Researcher Database
Last Updated :2024/09/10
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Profile and Settings
Profile and Settings
Name (Japanese)
JOEName (Kana)
GA-HYUNName
201801011439894679
Achievement
Research Interests
Research Areas
Research Experience
- 2018/04 - Today Hokkaido University Faculty of Fisheries Sciences, Division of Marine Life Science
- 2017/10 - 2018/03 Hokkaido University Graduate School of Agriculture Research Faculty of Agriculture
- 2016/04 - 2017/09 日本学術振興会 特別研究員
Education
- 2014/10 - 2017/09 Hokkaido University Graduate School of Agriculture
- 2012/08 - 2014/09 Hokkaido University Graduate School of Agriculture
Awards
- 2021/11 8th International symposium East Asia Fisheries Technologists Association 2021 Best Oral Award
Enhanced anti-inflammatory activity of glycated salmon myofibrillar protein with reducing sugars containing carboxyl group,受賞者: Wenzhao Li*, Ga-Hyun Joe, Hiroki Saeki - 2021/11 8th International symposium East Asia Fisheries Technologists Association 2021 Best Oral Award
Development of bio-functionally enhanced collagen by alginate oligosaccharide glycation受賞者: Boxue Yang;Ga-Hyun Joe;Hiroki Saeki - 2020/12 2020年度日本農芸化学会北海道支部／第50回 日本栄養・食糧学 会北海道支部合同学術講演会 若手奨励賞
スケトウダラ筋肉水溶性タンパク質はマクロファージの受容体発現の変動を介してLPS誘導性炎症を抑制する受賞者: 大野 雅貴1,東(西澤) 瑞穂2,高橋 義宣2,小西 達也2,清水 裕1,趙 佳賢1,佐伯 宏樹1 (1北大院水,2マルハニチロ 中央研究所) - 2017/05 The International Conference of Korean Society of Food Science of Animal Resources and 49th Annual Meeting The Excellence Poster Presentation Award
- 2016/11 日本農芸化学会･北海道支部会 学生会員奨励賞受賞講演
Modulation of inflammatory responses by megalo-type isomaltoglucosaccharides受賞者: 趙 佳賢 - 2016/08 日本農芸化学会北海道支部平成28年度第1回講演会 優秀発表賞
受賞者: 趙 佳賢 - 2015/11 The 6th International Conference on Food Factors Poster Award受賞
受賞者: 趙 佳賢
Published Papers
- Wenzhao Li, Hiroki Saeki, Boxue Yang, Yutaka Shimizu, Ga-Hyun JoeFood Chemistry 141082 - 141082 0308-8146 2024/09 [Refereed]
- Wenzhao Li, Hiroki Saeki, Boxue Yang, Yutaka Shimizu, Ga‐Hyun JoeInternational Journal of Food Science and Technology 0950-5423 2024/04/07 [Refereed]
Summary Our previous study found that glycation with uronic acid‐type reducing sugar enhanced the anti‐inflammatory effect of fish myofibrillar protein (Mf) via the Maillard reaction, and the molecular mechanism of enhanced anti‐inflammatory effect was investigated in this study. Mf was glycated with various reducing sugars at 60 °C and 35% relative humidity. After pepsin‐trypsin digestion, the anti‐inflammatory effects were evaluated by assessing secretions of pro‐inflammatory cytokines and expressions of LPS‐stimulated signalling pathway‐related genes in RAW 264.7 macrophages. Mf glycated with uronic acid‐type reducing sugars: glucuronic acid, galacturonic acid and alginate oligosaccharide, suppressed expression of cd14 and further suppressed expressions of tlr4 and myd88 comparing with intact and glycated Mf with glucose and galactose. Furthermore, uronic acid‐glycated Mf significantly suppressed expressions and secretions of pro‐inflammatory cytokines. The results indicate that uronic acid‐type glycation enhances anti‐inflammatory effect of Mf by attenuating expression of cd14 and enhancing the Mf‐induced suppression in TLR4‐MyD88‐dependent inflammatory signalling pathway. - Yutaka Shimizu, Ga-hyun Joe, Hiroki SaekiFisheries Science 0919-9268 2024/03/08 [Refereed]
- Boxue Yang, Wenzhao Li, Hiroki Saeki, Yutaka Shimizu, Ga-Hyun JoeFood & Function 2042-6496 2024/02 [Refereed][Not invited]
18h AO-glycated collagen (C-AO) reduced LPS receptor expression, enhancing anti-inflammatory and anti-oxidant effects in macrophages. C-AO shows potential in disease prevention and inflammation management. - Ulfah Amalia, Yutaka Shimizu, Ga-Hyun Joe, Hiroki SaekiFood Chemistry 434 137491 - 137491 0308-8146 2024/02 [Refereed]
- Masataka Ono, Satomi Watari, Mizuho Nishizawa-Higashi, Tatsuya Konishi, Yoshinori Takahashi, Hiroki Saeki, Ga-Hyun JoeFood Chemistry: Molecular Sciences 6 100165 - 100165 2666-5662 2023/07 [Refereed]
- Wenzhao Li, Boxue Yang, Ga-Hyun Joe, Yutaka Shimizu, Hiroki SaekiFood Chemistry 407 135162 - 135162 0308-8146 2023/05 [Refereed]
- Ga-Hyun Joe, Masafumi Masuoka, Ryosuke Reisen, Seiya Tanaka, Hiroki SaekiMarine Drugs 21 (5) 276 - 276 2023/04/28 [Refereed]
A separation process was established to sequentially fractionate and recover three anti-inflammatory components derived from sugars, phycobiliprotein, and chlorophyll from the hot-air-dried thalli of the red alga dulse (Palmaria palmata). The developed process consisted of three steps, without the use of organic solvents. In Step I, the sugars were separated by disrupting the cell wall of the dried thalli with a polysaccharide-degrading enzyme, and a sugar-rich extract (E1) was obtained by precipitating the other components, which were simultaneously eluted by acid precipitation. In Step II, the residue suspension from Step I was digested with thermolysin to obtain phycobiliprotein-derived peptides (PPs), and a PP-rich extract (E2) was obtained by separating the other extracts using acid precipitation. In Step III, solubilized chlorophyll was obtained by heating the residue, which was acid-precipitated, neutralized, and re-dissolved to concentrate the chlorophyll-related components (Chls)-rich extract (E3). These three extracts suppressed inflammatory-cytokine secretion by lipopolysaccharide (LPS)-stimulated macrophages, confirming that the sequential procedure had no negative effects on the activities of any of the extracts. The E1, E2, and E3 were rich in sugars, PPs, and Chls, respectively, indicating that the anti-inflammatory components were effectively fractionated and recovered through the separation protocol. - Boxue Yang, Wenzhao Li, Asuka Ishii, Ga-hyun Joe, Yutaka Shimizu, Yasuaki Takagi, Hiroki SaekiWaste and Biomass Valorization 1877-2641 2023/03/24 [Refereed]
- Ulfah Amalia, Yutaka Shimizu, Ga-Hyun Joe, Hiroki SaekiFisheries Science 0919-9268 2023/01/18 [Refereed]
- Tomoko Shimoda, Hidehisa Shimizu, Wakana Iwasaki, Hongxia Liu, Yoshie Kamo, Koji Tada, Taketo Hanai, Shota Hori, Ga-Hyun Joe, Yasutake Tanaka, Masao Sato, Hitoshi Miyazaki, Satoshi IshizukaBioscience, Biotechnology, and Biochemistry 87 (4) 434 - 441 0916-8451 2023/01/09 [Refereed]
Abstract A diet supplemented with cholic acid (CA), the primary 12α-hydroxylated bile acid, can induce hepatic lipid accumulation in rats without obesity. This study examined the effects of a CA-supplemented diet on blood pressure (BP). After acclimation, WKAH/HkmSlc rats (3 week old) were divided into two groups and fed with a control AIN-93-based diet or a CA-supplemented diet (0.5 g CA/kg) for 13 weeks. The CA diet increased systolic and diastolic BP as well as hepatic lipid concentrations in the rats. No changes were found in the blood sodium concentration. Urinary albumin concentration increased in CA-fed rats. An increase was observed in the hepatic expression of ATP binding cassette subfamily B member 1B that correlated BPs and urinary albumin concentration accompanied by an increase in portal taurocholic acid concentration. These results suggest that 12α-hydroxylated bile acids are involved in increased BP and albuminuria via alteration of hepatic function. - Boxue Yang, Ga-Hyun Joe, Wenzhao Li, Yutaka Shimizu, Hiroki SaekiFoods 11 (15) 2374 - 2374 2022/08/08 [Refereed]
To improve the antioxidant activity of collagen molecules using Maillard-type glycation, the relation between antioxidant activity and progress indexes for the Maillard reaction must be understood. In this study, lyophilized tilapia scale collagen was mixed with a half weight of alginate oligosaccharide (AO) or glucose and incubated at 60 °C and 35% relative humidity for up to 18 h to produce the Maillard-type glycated collagen (C-AO and C-Glu, respectively). As glycation progressed, the amount of conjugated sugar coupled with UV-vis absorbance at 294 nm and 420 nm increased more rapidly in C-Glu than in C-AO, and the available lysine decreased rapidly in C-Glu compared with C-AO. The early-to-middle- and late-stage products of the Maillard reaction were involved in enhanced antioxidant activity of digested C-AO and digested C-Glu, respectively. Additionally, C-AO acquired the antioxidant activity without marked available lysine loss. The cytoprotective effect of collagen in H2O2-induced damage was enhanced by glycation, achieved by reducing malondialdehyde content and increasing superoxide dismutase and catalase activities. These results indicate that AO is an excellent reducing sugar that enhances the health benefits of collagen without excessive loss of lysine, which is a nutritional problem of the Maillard-type glycation. - Daichi Sugita, Ga-Hyun Joe, Masafumi Masuoka, Yasuyuki Konishi, Hiroki SaekiFisheries Science 0919-9268 2022/07/20 [Refereed]
- Yeonmi Lee, Yasutake Tanaka, Wakana Iwasaki, Fumika Yokoyama, Ga-Hyun Joe, Misaki Tsuji, Takuma Nose, Koji Tada, Taketo Hanai, Shota Hori, Hidehisa Shimizu, Kimiko Minamida, Kazunori Miwa, Satoshi IshizukaJournal of Functional Foods 90 104991 - 104991 1756-4646 2022/03 [Refereed]
A dietary symbiotic supplement of okara, a by-product of tofu manufacturing with Bacillus coagulans lilac-01 found to reduce secondary bile acid (BA) in a rat study and cholic acid (CA), a primary 12α-hydroxylated (12αOH) BA, induces lipid accumulation in rats. In this study, we investigated whether dietary supplementation of a synbiotic with okara and Bacillus coagulans lilac-01 improves CA-induced hepatic lipid accumulation. Male Wistar/ST rats (4 weeks old) were fed with or without CA-supplementation combined with the synbiotic for 2 weeks. The CA diet increased hepatic triglycerides and the synbiotic diet in combination with CA normalized liver triglyceride concentration accompanied by suppression of hepatic fatty acid synthase expression, enhancement of fecal triglyceride excretion, and increase in fecal non-12αOH BA excretion. Dietary supplementation with the okara synbiotic ameliorated hepatic lipid accumulation probably by reducing de novo lipogenesis and enhancing fecal triglyceride excretion. - Ga-Hyun Joe, Masataka Ono, Koji Tsuji, Tadaaki Takeda, Hiroki SaekiFisheries Science 0919-9268 2021/07/12 [Refereed]
- Reika Yoshitsugu, Hongxia Liu, Yoshie Kamo, Akari Takeuchi, Ga-Hyun Joe, Koji Tada, Keidai Kikuchi, Nobuyuki Fujii, Shinri Kitta, Shota Hori, Manami Takatsuki, Hitoshi Iwaya, Yasutake Tanaka, Hidehisa Shimizu, Satoshi IshizukaScientific Reports 11 (1) 12939 - 12939 2021/06/21 [Refereed]
Abstract We previously reported that dietary supplementation with cholic acid (CA), the primary 12α-hydroxylated (12αOH) bile acid (BA), reduces plasma adiponectin concentration in rats. The aim of this study was to examine the distribution of adiponectin in the body of CA-fed rats and its influence on mucosal immunoglobulin A concentration in the intestine. Rats were fed a diet supplemented with or without CA (0.5 g CA/kg diet) for 13 weeks. A reduction in plasma adiponectin level was observed from week 3. At the end of the experiment, the CA diet reduced plasma adiponectin concentration both in the portal and aortic plasma. Accumulation of adiponectin was accompanied by an increase in cadherin-13 mRNA expression in the ileal mucosa of CA-fed rats. No increase was observed in adiponectin mRNA expression in the ileal and adipose tissues of the CA-fed rats. Immunoglobulin A concentration in the ileal mucosa was elevated in the CA-fed rats and was correlated with the ileal adiponectin concentration. 12αOH BAs may modulate mucosal immune response that are involved in the accumulation of adiponectin in the ileum. - Kunichika Sugihara, Mizuho Nishizawa-Higashi, Ga-Hyun Joe, Yutaka Onishi, Yutaka Shimizu, Hiroki SaekiFisheries Science 87 (4) 569 - 577 0919-9268 2021/04/26 [Refereed]
- Ja-Young Lee, Hidehisa Shimizu, Masahito Hagio, Satoru Fukiya, Masamichi Watanabe, Yasutake Tanaka, Ga-Hyun Joe, Hitoshi Iwaya, Reika Yoshitsugu, Keidai Kikuchi, Misaki Tsuji, Nanako Baba, Takuma Nose, Koji Tada, Taketo Hanai, Shota Hori, Akari Takeuchi, Yumiko Furukawa, Bungo Shirouchi, Masao Sato, Tadasuke Ooka, Yoshitoshi Ogura, Tetsuya Hayashi, Atsushi Yokota, Satoshi IshizukaBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1865 (12) 158811 - 158811 1388-1981 2020/12 [Refereed]
© 2020 The Authors There is an increasing need to explore the mechanism of the progression of non-alcoholic fatty liver disease. Steroid metabolism is closely linked to hepatic steatosis and steroids are excreted as bile acids (BAs). Here, we demonstrated that feeding WKAH/HkmSlc inbred rats a diet supplemented with cholic acid (CA) at 0.5 g/kg for 13 weeks induced simple steatosis without obesity. Liver triglyceride and cholesterol levels were increased accompanied by mild elevation of aminotransferase activities. There were no signs of inflammation, insulin resistance, oxidative stress, or fibrosis. CA supplementation increased levels of CA and taurocholic acid (TCA) in enterohepatic circulation and deoxycholic acid (DCA) levels in cecum with an increased ratio of 12α-hydroxylated BAs to non-12α-hydroxylated BAs. Analyses of hepatic gene expression revealed no apparent feedback control of BA and cholesterol biosynthesis. CA feeding induced dysbiosis in cecal microbiota with enrichment of DCA producers, which underlines the increased cecal DCA levels. The mechanism of steatosis was increased expression of Srebp1 (positive regulator of liver lipogenesis) through activation of the liver X receptor by increased oxysterols in the CA-fed rats, especially 4β-hydroxycholesterol (4βOH) formed by upregulated expression of hepatic Cyp3a2, responsible for 4βOH formation. Multiple regression analyses identified portal TCA and cecal DCA as positive predictors for liver 4βOH levels. The possible mechanisms linking these predictors and upregulated expression of Cyp3a2 are discussed. Overall, our observations highlight the role of 12α-hydroxylated BAs in triggering liver lipogenesis and allow us to explore the mechanisms of hepatic steatosis onset, focusing on cholesterol and BA metabolism. - Tomoko Shimoda, Shota Hori, Kenta Maegawa, Akari Takeuchi, Yeonmi Lee, Ga-Hyun Joe, Yasutake Tanaka, Hidehisa Shimizu, Satoshi IshizukaLipids in health and disease 19 (1) 137 - 137 2020/06/16 [Refereed][Not invited]
BACKGROUND: Inbred strains are characterized by less genetic variation, which suggests usefulness of inbred strains for evaluations of various parameters. In this study, experimental reproducibility in several parameters was compared between an outbred Wistar rat and Wistar King A Hokkaido (WKAH/HkmSlc) rat, the inbred strain that is originated from Wistar rats. METHODS: Difference of variations was investigated in parameters of body compositions and liver functions such as body weight, liver weight, liver triglycerides (TG), liver cholesterol and plasma alanine aminotransferase activity (ALT) between WKAH rats and outbred Wistar rats by using the coefficient of variation (CV). RESULTS: There was no difference in the CVs of body weight and relative liver weight between WKAH and Wistar rats. The CVs of body weight and relative liver weight were below 10% in both WKAH and Wistar rats. The CVs of TG, cholesterol, and ALT in Wistar rats were between 30 and 40%, whereas those in WKAH rats were between 10 and 25%. A low CV level of TG was observed in WKAH rats compared to that in Wistar rats regardless of the duration of the experimental period in those rat strains. CONCLUSION: The low CV values in metabolic parameters involved in liver functions in the inbred rats suggested an advantage of using inbred rather than outbred rats for the evaluation of liver lipid metabolism. - Yeonmi Lee, Reika Yoshitsugu, Keidai Kikuchi, Ga-Hyun Joe, Misaki Tsuji, Takuma Nose, Hidehisa Shimizu, Hiroshi Hara, Kimiko Minamida, Kazunori Miwa, Satoshi IshizukaBRITISH JOURNAL OF NUTRITION 116 (4) 603 - 610 0007-1145 2016/08 [Refereed][Not invited]
Intestinal bacteria are involved in bile acid (BA) deconjugation and/ or dehydroxylation and are responsible for the production of secondary BA. However, an increase in the production of secondary BA modulates the intestinal microbiota due to the bactericidal effects and promotes cancer risk in the liver and colon. The ingestion of Bacillus coagulans improves constipation via the activation of bowel movement to promote defaecation in humans, which may alter BA metabolism in the intestinal contents. BA secretion is promoted with high-fat diet consumption, and the ratio of cholic acid (CA): chenodeoxycholic acid in primary BA increases with ageing. The dietary supplementation of CA mimics the BA environment in diet-induced obesity and ageing. We investigated whether B. coagulans lilac-01 and soya pulp influence both BA metabolism and the maintenance of host health in CA-supplemented diet-fed rats. In CA-fed rats, soya pulp significantly increased the production of secondary BA such as deoxycholic acid and omega-muricholic acids, and soya pulp ingestion alleviated problems related to plasma adiponectin and gut permeability in rats fed the CA diet. The combination of B. coagulans and soya pulp successfully suppressed the increased production of secondary BA in CA-fed rats compared with soya pulp itself, without impairing the beneficial effects of soya pulp ingestion. In conclusion, it is possible that a combination of prebiotics and probiotics can be used to avoid an unnecessary increase in the production of secondary BA in the large intestine without impairing the beneficial functions of prebiotics. - Ga-Hyun Joe, Midori Andoh, Aki Shinoki, Weeranuch Lang, Yuya Kumagai, Juri Sadahiro, Masayuki Okuyama, Atsuo Kimura, Hidehisa Shimizu, Hiroshi Hara, Satoshi IshizukaBIOMEDICAL RESEARCH-TOKYO 37 (3) 179 - 186 0388-6107 2016 [Refereed][Not invited]
The term "megalo-saccharide" is used for saccharides with ten or more saccharide units, whereas the term "oligo-saccharide" is used for saccharides containing fewer than ten monosaccharide units. Megalo-type alpha-1,6-glucosaccharide (M-IM) is a non-digestible saccharide and not utilized by intestinal bacteria, suggesting that ingested M-IM may encounter ileum Peyer's patches that contains immune cells such as macrophages. Macrophages are responsible for antigen incorporation and presentation during the initial step of immune responses. We investigated whether M-IMs modulate macrophage functions such as cytokine production, nitric oxide production, cell viability, and phagocytosis. Primary macrophages collected from the rats were cultured with the existence of M-IM or lipopolysaccharides (LPS). M-IM and LPS induced the production of tumor necrosis factor alpha (TNF alpha), interleukin 6 (IL6), and nitric oxide in the primary macrophages. The gene expression profile of inflammatory factors including TNF alpha, IL6, and IL1 beta in M-IM-stimulated cells was similar to that of LPS-stimulated cells. The M-IM did not affect phagocytosis in the primary macrophages. The M-IM-induced TNF alpha production was suppressed in the cells treated with a toll-like receptor 4 (TLR4) inhibitor called TAK-242. In conclusion, the M-IM modulates cytokine expression via TLR4 signaling and may play a role in the modulation of immune responses. - Hidehisa Shimizu, Nanako Baba, Takuma Nose, Ryoko Taguchi, Shinya Tanaka, Ga-Hyun Joe, Hideaki Maseda, Nobuhiko Nomura, Masahito Hagio, Ja-Young Lee, Satoru Fukiya, Atsushi Yokota, Satoshi Ishizuka, Hitoshi MiyazakiBIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 79 (6) 937 - 942 0916-8451 2015/06 [Refereed][Not invited]
The signal molecule, 3-oxo-C-12-homoserine lactone (3-oxo-C-12-HSL), is similar to a mammalian hormone in bacteria. Although most studies have examined the effects of high 3-oxo-C-12-HSL concentrations (>200 mu M) on mammalian cellular functions because ~600 mu M 3-oxo-C-12-HSL can be secreted in biofilms of Pseudomonas aeruginosa grown in vitro, we previously showed that a low 3-oxo-C-12-HSL concentration (30 mu M) induces the apoptosis of undifferentiated Caco-2 cells through suppressing Akt activity. Here, we found that a low concentration of 3-oxo-C-12-HSL-activated ERK1/2 in undifferentiated Caco-2 cells. Incubating cells with the ERK pathway inhibitor U0126 for 30min alleviated the mucin 3 (MUC3) expression suppressed by 3-oxo-C-12-HSL, and the upregulation of MUC3 expression induced by a 48-h incubation with U0126-reduced cell death. Thus, altered MUC3 expression caused by long-term attenuated ERK1/2 activity might correlate with the death of undifferentiated Caco-2 cells induced by 3-oxo-C-12-HSL. - Masahito Hagio, Hidehisa Shimizu, Ga-Hyun Joe, Manami Takatsuki, Maiko Shiwaku, Hong Xu, Ja-Young Lee, Nobuyuki Fujii, Satoru Fukiya, Hiroshi Hara, Atsushi Yokota, Satoshi IshizukaTOXICOLOGY LETTERS 232 (1) 246 - 252 0378-4274 2015/01 [Refereed][Not invited]
Consumption of a high-fat diet increases some secondary bile acids (BAs) such as deoxycholic acid (DCA) in feces. DCA is derived from cholic acid (CA), a primary BA. We evaluated intestinal epithelial proliferation and BA metabolism in response to oral administration of cholic acid (CA) in rats to determine the influence of a CA diet on the responses of gut epithelia to gamma-rays. WKAH/HkmSlc rats were divided into two dietary groups: control diet or CA-supplemented (2 g/kg diet) diet. Some of the rats from each group were irradiated with gamma-rays, and epithelial cell proliferation in the colon was analyzed histochemically. Unirradiated CA-fed rats had high levels of DCA and CA in the sera, as well as the presence of taurocholic acid in their feces. Significant increases were observed in both epithelial proliferation and the number of epithelial cells in the colon of the CA-fed rats, and this effect was observed at 8 weeks after gamma-ray exposure. Furthermore, extracts from both cecal contents and sera of the unirradiated CA-fed rats promoted proliferation of IEC-6 cells. These results indicate that BAs in enterohepatic circulation promote proliferation and survival of the intestinal epithelium after receiving DNA damage. (C) 2014 Elsevier Ireland Ltd. All rights reserved. - Ryoko Taguchi, Shinya Tanaka, Ga-Hyun Joe, Hideaki Maseda, Nobuhiko Nomura, Junji Ohnishi, Satoshi Ishizuka, Hidehisa Shimizu, Hitoshi MiyazakiAMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY 307 (2) C162 - C168 0363-6143 2014/07 [Refereed][Not invited]
N-acyl-homoserine lactones (AHL) are quorum-sensing molecules in bacteria that play important roles in regulating virulence gene expression in pathogens such as Pseudomonas aeruginosa. The present study compared responses between undifferentiated and differentiated Caco-2 cells to N-(3-oxododecanoyl)- L-homoserine lactone (3-oxo-C-12-HSL). A low concentration of 3-oxo-C-12-HSL (30 mu M) is sufficient to reduce viability accompanied by apoptosis via the suppression of phosphorylation by Akt in undifferentiated Caco-2 cells. The suppression of Akt phosphorylation appears specific in 3-oxo-C-12-HSL, because other AHLs did not influence the phosphorylation status of Akt. The reduced viability induced by 3-oxo-C-12-HSL was partially recovered by constitutively active Akt overexpression in undifferentiated Caco-2 cells. Since mucin is considered a vital component of the gut barrier, we investigated whether mucin protects cellular functions induced by 3-oxo-C-12-HSL in undifferentiated Caco-2 cells. The results showed that mucin protected undifferentiated Caco-2 cells from apoptosis induced by 3-oxo-C-12-HSL. 3-Oxo-C-12-HSL did not induce cell death in differentiated Caco-2 cells that expressed higher levels of mucin 3 (MUC3) than undifferentiated Caco-2 cells. In addition, 3-oxo-C-12-HSL promoted cell death in undifferentiated Caco-2 cells transfected with MUC3 siRNA and reduced MUC3 expression in undifferentiated Caco-2 cells. Therefore, MUC3 might be responsible for the survival of undifferentiated intestinal epithelial cells in the presence of 3-oxo-C-12-HSL through regulating Akt phosphorylation. In conclusion, 3-oxo-C-12-HSL might influence the survival of undifferentiated intestinal epithelial cells as well as interactions between these cells and pathogens. - Ga-Hyun Joe, Midori Andoh, Mikako Nomura, Hitoshi Iwaya, Jae-Sung Lee, Hidehisa Shimizu, Youhei Tsuji, Hideaki Maseda, Hitoshi Miyazaki, Hiroshi Hara, Satoshi IshizukaBIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY 78 (3) 462 - 465 0916-8451 2014 [Refereed][Not invited]
We investigated to determine whether a variety of acyl-homoserine lactones (AHLs) influences epithelial cell proliferation and mucosal permeability. 3-Oxo-C-12-homoserine lactone (HSL) and 3-oxo-C-14-HSL significantly suppressed IEC-6 cell proliferation. A significant increase in mucosal permeability was observed in isolated rat colon tissue exposed to C-12-HSL, 3-oxo-C-12-HSL, and 3-oxo-C-14-HSL. These data indicate that AHLs suppress epithelial proliferation and disrupt barrier function in intestinal mucosa.
MISC
- Ga-Hyun Joe, Takahisa Iizuka, Yoshinori Fujimoto, Atsuo Kimura, Hiroshi Hara, Satoshi Ishizuka FASEB JOURNAL 31- 2017/04 [Not refereed][Not invited]
- 高橋勇太郎, LEE Dongguen, LEE Yeonmi, JOE Gahyun, 加茂佳恵, 多田幸司, 堀将太, 花井健人, 竹内あかり, 田中愛健, 清水英寿, 若松純一, 原博, 石塚敏, 玖村朗人 日本農芸化学会大会講演要旨集(Web) 2017- ROMBUNNO.2A08a08 (WEB ONLY) 2017/03/05 [Not refereed][Not invited]
- Ga-Hyun Joe, Shota Hori, Hidehisa Shimizu, Hiroshi Hara, Satoshi Ishizuka FASEB JOURNAL 30- 2016/04 [Not refereed][Not invited]
- Hidehisa Shimizu, Masahito Hagio, Reika Yoshitsugu, Keidai Kikuchi, Ga Hyun Joe, Hiroshi Hara, Satoshi Ishizuka FASEB JOURNAL 27- 2013/04 [Not refereed][Not invited]
- Satoshi Ishizuka, Manami Takatsuki, Maiko Shiwaku, Masahito Hagio, Reika Yoshitsugu, Keidai Kikuchi, Nobuyuki Fujii, Ga‐Hyun Joe, Hidehisa Shimizu, Hiroshi Hara, Satoru Fukiya, Atsushi Yokota The FASEB Journal 27- (S1) 2013/04 [Not refereed][Not invited]
Bile acid (BA) increases in feces under consumption of high‐fat and high‐sucrose diet and some BAs, such as deoxycholic acid (DCA), have strong antibiotic activity. We evaluated bile acid metabolism, serum biochemical parameters, epithelial proliferation, as well as cecal microbiota in response to oral administration of cholic acid (CA) in rats. WKAH/HkmSlc rats (3‐ week‐old, male) were divided into two dietary groups, such as control group fed an AIN‐93 based diet or CA (0.2g/kg diet)‐ containing diet for 10 days. Some of the rats were irradiated with gamma‐rays (0.65 Gy/min, 60Co) at the end of the dietary intervention. We measured BA concentration in the sera, bile, and feces in an unirradiated condition by using UPLC/ESI‐MS. In CA–fed rats, a large amount of DCA and CA are found in the sera and taurocholic acid was also detected in the feces. Cecal microbita were determined with 16S rRNA clone library method. In the gut microbiota, population of Firmicutes was beyond 90% in the CA‐fed rats. There was a significant increase in epithelial proliferation assessed by bromodeoxyuridine‐incorporation in CA‐fed rats even after exposure to gamma‐rays. These results indicate that BA is a factor regulating the gut microbiota as well as epithelial proliferation. This work is supported by Regional Innovation Strategy Support Program of the MEXT, The Japanese Government.
Presentations
- 未利用・廃棄水産資源の活用と SDGs への 貢献Ga-Hyun Joe未利用資源活用セミナー 畜産・水産物における未利用資源活用の取り組み 2023/03
- Increased PTH secretion and Ca absorption rate due to fish bone intake in ratsGa-Hyun JOE, Kazuki FUJIMOTO, Hirofumi TAKEDA, Hiroki SAEKI22nd IUNS-ICN International Congress of Nutrition in Tokyo, Japan 2022/12
- 健康機能から見た未利用・廃棄水産資源の高度利用Ga-Hyun Joe日本栄養·食糧学会 北海道支部 シンポジウム「北海道におけるこれからの栄養・食糧学」 2022/03
- 熱風乾燥した紅藻ダルスに含まれる各種抗炎症成分の個別抽出法の開発 [Not invited]増岡 雅文,岸 夏海,趙 佳賢,清水 裕,佐伯 宏樹,第73回日本栄養・食糧学会大会 2019/05
- アルギン酸オリゴ糖修飾したシロザケ筋肉ペプチド間における抗炎症作用の比較大西 豊, 李, 趙 佳賢, 佐伯 宏樹日本栄養・食糧学会北海道・東北合同支部大会および公開シンポジウム 2018/11
- 熱風乾燥ダルスのプロテアーゼ処理条件が各種抗炎症成分の抽出挙動に及ぼす影響 [Not invited]岸 夏海,増岡 雅文,趙 佳賢,清水 裕,佐伯 宏樹日本栄養・食糧学会北海道・東北合同支部大会および公開シンポジウム 2018/11
- 熱風乾燥した紅藻ダルスからの抗炎症成分の効率的な抽出法の開発 [Not invited]増岡 雅文,岸 夏海,趙 佳賢,清水 裕,佐伯 宏樹日本栄養・食糧学会北海道・東北合同支部大会および公開シンポジウム 2018/11
- Ingestion of skim milk cheese modulates bile acid metabolism and cholic acid-induced disorders in rats. [Not invited]GA-HYUN JOEThe International Conference of Korean Society of Food Science of Animal Resources and 49th Annual Meeting 2017/05
- Ingestion of megalo-type isomaltoglucosaccharides ameliorates lipopolysaccharide-induced acute liver injury in rats. [Not invited]GA-HYUN JOEExperimental Biology 2017/04
- 胆汁酸摂取ラット回腸粘膜におけるIgA産生の増加 [Not invited]趙 佳賢日本農芸化学会2017年度大会（京都） 2017/03
- 胆汁酸誘導性未病状態の脱脂乳チーズによる改善作用 [Not invited]趙 佳賢日本農芸化学会2017年度大会（京都） 2017/03
- 胆汁酸誘導性病態の発症に及ぼす脱脂乳チーズ摂取の作用 [Not invited]趙 佳賢日本農芸化学会北海道支部平成28年度第1回講演会（函館） 2016/08
- Cholic acid promotes gut epithelial proliferation in rats exposed to gamma-radiation. [Not invited]GA-HYUN JOEXXIV International Bile Acid Meeting: Bile Acids in Health and Disease, Düsseldorf, Germany 2016/06
- A reduction of myeloperoxidase and interleukin-10 expressions in mesenteric lymphnodes of the rats fed a cholic acid-supplemented diet. [Not invited]GA-HYUN JOEExperimental Biology 2016/04
- A diet supplemented with cholic acid induced hepatic steatosis without apparent inflammation and reduced myeloperoxidase and interleukin-10 expressions in the mesenteric lymph nodes in rats. [Not invited]GA-HYUN JOE第21回Hindgut Club Japanミーティング（東京） 2015/12
- Isomaltomegalosaccharides modulation rat macrophage functions in primary culture and cytokine expression in rat intestinal mucosa. [Not invited]GA-HYUN JOEThe 6th International Conference on Food Factors 2015/11
- Modulation of rat macrophage functions by isomaltomegalosaccharides. [Not invited]GA-HYUN JOE12th Asian Congress of Nutrition 2015/05
- Modulation of immune-related gene expressions in mesenteric lymph nodes of the rats fed cholic acid-supplemented diet. [Not invited]GA-HYUN JOE日本農芸化学会大会（岡山） 2015/03
- Deoxycholic acid is involved in the initiation and progression of atherosclerosis [Not invited]GA-HYUN JOEExperimental Biology 2013 2014/04
- Ingestion of cholic acid modulates the gut microbiota and intestinal epithelial proliferation. [Not invited]GA-HYUN JOEObesity Week 2013 2013/11
- Evaluation of isolation and culture procedure for sodium periodate-induced peritoneal elicited cells as a model system of functional analysis in primary macrophages. [Not invited]GA-HYUN JOE日本農芸化学会北海道支部夏期シンポジウム（旭川） 2013/08
- Cytokine production in immune cells in response to megalo type isomaltosylglucosaccharides [Not invited]GA-HYUN JOE日本栄養・食糧学会第67回大会（名古屋） 2013/05
- Supplementation of cholic acid in enterohepatic circulation modulates the gut microbiota and epithelial proliferation. [Not invited]GA-HYUN JOEExperimental Biology 2013 2013/04
- TNFα production in mesenteric leukocytes and Raw 264.7 cells in response to megalo type isomaltosylglucosaccharides. [Not invited]GA-HYUN JOE第18回Hindgut Club Japanミーティング（東京） 2012/12
- 10. Carboxyl group in reducing sugar is an important factor for enhancing anti-inflammatory activity of glycated fish myofibrillar protein令和3年度公益社団法人日本水産学会春季大会
- Carboxyl group in reducing sugar is an important factor for enhancing anti-inflammatory activity of glycated fish myofibrillar protein令和3年度公益社団法人日本水産学会春季大会
Association Memberships
- THE JAPANESE SOCIETY OF FISHERIES SCIENCE JAPAN SOCIETY OF NUTRITION AND FOOD SCIENCE JAPAN SOCIETY FOR BIOSCIENCE
Research Projects
- Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)Date (from‐to) : 2021/04 -2024/03Author : 佐伯 宏樹, 趙 佳賢2021年度は，抗炎症機能の詳細な検証・メカニズム解析と，機能タンパク質の特定を計画していたが，利用予定していた分析装置の入手の遅れから，メカニズム解析は追試験のレベルに留まった。そのため，2021ー22年に予定していた水溶性タンパク質画分（WSP）の組成分析を先行実施するとともに，凍結筋肉や工場廃水からWSPを抽出し，抗炎症機能の差異を検討し,WSPのもつ抗炎症機能の安定性を検証した。さらに2022年度の動物実験を踏まえて，メイラード反応を用いた糖鎖導入が，その抗炎症作用におよぼす影響を調査した。 まず，スケトウダラ筋肉の水抽出画分から，等電点沈殿を主体とした生化学的手法によってWSPを調製し，これを電気泳動分画，免疫染色，TOF-MS分析に供して，含有成分の特定をおこなったところ，（1）WSPは解糖系酵素群，ミオシン軽鎖，およびパルブアルブミンから成ることを確認した。続いて（2）スケトウダラの生鮮筋肉，凍結筋肉，さらに冷凍すりみ工場の工場廃液のいずれを原料としても，各WSPはLPS刺激したマウスマクロファージの炎症性サイトカイン産生を抑制した。さらに(3)糖鎖導入はWSPの抗炎症機能を増強することを明らかにできた。 (1)と(2)の結果は，WSPの構成タンパク質との抗炎症機能が原材料の相違によらず維持されていることを示す結果であり，今後，本研究の知見を産業的に展開する上で重要な知見である。また（3）はメイラード反応による糖鎖導入が抗炎症機能を強く増強させる可能性を示した結果であり，2022年度の動物実験計画に反映させることで，本研究の意義を大いに高められる可能性がある。
- Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career ScientistsDate (from‐to) : 2021/04 -2024/03Author : 趙 佳賢周りを海に囲まれた日本では, 多様な水産資源を食品や加工品として利用しているが, それでも利用されていない水産資源もまだ多く存在する。暖流と寒流の双方の影響を受ける日本沿岸の岩礁域には多様な海藻が生息しているため, その資源量は豊富であるが, 食用種はわずかであり, 代表的な未利用水産資源である。本研究で対象とした未利用紅藻，ダルス (Palmaria palmata)の資源量は，函館市臼尻近郊だけでも，年間数千トンに到達すると推定されている。しかし，コンブ養殖の種苗ロープに繁茂して日光を遮断するため，そのほとんどが除去・廃棄されている。先行研究では，凍結乾燥ダルスに含まれる複数種の抗炎症成分であるフィコビリタンパク質由来ペプチド (PP) とクロロフィルa関連化合物 (Chls)の有効性の可能性が示唆された。 2021年度には，海藻の代表的な加工処理法である熱風乾燥を用いて，ダルスを熱風乾燥により減容化した藻体から，三つの有効成分(糖画分とPP画分，Chls画分)の分画抽出する方法を検討した。さらに，ダルス由来の有効成分が生活習慣病の発症・増悪に深く関与しているマクロファージの免疫応答におよぼす影響を調べた。その結果，未利用水産資源である紅藻ダルスから抽出したPP画分とChls画分が抗炎症効果を持ち，また両画分の作用メカニズムが異なることを明らかにした。まず(1)PP画分は免疫細胞を活性化させ，炎症の早期収束に寄与することで炎症を抑制する。次に(2)Chls画分はLPS受容体をはじめとする異物認識機能を調節することで，炎症を抑制する。このような研究成果はダルス由来のPP画分とChls画分が炎症抑制の機能性食品素材としての利用可能性が高いことを示唆する。
- 未利用紅藻・ダルスからの抗炎症糖質の効果的抽出と機能解析公益財団法人飯島藤十郎記念食品科学振興財団：令和３年度研究助成金Date (from‐to) : 2021/04 -2022/03
- 紅藻ダルスに含まれる免疫機能増強成分の活用公益財団法人北水協会：研究助成金Date (from‐to) : 2020/04 -2021/03
- Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research Grant-in-Aid for JSPS FellowsDate (from‐to) : 2016/04 -2018/03Author : 趙 佳賢先行の研究で一次胆汁酸であるコール酸の摂取が脂肪肝を誘導し、未病モデルであることを見出した。この病態モデルでの脂肪肝は1st hit直後の状態で、2nd hit前の単純性脂肪肝であると考えられる。しかしながら、肝臓や血中での炎症反応は見られず、消化管透過性の亢進が確認された。そこで、コール酸負荷による脂肪肝発症メカニズムを調べるため、LPSを2nd hitしてコール酸摂取ラットに投与し、肝炎での悪化を調べた。コール酸を10週間摂取した Fischer344ラットにLPSを皮下に投与、投与6時間後に解剖を行った。その結果、先行研究においてWKAH系統のラットで見られた透過性の亢進は見られなかった。肝臓及び消化管内容物における胆汁酸組成が系統間で異なることより、消化管透過性に影響を及ぼすことが考えられる。一方で肝障害マーカーがコール酸群でさらに増加したことから、コール酸負荷が肝障害の悪化させることが明らかになった。また、そのメカニズムを調べるため、肝臓での炎症関連遺伝子や繊維化マーカの発現を分析した。しかし、LPS刺激でのコール酸摂取による炎症や繊維化関連遺伝子発現には有意差が見られなかった。LPSによる炎症反応に自然免疫細胞であるマクロファージが関与していることから、マクロファージの機能に関与する遺伝子を分析した結果、群間差は見られなかった。本研究では0.05％コール酸摂取による単純性脂肪肝の病態モデルで、LPS刺激による肝障害の悪化が示唆された。高脂肪食の摂取は胆汁酸の分泌を促進させ、加齢により一次胆汁酸であるコール酸の割合が増加する。また、高脂肪食による体内でのLPS濃度の増加や加齢による免疫システムの変化が知られている。したがって、胆汁酸摂取による単純性脂肪肝の発症が「未病」状態であることを強く示唆するだけでなく、炎症や代謝疾患の発症や悪化に繋がる可能性も示している。