• Title/Summary/Keyword: systemic regulation

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The FMRFamide Neuropeptide FLP-20 Acts as a Systemic Signal for Starvation Responses in Caenorhabditis elegans

  • Kang, Chanhee;Avery, Leon
    • Molecules and Cells
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    • v.44 no.7
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    • pp.529-537
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    • 2021
  • Most animals face frequent periods of starvation throughout their entire life and thus need to appropriately adjust their behavior and metabolism during starvation for their survival. Such adaptive responses are regulated by a complex set of systemic signals, including hormones and neuropeptides. While much progress has been made in identifying pathways that regulate nutrient-excessive states, it is still incompletely understood how animals systemically signal their nutrient-deficient states. Here, we showed that the FMRFamide neuropeptide FLP-20 modulates a systemic starvation response in Caenorhabditis elegans. We found that mutation of flp-20 rescued the starvation hypersensitivity of the G protein β-subunit gpb-2 mutants by suppressing excessive autophagy. FLP-20 acted in AIB neurons, where the metabotropic glutamate receptor MGL-2 also functions to modulate a systemic starvation response. Furthermore, FLP-20 modulated starvation-induced fat degradation in a manner dependent on the receptor-type guanylate cyclase GCY-28. Collectively, our results reveal a circuit that senses and signals nutrient-deficient states to modulate a systemic starvation response in multicellular organisms.

MicroRNA Regulation in Systemic Lupus Erythematosus Pathogenesis

  • Yan, Sheng;Yim, Lok Yan;Lu, Liwei;Lau, Chak Sing;Chan, Vera Sau-Fong
    • IMMUNE NETWORK
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    • v.14 no.3
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    • pp.138-148
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    • 2014
  • MicroRNAs (miRNAs) are endogenous small RNA molecules best known for their function in post-transcriptional gene regulation. Immunologically, miRNA regulates the differentiation and function of immune cells and its malfunction contributes to the development of various autoimmune diseases including systemic lupus erythematosus (SLE). Over the last decade, accumulating researches provide evidence for the connection between dysregulated miRNA network and autoimmunity. Interruption of miRNA biogenesis machinery contributes to the abnormal T and B cell development and particularly a reduced suppressive function of regulatory T cells, leading to systemic autoimmune diseases. Additionally, multiple factors under autoimmune conditions interfere with miRNA generation via key miRNA processing enzymes, thus further skewing the miRNA expression profile. Indeed, several independent miRNA profiling studies reported significant differences between SLE patients and healthy controls. Despite the lack of a consistent expression pattern on individual dysregulated miRNAs in SLE among these studies, the aberrant expression of distinct groups of miRNAs causes overlapping functional outcomes including perturbed type I interferon signalling cascade, DNA hypomethylation and hyperactivation of T and B cells. The impact of specific miRNA-mediated regulation on function of major immune cells in lupus is also discussed. Although research on the clinical application of miRNAs is still immature, through an integrated approach with advances in next generation sequencing, novel tools in bioinformatics database analysis and new in vitro and in vivo models for functional evaluation, the diagnostic and therapeutic potentials of miRNAs may bring to fruition in the future.

Assessing the Contributions of Non-bank Financial Institutions (NBFI) and ELS Issuance to Systemic Risk in Korea

  • JONG SOO HONG
    • KDI Journal of Economic Policy
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    • v.46 no.1
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    • pp.21-51
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    • 2024
  • Since the Global Financial Crisis of 2008-2009, the importance of nonbank financial institutions in macroprudential management has increased significantly. Consequently, major countries and international financial institutions have been actively discussing and implementing macroprudential supervision and regulation for non-bank financial institutions (NBFI). In this context, this paper analyzes the systemic risk of both banks and non-bank sectors (securities firms and insurance companies) in South Korea over different time periods. Using the widely recognized ΔCoVaR methodology for measuring systemic risk, the analysis reveals that systemic risk increased substantially across all three sectors (banks, securities firms, and insurance companies) during the Global Financial Crisis, the European Sovereign Debt Crisis, and the COVID-19 pandemic. Although the banking sector exhibited relatively high systemic risk compared to the securities and insurance sectors, the relative differences in systemic risk varied across the different crisis periods. Notably, during the margin call crisis in March of 2020, the gap in systemic risk between the banking and securities sectors decreased significantly compared to that during both the Global Financial Crisis and the European Sovereign Debt Crisis, indicating that securities firms had a more substantial impact on risk in the overall financial system during this period. Furthermore, I analyze the impact of the issuance of equity-linked securities (ELS) by financial institutions on systemic risk, as measured by ΔCoVaR, finding that an increase in the outstanding balance of ELS issuance by financial institutions had an impact on increasing ΔCoVaR during the three crisis periods. These findings underscore the growing importance of non-bank financial institutions in relation to South Korea's macroprudential management and supervision. To address this evolving landscape, enhanced monitoring and regulatory measures focusing on non-bank systemic risk are essential components of maintaining financial stability in the country.

Cellular and Molecular Links between Autoimmunity and Lipid Metabolism

  • Ryu, Heeju;Kim, Jiyeon;Kim, Daehong;Lee, Jeong-Eun;Chung, Yeonseok
    • Molecules and Cells
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    • v.42 no.11
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    • pp.747-754
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    • 2019
  • The incidence of atherosclerosis is higher among patients with several autoimmune diseases such as psoriasis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). It is well documented that innate immune cells including macrophages and dendritic cells sense lipid species such as saturated fatty acids and oxidized low-density lipoprotein and produce pro-inflammatory cytokines and chemokines. However, whether a hyperlipidemic environment also impacts autoimmune T cell responses has been unclear. Among $CD4^+$ T cells, Th17 and follicular helper T (Tfh) cells are known to play pathogenic roles in the development of hyperlipidemia-associated autoimmune diseases. This review gives an overview of the cellular and molecular mechanisms by which dysregulated lipid metabolism impacts the pathogenesis of autoimmune diseases, with specific emphasis on Th17 and Tfh cells.

Post-translational Modifications and Their Biological Functions: Proteomic Analysis and Systematic Approaches

  • Seo, Ja-Won;Lee, Kong-Joo
    • BMB Reports
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    • v.37 no.1
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    • pp.35-44
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    • 2004
  • Recently produced information on post-translational modifications makes it possible to interpret their biological regulation with new insights. Various protein modifications finely tune the cellular functions of each protein. Understanding the relationship between post-translational modifications and functional changes ("post-translatomics") is another enormous project, not unlike the human genome project. Proteomics, combined with separation technology and mass spectrometry, makes it possible to dissect and characterize the individual parts of post-translational modifications and provide a systemic analysis. Systemic analysis of post-translational modifications in various signaling pathways has been applied to illustrate the kinetics of modifications. Availability will advance new technologies that improve sensitivity and peptide coverage. The progress of "post-translatomics", novel analytical technologies that are rapidly emerging, offer a great potential for determining the details of the modification sites.

Understanding insomnia as systemic disease

  • Yun, Seokho;Jo, Sohye
    • Journal of Yeungnam Medical Science
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    • v.38 no.4
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    • pp.267-274
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    • 2021
  • Sleep plays a critical role in homeostasis of the body and mind. Insomnia is a disease that causes disturbances in the initiation and maintenance of sleep. Insomnia is known to affect not only the sleep process itself but also an individual's cognitive function and emotional regulation during the daytime. It increases the risk of various neuropsychiatric diseases such as depression, anxiety disorder, and dementia. Although it might appear that insomnia only affects the nervous system, it is also a systemic disease that affects several aspects of the body, such as the cardiovascular, endocrine, and immune systems; therefore, it increases the risk of various diseases such as hypertension, diabetes mellitus, and infection. Insomnia has a wide range of effects on our bodies because sleep is a complex and active process. However, a high proportion of patients with insomnia do not seek treatment, which results in high direct and indirect costs. This is attributed to the disregard of many of the negative effects of insomnia. Therefore, we expect that understanding insomnia as a systemic disease will provide an opportunity to understand the condition better and help prevent secondary impairment due to insomnia.

Regulation of Salicylic Acid and N-Hydroxy-Pipecolic Acid in Systemic Acquired Resistance

  • Gah-Hyun, Lim
    • The Plant Pathology Journal
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    • v.39 no.1
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    • pp.21-27
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    • 2023
  • In plants, salicylic acid (SA) is a central immune signal that is involved in both local and systemic acquired resistance (SAR). In addition to SA, several other chemical signals are also involved in SAR and these include N-hydroxy-pipecolic acid (NHP), a newly discovered plant metabolite that plays a crucial role in SAR. Recent discoveries have led to a better understanding of the biosynthesis of SA and NHP and their signaling during plant defense responses. Here, I review the recent progress in role of SA and NHP in SAR. In addition, I discuss how these signals cooperate with other SAR-inducing chemicals to regulate SAR.

Peripheral Serotonin: a New Player in Systemic Energy Homeostasis

  • Namkung, Jun;Kim, Hail;Park, Sangkyu
    • Molecules and Cells
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    • v.38 no.12
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    • pp.1023-1028
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    • 2015
  • Whole body energy balance is achieved through the coordinated regulation of energy intake and energy expenditure in various tissues including liver, muscle and adipose tissues. A positive energy imbalance by excessive energy intake or insufficient energy expenditure results in obesity and related metabolic diseases. Although there have been many obesity treatment trials aimed at the reduction of energy intake, these strategies have achieved only limited success because of their associated adverse effects. An ancient neurotransmitter, serotonin is among those traditional pharmacological targets for anti-obesity treatment because it exhibits strong anorectic effect in the brain. However, recent studies suggest the new functions of peripheral serotonin in energy homeostasis ranging from the endocrine regulation by gut-derived serotonin to the autocrine/paracrine regulation by adipocyte-derived serotonin. Here, we discuss the role of serotonin in the regulation of energy homeostasis and introduce peripheral serotonin as a possible target for anti-obesity treatment.