Current Knowledge of the Nature and Identity of Progestin and Estrogen Membrane Receptors in Fish Gonads

2003 ◽  
pp. 131-137 ◽  
Author(s):  
Peter Thomas ◽  
Zhu Yong ◽  
Pang Yefei
Keyword(s):  
Current Knowledge ◽  
Membrane Receptors ◽  
Fish Gonads

scholarly journals Effects and Mechanisms of Phthalates’ Action on Reproductive Processes and Reproductive Health: A Literature Review

2020 ◽  
Vol 17 (18) ◽  
pp. 6811
Author(s):  
Henrieta Hlisníková ◽  
Ida Petrovičová ◽  
Branislav Kolena ◽  
Miroslava Šidlovská ◽  
Alexander Sirotkin
Keyword(s):  
Reproductive Health ◽  
Human Health ◽  
Intracellular Signaling ◽  
Current Knowledge ◽  
Membrane Receptors ◽  
Reproductive Disorders ◽  
Testicular Dysgenesis Syndrome ◽  
Fertility Disorders ◽  
Reproductive Processes ◽  
Cancer And Fertility

The production of plastic products, which requires phthalate plasticizers, has resulted in the problems for human health, especially that of reproductive health. Phthalate exposure can induce reproductive disorders at various regulatory levels. The aim of this review was to compile the evidence concerning the association between phthalates and reproductive diseases, phthalates-induced reproductive disorders, and their possible endocrine and intracellular mechanisms. Phthalates may induce alterations in puberty, the development of testicular dysgenesis syndrome, cancer, and fertility disorders in both males and females. At the hormonal level, phthalates can modify the release of hypothalamic, pituitary, and peripheral hormones. At the intracellular level, phthalates can interfere with nuclear receptors, membrane receptors, intracellular signaling pathways, and modulate gene expression associated with reproduction. To understand and to treat the adverse effects of phthalates on human health, it is essential to expand the current knowledge concerning their mechanism of action in the organism.

scholarly journals Enzymology of extracellular NAD metabolism

2021 ◽  
Author(s):  
Massimiliano Gasparrini ◽  
Leonardo Sorci ◽  
Nadia Raffaelli
Keyword(s):  
Current Knowledge ◽  
Biochemical Properties ◽  
Extracellular Proteins ◽  
Membrane Receptors ◽  
Intracellular Regeneration ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Nad Metabolism ◽  
Nucleotide Pyrophosphatase ◽  
Nicotinic Acid Phosphoribosyltransferase ◽  
Extracellular Environment

AbstractExtracellular NAD represents a key signaling molecule in different physiological and pathological conditions. It exerts such function both directly, through the activation of specific purinergic receptors, or indirectly, serving as substrate of ectoenzymes, such as CD73, nucleotide pyrophosphatase/phosphodiesterase 1, CD38 and its paralog CD157, and ecto ADP ribosyltransferases. By hydrolyzing NAD, these enzymes dictate extracellular NAD availability, thus regulating its direct signaling role. In addition, they can generate from NAD smaller signaling molecules, like the immunomodulator adenosine, or they can use NAD to ADP-ribosylate various extracellular proteins and membrane receptors, with significant impact on the control of immunity, inflammatory response, tumorigenesis, and other diseases. Besides, they release from NAD several pyridine metabolites that can be taken up by the cell for the intracellular regeneration of NAD itself. The extracellular environment also hosts nicotinamide phosphoribosyltransferase and nicotinic acid phosphoribosyltransferase, which inside the cell catalyze key reactions in NAD salvaging pathways. The extracellular forms of these enzymes behave as cytokines, with pro-inflammatory functions. This review summarizes the current knowledge on the extracellular NAD metabolome and describes the major biochemical properties of the enzymes involved in extracellular NAD metabolism, focusing on the contribution of their catalytic activities to the biological function. By uncovering the controversies and gaps in their characterization, further research directions are suggested, also to better exploit the great potential of these enzymes as therapeutic targets in various human diseases.

scholarly journals The many facets of bile acids in the physiology and pathophysiology of the human liver

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Christoph G.W. Gertzen ◽  
Holger Gohlke ◽  
Dieter Häussinger ◽  
Diran Herebian ◽  
Verena Keitel ◽  
...  
Keyword(s):  
Bile Acids ◽  
Human Liver ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Membrane Receptors ◽  
Vital Functions ◽  
Hereditary Disorders ◽  
The Many ◽  
Analytical Approaches ◽  
G Protein Coupled

Abstract Bile acids perform vital functions in the human liver and are the essential component of bile. It is therefore not surprising that the biology of bile acids is extremely complex, regulated on different levels, and involves soluble and membrane receptors as well as transporters. Hereditary disorders of these proteins manifest in different pathophysiological processes that result in liver diseases of varying severity. In this review, we summarize our current knowledge of the physiology and pathophysiology of bile acids with an emphasis on recently established analytical approaches as well as the molecular mechanisms that underlie signaling and transport of bile acids. In this review, we will focus on ABC transporters of the canalicular membrane and their associated diseases. As the G protein-coupled receptor, TGR5, receives increasing attention, we have included aspects of this receptor and its interaction with bile acids.

scholarly journals Regulation of G Protein-Coupled Receptors by Ubiquitination

2017 ◽  
Author(s):  
Kamila Skieterska ◽  
Pieter Rondou ◽  
Kathleen Van Craenenbroeck
Keyword(s):  
G Protein ◽  
Posttranslational Modifications ◽  
Drug Targets ◽  
Current Knowledge ◽  
G Protein Coupled Receptors ◽  
Membrane Receptors ◽  
Deubiquitinating Enzymes ◽  
Range Of Functions ◽  
Beta Arrestins ◽  
G Protein Coupled

G protein-coupled receptors (GPCRs) comprise the largest family of membrane receptors that control many cellular processes and consequently often serve as drug targets. These receptors undergo a strict regulation by mechanisms such as internalization and desensitization, which are strongly influenced by posttranslational modifications. Ubiquitination is a posttranslational modification with a broad range of functions that is currently gaining increased appreciation as a regulator of GPCR activity. The role of ubiquitination in directing GPCRs for lysosomal degradation has already been well-established. Furthermore, this modification can also play a role in targeting membrane and endoplasmic reticulum-associated receptors to the proteasome. Most recently, ubiquitination was also shown to be involved in GPCR signaling. In this review, we present current knowledge on the molecular basis of GPCR regulation by ubiquitination, and highlight the importance of E3 ubiquitin ligases, deubiquitinating enzymes and β-arrestins. Finally, we discuss classical and newly-discovered functions of ubiquitination in controlling GPCR activity.

scholarly journals JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships

2016 ◽  
Vol 80 (3) ◽  
pp. 793-835 ◽  
Author(s):  
András Zeke ◽  
Mariya Misheva ◽  
Attila Reményi ◽  
Marie A. Bogoyevitch
Keyword(s):  
Current Knowledge ◽  
Eukaryotic Cell ◽  
Membrane Receptors ◽  
Mitogen Activated Protein Kinase ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Cytoplasmic Proteins ◽  
Wide Range ◽  
Complex Protein ◽  
Mitogen Activated Protein

SUMMARYThe c-Jun N-terminal kinases (JNKs), as members of the mitogen-activated protein kinase (MAPK) family, mediate eukaryotic cell responses to a wide range of abiotic and biotic stress insults. JNKs also regulate important physiological processes, including neuronal functions, immunological actions, and embryonic development, via their impact on gene expression, cytoskeletal protein dynamics, and cell death/survival pathways. Although the JNK pathway has been under study for >20 years, its complexity is still perplexing, with multiple protein partners of JNKs underlying the diversity of actions. Here we review the current knowledge of JNK structure and isoforms as well as the partnerships of JNKs with a range of intracellular proteins. Many of these proteins are direct substrates of the JNKs. We analyzed almost 100 of these target proteins in detail within a framework of their classification based on their regulation by JNKs. Examples of these JNK substrates include a diverse assortment of nuclear transcription factors (Jun, ATF2, Myc, Elk1), cytoplasmic proteins involved in cytoskeleton regulation (DCX, Tau, WDR62) or vesicular transport (JIP1, JIP3), cell membrane receptors (BMPR2), and mitochondrial proteins (Mcl1, Bim). In addition, because upstream signaling components impact JNK activity, we critically assessed the involvement of signaling scaffolds and the roles of feedback mechanisms in the JNK pathway. Despite a clarification of many regulatory events in JNK-dependent signaling during the past decade, many other structural and mechanistic insights are just beginning to be revealed. These advances open new opportunities to understand the role of JNK signaling in diverse physiological and pathophysiological states.

scholarly journals A Signaling View into the Inflammatory Tumor Microenvironment

Immuno ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 91-118
Author(s):  
Joana F. S. Pereira ◽  
Peter Jordan ◽  
Paulo Matos
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Chromosomal Abnormalities ◽  
Current Knowledge ◽  
Genetic Alterations ◽  
Malignant Progression ◽  
Membrane Receptors ◽  
Surrounding Tissue ◽  
Inflammatory Microenvironment

The development of tumors requires an initiator event, usually exposure to DNA damaging agents that cause genetic alterations such as gene mutations or chromosomal abnormalities, leading to deregulated cell proliferation. Although the mere stochastic accumulation of further mutations may cause tumor progression, it is now clear that an inflammatory microenvironment has a major tumor-promoting influence on initiated cells, in particular when a chronic inflammatory reaction already existed before the initiated tumor cell was formed. Moreover, inflammatory cells become mobilized in response to signals emanating from tumor cells. In both cases, the microenvironment provides signals that initiated tumor cells perceive by membrane receptors and transduce via downstream kinase cascades to modulate multiple cellular processes and respond with changes in cell gene expression, metabolism, and morphology. Cytokines, chemokines, and growth factors are examples of major signals secreted by immune cells, fibroblast, and endothelial cells and mediate an intricate cell-cell crosstalk in an inflammatory microenvironment, which contributes to increased cancer cell survival, phenotypic plasticity and adaptation to surrounding tissue conditions. Eventually, consequent changes in extracellular matrix stiffness and architecture, coupled with additional genetic alterations, further fortify the malignant progression of tumor cells, priming them for invasion and metastasis. Here, we provide an overview of the current knowledge on the composition of the inflammatory tumor microenvironment, with an emphasis on the major signals and signal-transducing events mediating different aspects of stromal cell-tumor cell communication that ultimately lead to malignant progression.

scholarly journals Interplay between BMPs and Reactive Oxygen Species in Cell Signaling and Pathology

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 534 ◽  
Author(s):  
Cristina Sánchez-de-Diego ◽  
José Antonio Valer ◽  
Carolina Pimenta-Lopes ◽  
José Luis Rosa ◽  
Francesc Ventura
Keyword(s):  
Reactive Oxygen Species ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Musculoskeletal Diseases ◽  
Current Knowledge ◽  
Reactive Oxygen ◽  
Membrane Receptors ◽  
Whole Body ◽  
Cell Physiology ◽  
Oxygen Species

The integration of cell extrinsic and intrinsic signals is required to maintain appropriate cell physiology and homeostasis. Bone morphogenetic proteins (BMPs) are cytokines that belong to the transforming growth factor-β (TGF-β) superfamily, which play a key role in embryogenesis, organogenesis and regulation of whole-body homeostasis. BMPs interact with membrane receptors that transduce information to the nucleus through SMAD-dependent and independent pathways, including PI3K-AKT and MAPKs. Reactive oxygen species (ROS) are intracellular molecules derived from the partial reduction of oxygen. ROS are highly reactive and govern cellular processes by their capacity to regulate signaling pathways (e.g., NF-κB, MAPKs, KEAP1-NRF2 and PI3K-AKT). Emerging evidence indicates that BMPs and ROS interplay in a number of ways. BMPs stimulate ROS production by inducing NOX expression, while ROS regulate the expression of several BMPs. Moreover, BMPs and ROS influence common signaling pathways, including PI3K/AKT and MAPK. Additionally, dysregulation of BMPs and ROS occurs in several pathologies, including vascular and musculoskeletal diseases, obesity, diabetes and kidney injury. Here, we review the current knowledge on the integration between BMP and ROS signals and its potential applications in the development of new therapeutic strategies.

scholarly journals TRPC channels: Dysregulation and Ca2+ Mishandling In Ischemic Heart Disease

2019 ◽  
Author(s):  
Debora Falcon ◽  
Isabel Galeano-Otero ◽  
Marta Martín-Bórnez ◽  
María Fernández-Velasco ◽  
Isabel Gallardo-Castillo ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Current Knowledge ◽  
Receptor Potential ◽  
Cardiac Cells ◽  
Membrane Receptors ◽  
Trpc Channels ◽  
Ischemia And Reperfusion ◽  
Sense And Respond ◽  
Transient Receptor

Transient receptor potential canonical (TRPC) channels are ubiquitously expressed in excitable and non-excitable cardiac cells where they sense and respond to a wide variety of physical and chemical stimuli. As other TRP, TRPC may form homo or heterotetrameric ion channel, and they can associate with other membrane receptors and ion channels to regulate intracellular calcium concentration. Dysfunctions of TRPC channels are involved in many types of cardiovascular diseases. Significant increase of the expression of different TRPC isoforms has been observed in different animal model of heart infarcts, and in vitro experimental model of ischemia and reperfusion. TRPC-mediated increase of the intracellular Ca2+ concentration seems required for the activation of signaling pathway that plays minor roles in the healthy heart, but they are more relevant for cardiac responses to ischemia, such as the activation of different factors of transcription and cardiac hypertrophy, fibrosis, and angiogenesis. In this review, we will highlight the current knowledge regarding TRPC implication in different cellular processes related to ischemia and reperfusion, and to heart infarction.

scholarly journals Virulence mechanisms used in the pathogenesis of periodontal diseases caused by Porphyromonas gingivalis

2020 ◽  
Vol 74 ◽  
pp. 247-259
Author(s):  
Michał Śmiga ◽  
Paulina Ślęzak ◽  
Klaudia Siemińska ◽  
Teresa Olczak
Keyword(s):  
Porphyromonas Gingivalis ◽  
Tooth Loss ◽  
Current Knowledge ◽  
Pathological Condition ◽  
Periodontal Diseases ◽  
Protoporphyrin Ix ◽  
Membrane Receptors ◽  
Two Component System ◽  
Fur Protein ◽  
Etiological Agents

Periodontal diseases are characterized by progressive inflammation that destroys the tooth-supporting tissues, leading to gum bleeding and tooth loss. Porphyromonas gingivalis is considered one of the main etiological agents responsible for the initiation and progression of chronic periodontitis. This gram-negative, anaerobic bacterium is a part of a multi-species oral biofilm. P. gingivalis does not have the full pathway of protoporphyrin IX synthesis, nor does it produce siderophores. Therefore, for survival and proliferation, it requires heme as a source of iron and protoporphyrin IX. In order to obtain heme, P. gingivalis uses a number of mechanisms that affect the ability of this bacterium to initiate a pathological condition. This review presents the current knowledge regarding the best-known and characterized systems involved in heme acquisition by P. gingivalis. We focused on processes occurring in the initial states of infection, where gingipain, hemagglutinins, and hemolysins play a crucial role. The mechanisms encoded by hmu, iht and hus operons, including proteins with hemophore-like properties, as well as TonB-dependent outer membrane receptors are described. We present their function and participation in the progression of the infection. In addition, we describe mechanisms produced by P. gingivalis and other periodontopathogens in synergistic processes promoting the growth and virulence of P. gingivalis. We also describe processes regulating iron and heme homeostasis, including the homolog of the Fur protein, the two-component system HaeSR, as well as the OxyR, SigH, and PgDps proteins.

scholarly journals Structural Basis for Vascular Endothelial Growth Factor Receptor Activation and Implications for Disease Therapy

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1673
Author(s):  
Faheem Shaik ◽  
Gary Cuthbert ◽  
Shervanthi Homer-Vanniasinkam ◽  
Stephen Muench ◽  
Sreenivasan Ponnambalam ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Kinase Inhibitors ◽  
Current Knowledge ◽  
Growth Factor Receptor ◽  
Receptor Activation ◽  
Membrane Receptors ◽  
Structural Basis ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Diverse Range

Vascular endothelial growth factors (VEGFs) bind to membrane receptors on a wide variety of cells to regulate diverse biological responses. The VEGF-A family member promotes vasculogenesis and angiogenesis, processes which are essential for vascular development and physiology. As angiogenesis can be subverted in many disease states, including tumour development and progression, there is much interest in understanding the mechanistic basis for how VEGF-A regulates cell and tissue function. VEGF-A binds with high affinity to two VEGF receptor tyrosine kinases (VEGFR1, VEGFR2) and with lower affinity to co-receptors called neuropilin-1 and neuropilin-2 (NRP1, NRP2). Here, we use a structural viewpoint to summarise our current knowledge of VEGF-VEGFR activation and signal transduction. As targeting VEGF-VEGFR activation holds much therapeutic promise, we examine the structural basis for anti-angiogenic therapy using small-molecule compounds such as tyrosine kinase inhibitors that block VEGFR activation and downstream signalling. This review provides a rational basis towards reconciling VEGF and VEGFR structure and function in developing new therapeutics for a diverse range of ailments.

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