scholarly journals Adenosine as a metabolic regulator of tissue function: production of adenosine by cytoplasmic 5'-nucleotidases.

2006 ◽  
Vol 53 (2) ◽  
pp. 269-278 ◽  
Author(s):  
Agnieszka Borowiec ◽  
Katarzyna Lechward ◽  
Kinga Tkacz-Stachowska ◽  
Andrzej C Składanowski

Adenosine is a product of complete dephosphorylation of adenine nucleotides which takes place in various compartments of the cell. This nucleoside is a significant signal molecule engaged in regulation of physiology and modulation of the function of numerous cell types (i.e. neurons, platelets, neutrophils, mast cells and smooth muscle cells in bronchi and vasculature, myocytes etc.). As part a of purinergic signaling system, adenosine mediates neurotransmission, conduction, secretion, vasodilation, proliferation and cell death. Most of the effects of adenosine help to protect cells and tissues during stress conditions such as ischemia or anoxia. Adenosine receptors and nucleoside transporters are targets for potential drugs in many pathophysiological situations. The adenosine-producing system in vertebrates involves a cascade dephosphorylating ATP and ending with 5'-nucleotidase (EC 3.1.3.5) localized either on the membrane or inside the cell. In this paper the cytoplasmic variants of 5'-nucleotidase are broadly characterized as well as their clinical relevance. The role of AMP-selective 5'-nucleotidase (cN-I) in the heart, skeletal muscle and brain is highlighted. cN-I action is crucial during ischemia and important for the efficacy of some nucleoside-based drugs and in the regulation of the substrate pool for nucleic acids synthesis. Inhibitors used in studying the roles of cytoplasmic and membrane-bound 5'-nucleotidases are also described.

2021 ◽  
Vol 11 ◽  
Author(s):  
P. Boknik ◽  
J. Eskandar ◽  
B. Hofmann ◽  
N. Zimmermann ◽  
J. Neumann ◽  
...  

This review presents an overview of cardiac A2A-adenosine receptors The localization of A2A-AR in the various cell types that encompass the heart and the role they play in force regulation in various mammalian species are depicted. The putative signal transduction systems of A2A-AR in cells in the living heart, as well as the known interactions of A2A-AR with membrane-bound receptors, will be addressed. The possible role that the receptors play in some relevant cardiac pathologies, such as persistent or transient ischemia, hypoxia, sepsis, hypertension, cardiac hypertrophy, and arrhythmias, will be reviewed. Moreover, the cardiac utility of A2A-AR as therapeutic targets for agonistic and antagonistic drugs will be discussed. Gaps in our knowledge about the cardiac function of A2A-AR and future research needs will be identified and formulated.


2001 ◽  
Vol 281 (5) ◽  
pp. F936-F947 ◽  
Author(s):  
Rajash K. Handa ◽  
Shelly E. Handa ◽  
Monica K. S. Elgemark

Receptor autoradiography revealed that angiotensin AT4 receptors were abundantly expressed in normal mammalian (mouse, rat, gerbil, guinea pig, rabbit) and avian (sparrow, chicken, turkey) kidneys and were more extensively distributed than previously reported (including proximal and distal segments of the nephron, interstitium, renal artery, vein, and ureter). Angiotensin AT4 receptors were generally found to be more abundant than angiotensin AT1 receptors in mammalian kidneys, whereas angiotensin AT(1—7) receptors were not detected in either mammalian or avian kidneys. Rats subjected to various chronic treatments were found to preferentially decrease kidney AT4 receptor density (furosemide, puromycin aminonucleoside, nitro-l-arginine methyl ester), decrease kidney AT1 receptor density (bilateral ureteral obstruction), or increase kidney AT1 receptor distribution in the inner medulla (water diuresis). These results indicate that the AT4 receptor can be expressed in numerous cell types within the normal kidney of several species. Furthermore, several models of renal dysfunction and injury have been identified that selectively alter kidney AT4 density and may potentially aid in elucidating the role of this novel angiotensin receptor system in renal function.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Mariagrazia Valentini ◽  
Alessia Piermattei ◽  
Gabriele Di Sante ◽  
Giuseppe Migliara ◽  
Giovanni Delogu ◽  
...  

A close relationship exists between gut microbiota and immune responses. An imbalance of this relationship can determine local and systemic immune diseases. In fact the immune system plays an essential role in maintaining the homeostasis with the microbiota that normally resides in the gut, while, at the same time, the gut microbiota influences the immune system, modulating number and function of effector and regulatory T cells. To achieve this aim, mutual regulation between immune system and microbiota is achieved through several mechanisms, including the engagement of toll-like receptors (TLRs), pathogen-specific receptors expressed on numerous cell types. TLRs are able to recognize ligands from commensal or pathogen microbiota to maintain the tolerance or trigger the immune response. In this review, we summarize the latest evidences about the role of TLRs expressed in adaptive T cells, to understand how the immune system promotes intestinal homeostasis, fights invasion by pathogens, and is modulated by the intestinal microbiota.


Author(s):  
Tian Tian ◽  
Markus Heine ◽  
Ioannis Evangelakos ◽  
Michelle Y. Jaeckstein ◽  
Nicola Schaltenberg ◽  
...  

Abstract Several studies suggest a role of extracellular adenine nucleotides in regulating adipose tissue functions via the purinergic signaling network. Metabolic studies in mice with global deletion of the purinergic receptor P2X7 on the C57BL/6 background indicate that this receptor has only a minor role in adipose tissue for diet-induced inflammation or cold-triggered thermogenesis. However, recent data show that a polymorphism (P451L) present in C57BL/6 mice attenuates P2X7 receptor function, whereas BALB/c mice express the fully functional P451 allele. To determine the potential role of P2rx7 under metabolic and thermogenic stress conditions, we performed comparative studies using male P2rx7 knockout (KO) and respective wild-type controls on both BALB/c and C57BL/6 backgrounds. Our data show that adipose P2rx7 mRNA levels are increased in obese mice. Moreover, P2rx7 deficiency results in reduced levels of circulating CCL2 and IL6 with a moderate effect on gene expression of pro-inflammatory markers in white adipose tissue and liver of BALB/c and C57BL/6 mice. However, P2X7 expression does not alter body weight, insulin resistance, and hyperglycemia associated with high-fat diet feeding on both genetic backgrounds. Furthermore, deficiency of P2rx7 is dispensable for energy expenditure at thermoneutral and acute cold exposure conditions. In summary, these data show that—apart from a moderate effect on inflammatory cytokines—P2X7 plays only a minor role in inflammatory and thermogenic effects of white and brown adipose tissue even on the BALB/c background.


Author(s):  
David A. Lovejoy ◽  
Téa Pavlović

AbstractIn humans, the teneurin gene family consists of four highly conserved paralogous genes that are the result of early vertebrate gene duplications arising from a gene introduced into multicellular organisms from a bacterial ancestor. In vertebrates and humans, the teneurins have become integrated into a number of critical physiological systems including several aspects of reproductive physiology. Structurally complex, these genes possess a sequence in their terminal exon that encodes for a bioactive peptide sequence termed the ‘teneurin C-terminal associated peptide’ (TCAP). The teneurin/TCAP protein forms an intercellular adhesive unit with its receptor, latrophilin, an Adhesion family G-protein coupled receptor. It is present in numerous cell types and has been implicated in gamete migration and gonadal morphology. Moreover, TCAP is highly effective at reducing the corticotropin-releasing factor (CRF) stress response. As a result, TCAP may also play a role in regulating the stress-associated inhibition of reproduction. In addition, the teneurins and TCAP have been implicated in tumorigenesis associated with reproductive tissues. Therefore, the teneurin/TCAP system may offer clinicians a novel biomarker system upon which to diagnose some reproductive pathologies.


2022 ◽  
pp. 1-12
Author(s):  
Christof Weinstock

In 2014, the membrane-bound protein CD59 became a blood group antigen. CD59 has been known for decades as an inhibitor of the complement system, located on erythrocytes and on many other cell types. In paroxysmal nocturnal haemoglobinuria (PNH), a stem cell clone with acquired deficiency to express GPI-anchored molecules, including the complement inhibitor CD59, causes severe and life-threatening disease. The lack of CD59, which is the only membrane-bound inhibitor of the membrane attack complex, contributes a major part of the intravascular haemolysis observed in PNH patients. This crucial effect of CD59 in PNH disease prompted studies to investigate its role in other diseases. In this review, the role of CD59 in inflammation, rheumatic disease, and age-related macular degeneration is investigated. Further, the pivotal role of CD59 in PNH and congenital CD59 deficiency is reviewed.


2014 ◽  
Vol 2 (1) ◽  
Author(s):  
Kirsty M. Danielson ◽  
Saumya Das

Extracellular vesicles (EV), including exosomes, microvesicles and apoptotic bodies, are released from numerous cell types and are involved in intercellular communication, physiological functions and the pathology of disease. They have been shown to carry and transfer a wide range of cargo including proteins, lipids and nucleic acids. The role of EVs in cardiac physiology and heart disease is an emerging field that has produced intriguing findings in recent years. This review will outline what is currently known about EVs in the cardiovascular system, including cellular origins, functional roles and utility as biomarkers and potential therapeutics.


2021 ◽  
pp. 1-9
Author(s):  
Shufen Zhang ◽  
Deshu Shang ◽  
Han Shi ◽  
Weiyu Teng ◽  
Li Tian

<b><i>Background:</i></b> Astrocytes are the most numerous cell types within the central nervous system, and many efforts have been put into determining the exact role of astrocytes in neuroprotection and repair after ischemic stroke. Although numerous studies have been done in recent years, there is still no thorough understanding of the exact function of astrocytes in the whole course of the stroke. <b><i>Summary:</i></b> According to the recent literature, there are many structures and factors that play important roles in the process of ischemic stroke, among which blood-brain barrier, various growth factors, gap junctions, AQP4, and glial scars have been studied most comprehensively, and all these factors are closely related to astrocytes. The role of astrocytes in ischemic stroke, therefore, can be analyzed more comprehensively. <b><i>Key Message:</i></b> The present review mainly summarized the current knowledge about astrocytes and their potential roles after ischemic stroke.


2003 ◽  
Vol 71 (3) ◽  
pp. 1481-1490 ◽  
Author(s):  
Françoise Porte ◽  
Aroem Naroeni ◽  
Safia Ouahrani-Bettache ◽  
Jean-Pierre Liautard

ABSTRACT Brucella species are gram-negative, facultative intracellular bacteria that infect humans and animals. These organisms can survive and replicate within a membrane-bound compartment inside professional and nonprofessional phagocytic cells. Inhibition of phagosome-lysosome fusion has been proposed as a mechanism for intracellular survival in both cell types. However, the molecular mechanisms and the microbial factors involved are poorly understood. Smooth lipopolysaccharide (LPS) of Brucella has been reported to be an important virulence factor, although its precise role in pathogenesis is not yet clear. In this study, we show that the LPS O side chain is involved in inhibition of the early fusion between Brucella suis-containing phagosomes and lysosomes in murine macrophages. In contrast, the phagosomes containing rough mutants, which fail to express the O antigen, rapidly fuse with lysosomes. In addition, we show that rough mutants do not enter host cells by using lipid rafts, contrary to smooth strains. Thus, we propose that the LPS O chain might be a major factor that governs the early behavior of bacteria inside macrophages.


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