• 제목/요약/키워드: Critical Pathways

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Mass spectrometry-based approaches to explore metabolism regulating ferroptosis

  • Nguyen, Chi Thi Ngoc;Kim, Seon Min;Kang, Yun Pyo
    • BMB Reports
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    • 제55권9호
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    • pp.413-416
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    • 2022
  • Ferroptosis is a type of programmed cell death distinct from apoptosis or necroptosis. Ferroptosis is well characterized by an iron-dependent accumulation of lipid peroxides and disruption of cellular membrane integrity. Many metabolic alterations can prevent or accelerate ferroptosis induction. Recent advances in analytical techniques of mass spectrometry have allowed high-throughput analysis of metabolites known to be critical for understanding ferroptosis regulatory metabolism. In this review, we introduce mass spectrometry-based analytical methods contributing to recent discovery of various metabolic pathways regulating ferroptosis, focusing on cysteine metabolism, antioxidant metabolism, and poly-unsaturated fatty acid metabolism.

Reframing Loss: Chinese Diaspora Identity in K. H. Lim's Written in Black

  • Hannah Ming Yit Ho
    • 수완나부미
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    • 제15권2호
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    • pp.131-152
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    • 2023
  • In analyzing the Chinese diaspora, this paper explores losses that are encountered within the family in the nation. It argues that increased social and spatial mobilities that contribute to losses can be reconfigured through the productive lens of supermobility, as Laurence J. C. Ma conceptualizes it. Supermobile identities are significant avenues to consider the way that losses traditionally associated with migration and assimilation are revisited in view of new flows of migration and identification. In examining K. H. Lim's debut novel Written in Black (2014), this study addresses pathways from debilitating losses to productive losses journeyed by the family from the child's perspective. It offers a critical analysis of the Anglophone Bruneian novel in terms of its exclusive portrayal of an ethnic Chinese family. Departing from a fixed notion of home as cultural and physical rootedness, it explores flexible identities that are tied to shifting concepts of belonging. Rather than a magnification of social and spatial losses, the analysis highlights the way that the literary imagination of ethnic Chinese in Brunei Darussalam accommodates progressive ideas of the agency and advancement of the Chinese diaspora as a supermobile community.

Dietary Transformation of Lipid in the Rumen Microbial Ecosystem

  • Kim, Eun Joong;Huws, Sharon A.;Lee, Michael R.F.;Scollan, Nigel D.
    • Asian-Australasian Journal of Animal Sciences
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    • 제22권9호
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    • pp.1341-1350
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    • 2009
  • Dietary lipids are rapidly hydrolysed and biohydrogenated in the rumen resulting in meat and milk characterised by a high content of saturated fatty acids and low polyunsaturated fatty acids (PUFA), which contributes to increases in the risk of diseases including cardiovascular disease and cancer. There has been considerable interest in altering the fatty acid composition of ruminant products with the overall aim of improving the long-term health of consumers. Metabolism of dietary lipids in the rumen (lipolysis and biohydrogenation) is a major critical control point in determining the fatty acid composition of ruminant lipids. Our understanding of the pathways involved and metabolically important intermediates has advanced considerably in recent years. Advances in molecular microbial technology based on 16S rRNA genes have helped to further advance our knowledge of the key organisms responsible for ruminal lipid transformation. Attention has focused on ruminal biohydrogenation of lipids in forages, plant oils and oilseeds, fish oil, marine algae and fat supplements as important dietary strategies which impact on fatty acid composition of ruminant lipids. Forages, such as grass and legumes, are rich in omega-3 PUFA and are a useful natural strategy in improving nutritional value of ruminant products. Specifically this review targets two key areas in relation to forages: i) what is the fate of the lipid-rich plant chloroplast in the rumen and ii) the role of the enzyme polyphenol oxidase in red clover as a natural plant-based protection mechanism of dietary lipids in the rumen. The review also addresses major pathways and micro-organisms involved in lipolysis and biohydrogenation.

Gene Expression Profiling of Liver and Mammary Tissues of Lactating Dairy Cows

  • Baik, M.;Etchebarne, B.E.;Bong, J.;VandeHaar, M.J.
    • Asian-Australasian Journal of Animal Sciences
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    • 제22권6호
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    • pp.871-884
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    • 2009
  • Gene expression profiling is a useful tool for identifying critical genes and pathways in metabolism. The objective of this study was to determine the major differences in the expression of genes associated with metabolism and metabolic regulation in liver and mammary tissues of lactating cows. We used the Michigan State University bovine metabolism (BMET) microarray; previously, we have designed a bovine metabolism-focused microarray containing known genes of metabolic interest using publicly available genomic internet database resources. This is a high-density array of 70mer oligonucleotides representing 2,349 bovine genes. The expression of 922 genes was different at p<0.05, and 398 genes (17%) were differentially expressed by two-fold or more with 222 higher in liver and 176 higher in mammary tissue. Gene ontology categories with a high percentage of genes more highly expressed in liver than mammary tissues included carbohydrate metabolism (glycolysis, glucoenogenesis, propanoate metabolism, butanoate metabolism, electron carrier and donor activity), lipid metabolism (fatty acid oxidation, chylomicron/lipid transport, bile acid metabolism, cholesterol metabolism, steroid metabolism, ketone body formation), and amino acid/nitrogen metabolism (amino acid biosynthetic process, amino acid catabolic process, urea cycle, and glutathione metabolic process). Categories with more genes highly expressed in mammary than liver tissue included amino acid and sugar transporters and MAPK, Wnt, and JAK-STAT signaling pathways. Real-time PCR analysis showed consistent results with those of microarray analysis for all 12 genes tested. In conclusion, microarray analyses clearly identified differential gene expression profiles between hepatic and mammary tissues that are consistent with the differences in metabolism of these two tissues. This study enables understanding of the molecular basis of metabolic adaptation of the liver and mammary gland during lactation in bovine species.

Immune Enhancement Effect of Asterias amurensis Fatty Acids through NF-κB and MAPK Pathways on RAW 264.7 Cells

  • Monmai, Chaiwat;Go, Seok Hyeon;Shin, Il-shik;You, SangGuan;Lee, Hyungjae;Kang, SeokBeom;Park, Woo Jung
    • Journal of Microbiology and Biotechnology
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    • 제28권3호
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    • pp.349-356
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    • 2018
  • Asterias amurensis is a marine organism that causes damage to the fishing industry worldwide; however, it has been considered a promising source of functional components. The present study aimed to investigate the immune-enhancing effects of fatty acids from three organs of A. amurensis on murine macrophages (RAW 264.7 cells). A. amurensis fatty acids boosted production of immune-associated factors such as nitric oxide (NO) and prostaglandin E2 in RAW 264.7 cells. A. amurensis fatty acids also enhanced the expression of critical immune-associated genes, including iNOS, $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6, as well as COX-2. Western blotting showed that A. amurensis fatty acids stimulated the $NF-{\kappa}B$ and MAPK pathways by phosphorylation of $NF-{\kappa}B$ p-65, p38, ERK1/2, and JNK. A. amurensis fatty acids from different tissues resulted in different levels of $NF-{\kappa}B$ and MAPK phosphorylation in RAW 264.7 cells. The results increase our understanding of how A. amurensis fatty acids boost immunity in a physiological system, as a potential functional material.

Triglyceride Up-regulates Expression of ABCG1 in PMA-induced THP-1 Macrophages Through Activation of JNK and p38 MAPK Pathways

  • Lim, Jaewon;Kim, Sung Hoon;Kang, Yeo Wool;Jung, Byung Chul;Kim, Hyun-Kyung;Lee, Juyeon;Lee, Dongsup;Rhee, Ki-Jong;Kim, Yoon Suk
    • 대한의생명과학회지
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    • 제20권4호
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    • pp.237-243
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    • 2014
  • Triglyceride (TG) can cause death of macrophages and formation of foam cells thereby increasing inflammation in atherosclerotic plaques. Accumulation of cholesterol in macrophages is another critical event that promotes development of inflammatory cardiovascular diseases. Several proteins are known to transport intracellular cholesterol outside of the cell and these proteins are thought to be protective against atherosclerosis pathogenesis. It is unknown whether TG can affect cholesterol efflux in macrophages. In the current study, we examined mRNA expression levels of genes that promote efflux of cholesterol (ABCA1, ABCG1 and SR-B1). We found that TG treated THP-1 macrophages exhibited an increase in ABCG1 expression in a dose- and time-dependent manner. In contrast, the expression of ABCA1 and SR-B1 remained unchanged. To identify cell signaling pathways that participate in up-regulation of ABCG1, THP-1 macrophages were treated with various cell signaling inhibitors. We found that inhibition of the JNK and p38 MAPK pathway completely abrogated up-regulation of ABCG1 whereas inhibition of MEK1 further enhanced ABCG1 expression in TG treated THP-1 macrophages. Also, TG induced phosphorylation of JNK and p38 MAPK in THP-1 macrophages. These results suggest that TG may potentially influence cholesterol efflux in macrophages.

Obesity and Obese-related Chronic Low-grade Inflammation in Promotion of Colorectal Cancer Development

  • Pietrzyk, Lukasz;Torres, Anna;Maciejewski, Ryszard;Torres, Kamil
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권10호
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    • pp.4161-4168
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    • 2015
  • Colorectal cancer (CRC) is a worldwide health problem, being the third most commonly detected cancer in males and the second in females. Rising CRC incidence trends are mainly regarded as a part of the rapid 'Westernization' of life-style and are associated with calorically excessive high-fat/low-fibre diet, consumption of refined products, lack of physical activity, and obesity. Most recent epidemiological and clinical investigations have consistently evidenced a significant relationship between obesity-driven inflammation in particular steps of colorectal cancer development, including initiation, promotion, progression, and metastasis. Inflammation in obesity occurs by several mechanisms. Roles of imbalanced metabolism (MetS), distinct immune cells, cytokines, and other immune mediators have been suggested in the inflammatory processes. Critical mechanisms are accounted to proinflammatory cytokines (e.g. IL-1, IL-6, IL-8) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$). These molecules are secreted by macrophages and are considered as major agents in the transition between acute and chronic inflammation and inflammation-related CRC. The second factor promoting the CRC development in obese individuals is altered adipokine concentrations (leptin and adiponectin). The role of leptin and adiponectin in cancer cell proliferation, invasion, and metastasis is attributable to the activation of several signal transduction pathways (JAK/STAT, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase (PI3K), mTOR, and 5'AMPK signaling pathways) and multiple dysregulation (COX-2 downregulation, mRNA expression).

Immunostimulatory Activities of Polysaccharides from Liquid Culture of Pine-Mushroom Tricholoma matsutake

  • Kim, Joo-Young;Byeon, Se-Eun;Lee, Yong-Gyu;Lee, Ji-Yeon;Park, Jong-Sun;Hong, Eock-Ki;Cho, Jae-Youl
    • Journal of Microbiology and Biotechnology
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    • 제18권1호
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    • pp.95-103
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    • 2008
  • Mushrooms are regarded as one of the well-known foods and biopharmaceutical materials with a great deal of interest. Polysaccharide ${\beta}$-glucan is the major component of mushrooms that displays various biological activities such as antidiabetic, anticancer, and antihyperlipidemic effects. In this study, we compared the immunostimulatory potency of polysaccharide fractions, prepared from liquid culture of pine-mushroom Tricholoma matsutake, with a potent immunogen lipopolysaccharide (LPS), and their molecular mechanisms on the functional activation of macrophages. We found that fraction II (TMF-II) was able to comparably upregulate or highly enhance the phenotypic functions of macrophages such NO production and cytokine (IL-$1{\beta}$, IL-6, IL-12, and TNF-${\alpha}$) expression, to LPS. TMF-II triggered the phosphorylation of $I{\kappa}B{\alpha}$, a critical step for NF-${\kappa}B$ activation and translocation. Of the upstream signaling enzymes tested, Src and Akt were thought to be the responsible upstream signaling components in induction of NO production, although TMF-II strongly upregulated the phosphorylation of all MAPK pathways. Therefore, our data suggest that T. matsutake-derived ${\beta}$-glucan may exert its immunostimulating activities with similar potency to LPS via activation of multiple signaling pathways linked to NF-${\kappa}B$ activation.

Anti-Inflammatory Effect of Asterias amurensis Fatty Acids through NF-κB and MAPK Pathways against LPS-Stimulated RAW264.7 Cells

  • Monmai, Chaiwat;Go, Seok Hyeon;Shin, Il-sik;You, SangGuan;Kim, Dae-ok;Kang, SeokBeom;Park, Woo Jung
    • Journal of Microbiology and Biotechnology
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    • 제28권10호
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    • pp.1635-1644
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    • 2018
  • Asterias amurensis (starfish) is a marine organism that is harmful to the fishing industry, but is also a potential source of functional materials. The present study was conducted to analyze the profiles of fatty acids extracted from A. amurensis tissues and their anti-inflammatory effects on RAW264.7 macrophage cells. In different tissues, the component ratios of saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids differed; particularly, polyunsaturated fatty acids such as dihomo-gamma-linolenic acid (20:3n-6) and eicosapentaenoic acid (20:5n-3) were considerably different. In lipopolysaccharide-stimulated RAW264.7 cells, fatty acids from A. amurensis skin, gonads, and digestive glands exhibited anti-inflammatory activities by reducing nitric oxide production and inducing nitric oxide synthase gene expression. Asterias amurensis fatty acids effectively suppressed the expression of inflammatory cytokines such as tumor necrosis $factor-{\alpha}$, interleukin-$1{\beta}$, and interleukin-6 in lipopolysaccharide-stimulated cells. Cyclooxygenase-2 and prostaglandin $E_2$, which are critical inflammation biomarkers, were also significantly suppressed. Furthermore, A. amurensis fatty acids reduced the phosphorylation of nuclear $factor-{\kappa}B$ p-65, p38, extracellular signal-related kinase 1/2, and c-Jun N-terminal kinase, indicating that these fatty acids ameliorated inflammation through the nuclear $factor-{\kappa}B$ and mitogen-activated protein kinase pathways. These results provide insight into the anti-inflammatory mechanism of A. amurensis fatty acids on immune cells and suggest that the species is a potential source of anti-inflammatory molecules.

Lysophosphatidic acid enhances breast cancer cells-mediated osteoclastogenesis

  • Nam, Ju-Suk;Sharma, Ashish Ranjan;Nguyen, Lich Thi;Jagga, Supriya;Lee, Yeon-Hee;Sharma, Garima;Lee, Sang-Soo
    • The Korean Journal of Physiology and Pharmacology
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    • 제22권5호
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    • pp.503-511
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    • 2018
  • Lysophosphatidic acid (LPA) is known to play a critical role in breast cancer metastasis to bone. In this study, we tried to investigate any role of LPA in the regulation of osteoclastogenic cytokines from breast cancer cells and the possibility of these secretory factors in affecting osteoclastogenesis. Effect of secreted cytokines on osteoclastogenesis was analyzed by treating conditioned media from LPA-stimulated breast cancer cells to differentiating osteoclasts. Result demonstrated that IL-8 and IL-11 expression were upregulated in LPA-treated MDA-MB-231 cells. IL-8 was induced in both MDA-MB-231 and MDA-MB-468, however, IL-11 was induced only in MDA-MB-231, suggesting differential LPARs participation in the expression of these cytokines. Expression of IL-8 but not IL-11 was suppressed by inhibitors of PI3K, NF-kB, ROCK and PKC pathways. In the case of PKC activation, it was observed that $PKC{\delta}$ and $PKC{\mu}$ might regulate LPA-induced expression of IL-11 and IL-8, respectively, by using specific PKC subtype inhibitors. Finally, conditioned Medium from LPA-stimulated breast cancer cells induced osteoclastogenesis. In conclusion, LPA induced the expression of osteolytic cytokines (IL-8 and IL-11) in breast cancer cells by involving different LPA receptors. Enhanced expression of IL-8 by LPA may be via ROCK, PKCu, PI3K, and NFkB signaling pathways, while enhanced expression of IL-11 might involve $PKC{\delta}$ signaling pathway. LPA has the ability to enhance breast cancer cells-mediated osteoclastogenesis by inducing the secretion of cytokines such as IL-8 and IL-11.