Role of nuclear factor κB in liver health and disease

2010 ◽  
Vol 118 (12) ◽  
pp. 691-705 ◽  
Author(s):  
Stuart M. Robinson ◽  
Derek A. Mann
Keyword(s):  
Hepatocellular Carcinoma ◽  
Current Knowledge ◽  
Transcriptional Regulator ◽  
Cell Types ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Liver Health ◽  
Health And Disease ◽  
Experimental Approaches

NF-κB (nuclear factor κB) is a heterodimeric transcription factor that is constitutively expressed in all cell types and has a central role as a transcriptional regulator in response to cellular stress. In the present review, we discuss the role of NF-κB signalling in the maintenance of liver homoeostasis as well as in the pathogenesis of a wide variety of conditions affecting the liver, including viral hepatitis, steatohepatitis, cirrhosis and hepatocellular carcinoma. Much of the current knowledge of NF-κB signalling in the liver relates to the canonical pathway, the IKK [IκB (inhibitor of κB) kinase] complex and the RelA subunit. We explore the weaknesses of the experimental approaches to date and suggest that further work is needed to investigate in detail the discreet functions of each of the Rel subunits in liver physiology and disease.

PKCθ-regulated signalling in health and disease

2014 ◽  
Vol 42 (6) ◽  
pp. 1484-1489 ◽  
Author(s):  
Pulak R. Nath ◽  
Noah Isakov
Keyword(s):  
Signal Transduction ◽  
T Cells ◽  
T Cell ◽  
Immunological Synapse ◽  
Cell Types ◽  
Cell Receptor ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Health And Disease

Protein kinase Cθ (PKCθ) is a key enzyme in T-lymphocytes where it plays an important role in signal transduction downstream of the activated T-cell receptor (TCR) and the CD28 co-stimulatory receptor. Antigenic stimulation of T-cells triggers PKCθ translocation to the centre of the immunological synapse (IS) at the contact site between antigen-specific T-cells and antigen-presenting cells (APCs). The IS-residing PKCθ phosphorylates and activates effector molecules that transduce signals into distinct subcellular compartments and activate the transcription factors, nuclear factor κB (NF-κB), nuclear factor of activated T-cells (NFAT) and activating protein 1 (AP-1), which are essential for the induction of T-cell-mediated responses. Besides its major biological role in T-cells, PKCθ is expressed in several additional cell types and is involved in a variety of distinct physiological and pathological phenomena. For example, PKCθ is expressed at high levels in platelets where it regulates signal transduction from distinct surface receptors, and is required for optimal platelet activation and aggregation, as well as haemostasis. In addition, PKCθ is involved in physiological processes regulating insulin resistance and susceptibility to obesity, and is expressed at high levels in gastrointestinal stromal tumours (GISTs), although the functional importance of PKCθ in these processes and cell types is not fully clear. The present article briefly reviews selected topics relevant to the biological roles of PKCθ in health and disease.

Regulation of cyclin D1 gene expression

2010 ◽  
Vol 38 (1) ◽  
pp. 217-222 ◽  
Author(s):  
Ini-Isabée Witzel ◽  
Li Fang Koh ◽  
Neil D. Perkins
Keyword(s):  
Gene Expression ◽  
Cyclin D1 ◽  
Rna Processing ◽  
Dominant Role ◽  
Rna Stability ◽  
Transcriptional Regulator ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Post Transcriptional Regulation

Cyclin D1 is a key regulator of cell proliferation and its expression is subject to both transcriptional and post-transcriptional regulation. In different cellular contexts, different pathways assume a dominant role in regulating its expression, whereas their disregulation can contribute to overexpression of cyclin D1 in tumorigenesis. Here, we discuss the ability of the NF-κB (nuclear factor κB)/IKK [IκB (inhibitor of NF-κB) kinase] pathways to regulate cyclin D1 gene transcription and also consider the newly discovered role of the SNARP (SNIP1/SkIP-associated RNA processing) complex as a co-transcriptional regulator of cyclin D1 RNA stability.

The role of SLAM family receptors in immune cell signalingThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB — Membrane Proteins in Health and Disease.

2006 ◽  
Vol 84 (6) ◽  
pp. 832-843 ◽  
Author(s):  
Elena A. Ostrakhovitch ◽  
Shawn S.-C. Li
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Current Knowledge ◽  
Critical Role ◽  
Cell Types ◽  
Health And Disease ◽  
Slam Family ◽  
Different Cell Types ◽  
Selection Of

The signaling lymphocyte-activating molecule (SLAM) family immunoreceptors are expressed in a wide array of immune cells, including both T and B lymphocytes. By virtue of their ability to transduce tyrosine phosphorylation signals through the so-called ITSM (immunoreceptor tyrosine-based switch motif) sequences, they play an important part in regulating both innate and adaptive immune responses. The critical role of the SLAM immunoreceptors in mediating normal immune reactions was highlighted in recent findings that SAP, a SLAM-associated protein, modulates the activities of various immune cells through interactions with different members of the SLAM family expressed in these cells. Importantly, mutations or deletions of the sap gene in humans result in the X-linked lymphoproliferative syndrome. In this review, we summarize current knowledge and survey the latest developments in signal transduction events triggered by the activation of SLAM family receptors in different cell types.

scholarly journals Lysosome function in glomerular health and disease

2021 ◽  
Author(s):  
Catherine Meyer-Schwesinger
Keyword(s):  
Current Knowledge ◽  
Lysosomal Storage Diseases ◽  
Cell Types ◽  
Lysosomal Storage ◽  
Membrane Repair ◽  
Glomerular Cell ◽  
Wide Range ◽  
Center Position ◽  
Health And Disease

AbstractThe lysosome represents an important regulatory platform within numerous vesicle trafficking pathways including the endocytic, phagocytic, and autophagic pathways. Its ability to fuse with endosomes, phagosomes, and autophagosomes enables the lysosome to break down a wide range of both endogenous and exogenous cargo, including macromolecules, certain pathogens, and old or damaged organelles. Due to its center position in an intricate network of trafficking events, the lysosome has emerged as a central signaling node for sensing and orchestrating the cells metabolism and immune response, for inter-organelle and inter-cellular signaling and in membrane repair. This review highlights the current knowledge of general lysosome function and discusses these findings in their implication for renal glomerular cell types in health and disease including the involvement of glomerular cells in lysosomal storage diseases and the role of lysosomes in nongenetic glomerular injuries.

scholarly journals The Role of Exosomes in Bone Remodeling: Implications for Bone Physiology and Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Christos Masaoutis ◽  
Stamatios Theocharis
Keyword(s):  
Bone Remodeling ◽  
Current Knowledge ◽  
Active Role ◽  
Cell Types ◽  
Matrix Mineralization ◽  
Physiological Phenomenon ◽  
Health And Disease ◽  
Multiple Cell ◽  
Bone Physiology

Bone remodeling represents a physiological phenomenon of continuous bone tissue renewal that requires fine orchestration of multiple cell types, which is critical for the understanding of bone disease but not yet clarified in precise detail. Exosomes, which are cell-secreted nanovesicles drawing increasing attention for their broad biosignaling functions, can shed new light on how multiple heterogeneous cells communicate for the purpose of bone remodeling. In the healthy bone, exosomes transmit signals favoring both bone synthesis and resorption, regulating the differentiation, recruitment, and activity of most cell types involved in bone remodeling and even assuming an active role in extracellular matrix mineralization. Additionally, in the ailing bone, they actively participate in pathogenic processes constituting also potential therapeutic agents and drug vectors. The present review summarizes the current knowledge on bone exosomes and bone remodeling in health and disease.

scholarly journals The Mechanisms of CHD8 in Neurodevelopment and Autism Spectrum Disorders

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1133
Author(s):  
Orly Weissberg ◽  
Evan Elliott
Keyword(s):  
Neuronal Development ◽  
Mutant Mouse ◽  
Current Knowledge ◽  
Transcriptional Regulator ◽  
Cell Types ◽  
Dna Binding Protein ◽  
Autism Spectrum ◽  
Cellular Processes ◽  
Spectrum Disorders

Chromodomain-helicase-DNA-binding protein 8 (CHD8) has been identified as one of the genes with the strongest association with autism. The CHD8 protein is a transcriptional regulator that is expressed in nearly all cell types and has been implicated in multiple cellular processes, including cell cycle, cell adhesion, neuronal development, myelination, and synaptogenesis. Considering the central role of CHD8 in the genetics of autism, a deeper understanding of the physiological functions of CHD8 is important to understand the development of the autism phenotype and potential therapeutic targets. Different CHD8 mutant mouse models were developed to determine autism-like phenotypes and to fully understand their mechanisms. Here, we review the current knowledge on CHD8, with an emphasis on mechanistic lessons gained from animal models that have been studied.

Genistein potentiates the effect of arsenic trioxide against human hepatocellular carcinoma: Role of Akt and nuclear factor-κB

2011 ◽  
Vol 301 (1) ◽  
pp. 75-84 ◽  
Author(s):  
Yong Ma ◽  
Jizhou Wang ◽  
Lianxin Liu ◽  
Huaqiang Zhu ◽  
Xiaoning Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Arsenic Trioxide ◽  
Nuclear Factor Κb ◽  
Human Hepatocellular Carcinoma ◽  
Nuclear Factor

scholarly journals NF-κB, JNK, and TLR Signaling Pathways in Hepatocarcinogenesis

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Shin Maeda
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathways ◽  
Inflammatory Cell ◽  
Prognostic Markers ◽  
Tumor Promotion ◽  
Neoplastic Cell ◽  
Nuclear Factor ◽  
Tlr Signaling ◽  
The Third

Hepatocellular carcinoma (HCC) is the third largest cause of cancer deaths worldwide. The role of molecular changes in HCC have been used to identify prognostic markers and chemopreventive or therapeutic targets. It seems that toll-like receptors (TLRs) as well as the nuclear factor (NF)-κB, and JNK pathways are critical regulators for the production of the cytokines associated with tumor promotion. The cross-talk between an inflammatory cell and a neoplastic cell, which is instigated by the activation of NF-κB and JNKs, is critical for tumor organization. JNKs also regulate cell proliferation and act as oncogenes, making them the main tumor-promoting protein kinases. TLRs play roles in cytokine and hepatomitogen expression mainly in myeloid cells and may promote liver tumorigenesis. A better understanding of these signaling pathways in the liver will help us understand the mechanism of hepatocarcinogenesis and provide a new therapeutic target for HCC.

scholarly journals Hypoxia, Acidification and Inflammation: Partners in Crime in Parkinson’s Disease Pathogenesis?

Immuno ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 78-90
Author(s):  
Johannes Burtscher ◽  
Grégoire P. Millet
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Current Knowledge ◽  
Cell Types ◽  
Brain Cell ◽  
Special Focus ◽  
Molecular Alterations ◽  
Research Fields

Like in other neurodegenerative diseases, protein aggregation, mitochondrial dysfunction, oxidative stress and neuroinflammation are hallmarks of Parkinson’s disease (PD). Differentiating characteristics of PD include the central role of α-synuclein in the aggregation pathology, a distinct vulnerability of the striato-nigral system with the related motor symptoms, as well as specific mitochondrial deficits. Which molecular alterations cause neurodegeneration and drive PD pathogenesis is poorly understood. Here, we summarize evidence of the involvement of three interdependent factors in PD and suggest that their interplay is likely a trigger and/or aggravator of PD-related neurodegeneration: hypoxia, acidification and inflammation. We aim to integrate the existing knowledge on the well-established role of inflammation and immunity, the emerging interest in the contribution of hypoxic insults and the rather neglected effects of brain acidification in PD pathogenesis. Their tight association as an important aspect of the disease merits detailed investigation. Consequences of related injuries are discussed in the context of aging and the interaction of different brain cell types, in particular with regard to potential consequences on the vulnerability of dopaminergic neurons in the substantia nigra. A special focus is put on the identification of current knowledge gaps and we emphasize the importance of related insights from other research fields, such as cancer research and immunometabolism, for neurodegeneration research. The highlighted interplay of hypoxia, acidification and inflammation is likely also of relevance for other neurodegenerative diseases, despite disease-specific biochemical and metabolic alterations.

ROLE OF NUCLEAR FACTOR κB IN MELANOMA PROGRESSION.

2007 ◽  
Vol 55 (1) ◽  
pp. S158
Author(s):  
A. M. DeLuca ◽  
B. Ryu ◽  
R. Alani
Keyword(s):  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Melanoma Progression
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