa of IBD patients may promote chronic inflammation. Modulation of AhR signaling pathway via the diet, cessation of smoking or administration of AhR antagonists could be viable strategies for the treatment of IBD.

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Section: Discussionmentioning

confidence: 99%

Role of the xenobiotic receptor in inflammatory bowel disease

Arsenescu

Zhong

et al. 2011

Inflammatory Bowel Diseases

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“…Exposure groups were prepared in HBSS buffer (LuBioScience, Lucerne, Switzerland), and a solvent concentration of 0.5% DMSO (Sigma Aldrich, Buchs, Switzerland). Tunicyamycin (Enzo Lifescience, Lausen, Switzerland) is a known ER stress inducer and was furthermore found to induce CYP1A [ 27 ]. Afterwards, the liver was fixed in RNA Later (Qiagen, Basel, Switzerland), RNA was extracted, cDNA synthesized, and qRT-PCR performed (see Section 5.9).…”

Section: Methodsmentioning

confidence: 99%

Anti-Inflammatory Activity of Cyanobacterial Serine Protease Inhibitors Aeruginosin 828A and Cyanopeptolin 1020 in Human Hepatoma Cell Line Huh7 and Effects in Zebrafish (Danio rerio)

Faltermann

Hutter

Christen

et al. 2016

Toxins

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Intensive growth of cyanobacteria in freshwater promoted by eutrophication can lead to release of toxic secondary metabolites that may harm aquatic organisms and humans. The serine protease inhibitor aeruginosin 828A was isolated from a microcystin-deficient Planktothrix strain. We assessed potential molecular effects of aeruginosin 828A in comparison to another cyanobacterial serine protease inhibitor, cyanopeptolin 1020, in human hepatoma cell line Huh7, in zebrafish embryos and liver organ cultures. Aeruginosin 828A and cyanopeptolin 1020 promoted anti-inflammatory activity, as indicated by transcriptional down-regulation of interleukin 8 and tumor necrosis factor α in stimulated cells at concentrations of 50 and 100 µmol·L−1 aeruginosin 828A, and 100 µmol·L−1 cyanopeptolin 1020. Aeruginosin 828A induced the expression of CYP1A in Huh7 cells but did not affect enzyme activity. Furthermore, hatched zebrafish embryos and zebrafish liver organ cultures were exposed to aeruginosin 828A. The transcriptional responses were compared to those of cyanopeptolin 1020 and microcystin-LR. Aeruginosin 828A had only minimal effects on endoplasmic reticulum stress. In comparison to cyanopeptolin 1020 our data indicate that transcriptional effects of aeruginosin 828A in zebrafish are very minor. The data further demonstrate that pathways that are influenced by microcystin-LR are not affected by aeruginosin 828A.

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“…Our results may indicate that the observed effect of inhibition of CSFV propagation by low doses of tunicamycin may be caused by some other mechanisms than N-glycosylation inhibition. It has been reported that low doses of tunicamycin affect cellular receptors and signal transduction (Mauro et al, 2003;Horikawa et al, 2006) and these effects may inhibit proper transport of viral components and virus maturation.…”

Section: In Situ Analysis Of Localization Of Csfv Glycoproteins In Skmentioning

confidence: 99%

Effect of N-glycosylation inhibition on the synthesis and processing of classical swine fever virus glycoproteins.

2007

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Classical swine fever virus (CSFV) is often used as a surrogate model in molecular studies of the closely related hepatitis C virus. In this report we have examined the effect of the inhibition of glycosylation on the survival and maturation of CSFV. Viral glycoproteins (E(rns), E1, E2) form biologically active complexes - homo- and heterodimers, which are indispensable for viral life cycle. Those complexes are highly N-glycosylated. We studied the influence of N-glycosylation on dimer formation using E(rns) and E2 glycoproteins produced in insect cells after infection with recombinant baculoviruses. The glycoproteins were efficiently synthesized in insect cells, had similar molecular masses and formed dimers like their natural counterparts. Surprisingly, the addition of tunicamycin (an antibiotic which blocks early steps of glycosylation) to insect cell culture blocked not only dimer formation but it also led to an almost complete disappearance of E2 even in monomeric form. Tunicamycin did not exert a similar effect on the synthesis and formation of E(rns) dimers; the dimers were still formed, which suggests that E(rns) glycan chains are not necessary for dimer formation. We have also found that very low doses of tunicamycin (much lower than those used for blocking N-glycosylation) drastically reduced CSFV spread in SK6 (swine kidney) cell culture and the virus yield. These facts indicate that N-glycosylation inhibitors structurally similar to tunicamycin may be potential therapeutics for the inhibition of the spread of CSFV and related viruses.

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Novel potential of tunicamycin as an activator of the aryl hydrocarbon receptor – dioxin responsive element signaling pathway

Cited by 4 publications

References 15 publications

Role of the xenobiotic receptor in inflammatory bowel disease

Role of the xenobiotic receptor in inflammatory bowel disease

Anti-Inflammatory Activity of Cyanobacterial Serine Protease Inhibitors Aeruginosin 828A and Cyanopeptolin 1020 in Human Hepatoma Cell Line Huh7 and Effects in Zebrafish (Danio rerio)

Effect of N-glycosylation inhibition on the synthesis and processing of classical swine fever virus glycoproteins.

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