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所属 |
農学部 海洋生物環境学科 |
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職名 |
准教授 |
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Reactive oxygen species are associated with the inhibitory effect of N-(4-hydroxyphenyl)-retinamide on the entry of the severe acute respiratory syndrome-coronavirus 2. 査読あり
Hayashi Y, Huang X, Tanikawa T, Tanigawa K, Yamamoto M, Gohda J, Inoue JI, Fukase K, Kabayama K.
The Journal of Biochemistry 2023年3月
担当区分：筆頭著者, 責任著者 記述言語：英語 掲載種別：研究論文（学術雑誌）
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Tanikawa T., Kitamura M., Hayashi Y., Tomida N., Uwaya A., Isami F., Yokogawa T., Inoue Y.
In vivo (Athens, Greece) 37 ( 2 ) 591 - 595 2023年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：In vivo (Athens, Greece)
BACKGROUND/AIM: The inflammatory response plays an important role in the activation and progression of many inflammation-related diseases. Cannabis sativa and Morinda citrifolia have long been used in folk medicine to treat inflammation. Cannabidiol is the most abundant non-psychoactive phytocannabinoid in C. sativa and exhibits anti-inflammatory activity. The objective of this study was to examine the anti-inflammatory effect of cannabidiol in combination with M. citrifolia and compare its effects with those of cannabidiol alone. MATERIALS AND METHODS: RAW264 cells stimulated with lipopolysaccharide (200 ng/ml) were treated with cannabidiol (0-10 μM), M. citrifolia seed extract (0-100 μg/ml), or a combination of both for 8 or 24 h. Following the treatments, nitric oxide production in the activated RAW264 cells and the expression of inducible nitric oxide synthase were assessed. RESULTS: Our results showed that combination of cannabidiol (2.5 μM) and M. citrifolia seed extract (100 μg/ml) exhibited more efficient inhibition of nitric oxide production than cannabidiol treatment alone in lipopolysaccharide-stimulated RAW264 cells. The combination treatment also reduced the expression of inducible nitric oxide synthase. CONCLUSION: These results suggest that the anti-inflammatory effect of combined treatment with cannabidiol and M. citrifolia seed extract causes a reduction in the expression of inflammatory mediators.
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Dihydroceramide Δ4-Desaturase 1 Is Not Involved in SARS-CoV-2 Infection 査読あり
Hayashi Y., Matsuda K., Tanigawa K., Tanikawa T., Maeda K., Tsuchiya K.
Biological and Pharmaceutical Bulletin 45 ( 10 ) 1559 - 1563 2022年10月
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Biological and Pharmaceutical Bulletin
Dihydroceramide Δ4-desaturase 1 (DEGS1) enzymatic activity is inhibited with N-(4-hydroxyphenyl)retinamide (4-HPR). We reported previously that 4-HPR suppresses severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry through a DEGS1-independent mechanism. However, it remains unclear whether DEGS1 is involved in other SARS-CoV-2 infection processes, such as virus replication and release. Here we established DEGS1 knockout (KO) in VeroE6TMPRSS2 cells. No significant difference was observed in virus production in the culture supernatant between wild-type (WT) cells and DEGS1-KO cells, although the levels of dihydroceramide (DHCer), a DEGS1 substrate, were significantly higher in DEGS1-KO cells than WT cells. Furthermore, the virus-induced cytopathic effect was also observed in DEGS1-KO cells. Importantly, the EC50 value of 4-HPR in DEGS1-KO cells was almost identical to the value reported previously in WT cells. Our results indicated the lack of involvement of DEGS1 in SARS-CoV-2 infection.
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Tanigawa K., Kiriya M., Hayashi Y., Shinden Y., Kijima Y., Natsugoe S., Sumimoto T., Morimoto-Kamata R., Yui S., Hama K., Yokoyama K., Nakamura Y., Suzuki K., Nojiri H., Inoue K., Karasawa K.
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids 1867 ( 8 ) 2022年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Breast cancer is primarily classified into ductal and lobular types, as well as into noninvasive and invasive cancer. Invasive cancer involves lymphatic and hematogenous metastasis. In breast cancer patients with distant metastases, a neutrophil-derived serine protease; cathepsin G (Cat G), is highly expressed in breast cancer cells. Cat G induces cell migration and multicellular aggregation of MCF-7 human breast cancer cells; however, the mechanism is not clear. Recently, platelet-activating factor (PAF)-acetylhydrolase (PAF-AH), the enzyme responsible for PAF degradation, was reported to be overexpressed in some tumor types, including pancreatic and breast cancers. In this study, we investigated whether PAF-AH is involved in Cat G-induced aggregation and migration of MCF-7 cells. We first showed that Cat G increased PAF-AH activity and elevated PAFAH1B2 expression in MCF-7 cells. The elevated expression of PAFAH1B2 was also observed in human breast cancer tissue specimens by immunohistochemical analysis. Furthermore, knockdown of PAFAH1B2 in MCF-7 cells suppressed the cell migration and aggregation induced by low concentrations, but not high concentrations, of Cat G. Carbamoyl PAF (cPAF), a nonhydrolyzable PAF analog, completely suppressed Cat G-induced migration of MCF-7 cells. In addition, PAF receptor (PAFR) inhibition induced cell migration of MCF-7 cells even in the absence of Cat G, suggesting that Cat G suppresses the activation of PAFR through enhanced PAF degradation due to elevated expression of PAFAH1B2 and thereby induces malignant phenotypes in MCF-7 cells. Our findings may lead to a novel therapeutic modality for treating breast cancer by modulating the activity of Cat G/PAF signaling.
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Tanikawa T., Kitamura M., Hayashi Y., Yokogawa T., Inoue Y.
In Vivo 36 ( 1 ) 227 - 232 2022年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：In Vivo
Background/Aim: The cannabinoid 2 (CB2) receptor is an important regulator of immunoinflammatory responses. Crude drugs commonly used in Japanese traditional Kampo medicine have displayed anti-inflammatory effects; however, few studies have reported that these effects are mediated via CB2 receptor signaling. Therefore, this study aimed to elucidate CB2 receptor-related anti-inflammatory regulation in crude drugs. Materials and Methods: The ethanol extracts of 34 crude drugs listed in the Japanese Pharmacopeia were tested, and the inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production were evaluated in murine macrophage RAW 264 cells. Results: The extracts of Curcumae Longae Rhizoma (dried rhizome of Curcuma longa) and Saussureae Radix (dried root of Saussurea lappa) significantly inhibited NO production and attenuated the LPS-induced decrease in CB2 receptor mRNA expression. Conclusion: Curcumae Longae Rhizoma and Saussureae Radix can modulate the CB2-receptor-related anti-inflammatory regulation in macrophages.