• 제목/요약/키워드: metabolic regulation

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Molecular Mechanisms of T Helper Cell Differentiation and Functional Specialization

  • Gap Ryol Lee
    • IMMUNE NETWORK
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    • 제23권1호
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    • pp.4.1-4.15
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    • 2023
  • Th cells, which orchestrate immune responses to various pathogens, differentiate from naive CD4 T cells into several subsets that stimulate and regulate immune responses against various types of pathogens, as well as a variety of immune-related diseases. Decades of research have revealed that the fate decision processes are controlled by cytokines, cytokine receptor signaling, and master transcription factors that drive the differentiation programs. Since the Th1 and Th2 paradigm was proposed, many subsets have been added to the list. In this review, I will summarize these events, including the fate decision processes, subset functions, transcriptional regulation, metabolic regulation, and plasticity and heterogeneity. I will also introduce current topics of interest.

무 자엽의 노쇠에 미치는 Triacontanol의 효과 (Effects of Triacontanol on Senescence of Radish (Raphanus sativus L.) Cotyledons)

  • 진창덕
    • Journal of Plant Biology
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    • 제32권4호
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    • pp.293-304
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    • 1989
  • Effects of triacontanol(TRIA) on several parameters of senescence including the changes of related enzyme activities were investigated in radish(Raphanus sativus L._ cotyledons developing in light. In senescing radish cotyledons, 1.0mg TRIA/1 retarded the degradation of chlorophyll content. Moreover, it depressed the increases of malondialdehyde and H2O2 contents compared to the control. Catalase and superoxide dismutase activities were highly maintained but the increase of peroxidase activity was inhibited remarkably under the TRIA application. These results suggested that TRIA participated in the regulation of senescence during the late part of cotyledon development where it delayed senescence through its action on free radical-associated enzymes and consequent metabolic turnover.

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네트워크 약리학을 통한 황기의 항비만 효능 및 작용기전 예측 연구 (Prediction of functional molecular machanism of Astragalus membranaceus on obesity via network pharmacology analysis)

  • 김미혜
    • 대한본초학회지
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    • 제38권1호
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    • pp.45-53
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    • 2023
  • Objectives : Network pharmacology-based research is one of useful tool to predict the possible efficacy and molecular mechanisms of natural materials with multi compounds-multi targeting effects. In this study, we investigated the functional underlying mechanisms of Astragalus membranaceus Bunge (AM) on its anti-obesity effects using a network pharmacology analysis. Methods : The constituents of AM were collected from public databases and its target genes were gathered from PubChem database. The target genes of AM were compared with the gene set of obesity to find the correlation. Then, the network was constructed by Cytoscape 3.9.1. and functional enrichment analysis was conducted to predict the most relevant pathway of AM. Results : The result showed that AM network contained the 707 nodes and 6867 edges, and 525 intersecting genes were exhibited between AM and obesity gene set, indicating that high correlation with the effects of AM on obesity. Based on GO biological process and KEGG Pathway, 'Response to lipid', 'Cellular response to lipid', 'Lipid metabolic process', 'Regulation of chemokine production', 'Regulation of lipase activity', 'Chemokine signaling pathway', 'Regulation of lipolysis in adipocytes' and 'PPAR signaling pathway' were predicted as functional pathways of AM on obesity. Conclusions : AM showed high relevance with the lipid metabolism related with the chemokine production and lipolysis pathways. This study could be a basis that AM has promising effects on obesity via network pharmacology analysis.

Allithiamine Exerts Therapeutic Effects on Sepsis by Modulating Metabolic Flux during Dendritic Cell Activation

  • Choi, Eun Jung;Jeon, Chang Hyun;Park, Dong Ho;Kwon, Tae-Hwan
    • Molecules and Cells
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    • 제43권11호
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    • pp.964-973
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    • 2020
  • Recent studies have highlighted that early enhancement of the glycolytic pathway is a mode of maintaining the proinflammatory status of immune cells. Thiamine, a wellknown co-activator of pyruvate dehydrogenase complex, a gatekeeping enzyme, shifts energy utilization of glucose from glycolysis to oxidative phosphorylation. Thus, we hypothesized that thiamine may modulate inflammation by alleviating metabolic shifts during immune cell activation. First, using allithiamine, which showed the most potent anti-inflammatory capacity among thiamine derivatives, we confirmed the inhibitory effects of allithiamine on the lipopolysaccharide (LPS)-induced pro-inflammatory cytokine production and maturation process in dendritic cells. We applied the LPS-induced sepsis model to examine whether allithiamine has a protective role in hyper-inflammatory status. We observed that allithiamine attenuated tissue damage and organ dysfunction during endotoxemia, even when the treatment was given after the early cytokine release. We assessed the changes in glucose metabolites during LPS-induced dendritic cell activation and found that allithiamine significantly inhibited glucose-driven citrate accumulation. We then examined the clinical implication of regulating metabolites during sepsis by performing a tail bleeding assay upon allithiamine treatment, which expands its capacity to hamper the coagulation process. Finally, we confirmed that the role of allithiamine in metabolic regulation is critical in exerting anti-inflammatory action by demonstrating its inhibitory effect upon mitochondrial citrate transporter activity. In conclusion, thiamine could be used as an alternative approach for controlling the immune response in patients with sepsis.

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.

Mitochondrial energy metabolic transcriptome profiles during cardiac differentiation from mouse and human pluripotent stem cells

  • Cho, Sung Woo;Kim, Hyoung Kyu;Sung, Ji Hee;Kim, Yeseul;Kim, Jae Ho;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • 제26권5호
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    • pp.357-365
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    • 2022
  • Simultaneous myofibril and mitochondrial development is crucial for the cardiac differentiation of pluripotent stem cells (PSCs). Specifically, mitochondrial energy metabolism (MEM) development in cardiomyocytes is essential for the beating function. Although previous studies have reported that MEM is correlated with cardiac differentiation, the process and timing of MEM regulation for cardiac differentiation remain poorly understood. Here, we performed transcriptome analysis of cells at specific stages of cardiac differentiation from mouse embryonic stem cells (mESCs) and human induced PSCs (hiPSCs). We selected MEM genes strongly upregulated at cardiac lineage commitment and in a time-dependent manner during cardiac maturation and identified the protein-protein interaction networks. Notably, MEM proteins were found to interact closely with cardiac maturation-related proteins rather than with cardiac lineage commitment-related proteins. Furthermore, MEM proteins were found to primarily interact with cardiac muscle contractile proteins rather than with cardiac transcription factors. We identified several candidate MEM regulatory genes involved in cardiac lineage commitment (Cck, Bdnf, Fabp4, Cebpα, and Cdkn2a in mESC-derived cells, and CCK and NOS3 in hiPSC-derived cells) and cardiac maturation (Ppargc1α, Pgam2, Cox6a2, and Fabp3 in mESC-derived cells, and PGAM2 and SLC25A4 in hiPSC-derived cells). Therefore, our findings show the importance of MEM in cardiac maturation.

정상 갑상샘 기능을 보이는 성인 남성에서 갑상샘 호르몬과 대사증후군 위험요인과의 관계 (Association between Thyroid Hormone and Risk Factors of Metabolic Syndrome in Adult Men of Normal Thyroid Function)

  • 신경아
    • 대한임상검사과학회지
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    • 제47권4호
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    • pp.324-331
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    • 2015
  • 갑상샘 호르몬은 교감신경계와의 상호작용으로 세포의 에너지 대사조절 및 항상성 유지에 중요한 역할을 한다. 본 연구는 건강검진을 실시한 성인 남성을 대상으로 갑상샘 호르몬과 대사증후군 위험요인간의 연관성을 밝히고자 하였다. 경기지역 일개 종합병원에서 2011년 1월부터 2013년 12월까지 건강검진센터에서 종합건강검진을 실시한 20세 이상 80세 이하의 남성 12,250명을 대상으로 하였다. 대사증후군은 American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI, 2005)에서 제시한 진단 기준에 따랐으며, 3개 이상의 위험요인을 가진 경우 대사증후군으로 진단하였다. 정상군보다 대사증후군 진단군에서 FT4가 낮았으며(p<0.001), TSH는 대사증후군 유무에 따른 차이는 없었다. 또한 FT4는 대사증후군 위험요인 중 허리둘레, 중성지방에 영향을 미치는 것으로 나타났으며(각각 p<0.001), FT4의 가장 낮은 사분위수가 가장 높은 사분위수보다 HbA1c, 인슐린, HOMA-IR, hs-CRP 농도가 높았다(각각 p<0.001). FT4는 허리둘레, 중성지방에 영향을 미치는 것으로 나타났으나, TSH는 대사증후군 위험요인에 영향을 미치지 않는 것으로 나타났다. 또한 FT4의 가장 높은 분위수의 대사증후군 발생위험이 가장 낮은 분위수보다 낮게 나타났다.

세균성 질병 예방을 위한 식물 경구 백신 연구 동향 (Recent Studies on the Edible Plant Vaccine for Prophylactic Medicine against Microorganism-Mediated Diseases)

  • 한범수;정영재;노경희;박종석;조강진;김용환;김종범
    • Journal of Plant Biotechnology
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    • 제32권4호
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    • pp.233-241
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    • 2005
  • Plants have considerable advantages for the production of antigenic proteins because they provide an inexpensive source of protein and an easy administration of vaccine. Since a publication describing edible plant vaccine of HBsAg in 1992, a number of laboratories around the world have studied the use of plants as the bioreactor to produce antigenic proteins of human or animal pathogens. Over the last ten years, these works have been mainly focused on three major strategies for the production of antigenic proteins in plants: stable genetic transformation of either the nuclear or plastid genome, or transient expression in plants using viral vectors. As many antigenic proteins have been expressed in tobacco, also several laboratories have succeeded to express genes encoding antigenic proteins in other crop plants: potato, tomato, maize, carrot, soybean and spinach. At present many works for the production of edible plant vaccine against bacteria-mediated diseases have mostly performed the studies of enterotoxins and adhesion proteins. Also the development of new-type antigens (pili, flagella, surface protein, other enterotoxin and exotoxin etc.) is required for various targets and more efficacy to immunize against microorganism pathogens. Many works mostly studied in experimental animals had good results, and phase I clinical trial of LTB clearly indicated its immunogenic ability. On the other hand, edible plant vaccines have still problems remained to be solved. In addition to the accumulation of sufficient antigen in plants, human health, environment and agriculture regulation should be proven. Also oral tolerance, the physiological response to food antigens and commensal flora is the induction of a state of specific immunological unresponsiveness, needs to be addressed before plant-derived vaccine becomes a therapeutic option.

Effects of aged garlic extract and endurance exercise on skeletal muscle FNDC-5 and circulating irisin in high-fat-diet rat models

  • Seo, Dae Yun;Kwak, Hyo Bum;Lee, Sung Ryul;Cho, Yeun Suk;Song, In-Sung;Kim, Nari;Bang, Hyun Seok;Rhee, Byoung Doo;Ko, Kyung Soo;Park, Byung Joo;Han, Jin
    • Nutrition Research and Practice
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    • 제8권2호
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    • pp.177-182
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    • 2014
  • BACKGROUND/OBJECTIVES: Irisin, a newly identified hormone, is associated with energy homeostasis. We investigated whether aged garlic extract (AGE) and exercise training intervention could improve body weight, insulin sensitivity, skeletal muscle fibronectin domain containing protein 5 (FNDC-5) levels, and plasma irisin in high-fat diet (HFD). MATERIALS/METHODS: Male Sprague Dawley rats were fed a ND (normal diet, n=5) or HFD (n=28) for 6 weeks. After 6 weeks, all rats were divided into 5 groups for the next 4 weeks: ND, (normal diet, n=5), HFD (high-fat diet, n=7), HFDA (high-fat diet + aged garlic extract, n=7), HFDE (high-fat diet + exercise, n=7), and HFDEA (high-fat diet + exercise + aged garlic extract, n=7). Exercise groups performed treadmill exercises for 15-60 min, 5 days/week, and AGE groups received AGE (2.86 g/kg, orally injected) for 4 weeks. RESULTS: Significant decreases in body weight were observed in the ND, HFDE, and HFDEA groups, as compared with the HFD group. Neither intervention affected the masses of the gastrocnemius muscle or liver. There were no significant differences in glucose levels across the groups. The homeostatic model assessments of insulin resistance were significantly higher in the HFD group, as compared with the ND, HFDA, HFDE, and HFDEA groups. However, skeletal muscle FNDC-5 levels and plasma irisin concentrations were unaffected by AGE or exercise in obese rats. AGE supplementation and exercise training did not affect skeletal muscle FNDC-5 or plasma irisin, which are associated with insulin sensitivity in obese rats. CONCLUSION: Our results suggest that the protection against HFD-induced increases in body fat/weight and insulin resistance that are provided by AGE supplementation and exercise training may not be mediated by the regulation of FNDC-5 or irisin.

세포내 소기관과 물질대사의 관점에서 오이 떡잎의 발달 (Development of Cucumber Cotyledon in View of Metabolic Pathways and Organelle)

  • 김대재
    • 생명과학회지
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    • 제31권8호
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    • pp.778-785
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    • 2021
  • 오이 씨앗의 발아는 세포의 지방체내 저장지방의 분해 결과인 acyl-CoA의 글라이옥시좀으로 이동 후 베타 산화의 결과물인 acetyl-CoA의 글라이옥실산 회로로의 유입과 지방의 유동으로 촉발된다. Acetyl-CoA는 글라이옥실산 회로의 가동을 위한 탄소원을 제공하며 시트르산과 말산을 생성하며 글라이옥실산 회로의 작동을 유도한다. 지방 저장 종자의 발아에 있어서 글라이옥실산 회로는 필수적 요소이며, 그 결과물인 말산 및 숙신산의 미토콘드리아로의 이동은 TCA 회로의 가동과 옥살초산의 생성 및 세포질로의 유동으로 PEPCK에 의한 당신생을 가능하게 한다. 즉, 저장 지방을 원료로 여러 대사물질의 생산 및 이동과 다중의 대사경로를 통하여 발아 시 사용 가능한 에너지원인 포도당의 형태로 전환이 이루어진다. 이에 동반하여 많은 유전자의 발현 조절이 이루어지고, 세포내 소기관 특히 미소체로 대표되는 글라이옥시좀은 말산 합성효소(malate synthase)와 이소 시트르산 분해효소(isocitrate lyase)로 특화된다. 또 다른 acetyl-CoA의 유동은 carnitine을 매개로 하는 BOU (A BOUT DE SOUFFLE)의 작동이다. 이것은 카니틴의 대사와 관련하여 고등식물의 발달과 대사과정에서의 중요성이 확인된 것으로 사료된다.