scholarly journals Role of the phosphocreatine system on energetic homeostasis in skeletal and cardiac muscles

2014 ◽  
Vol 12 (1) ◽  
pp. 126-131 ◽  
Author(s):  
Lucas Guimarães-Ferreira

Adenosine triphosphate is the present energy currency in the body, and is used in various cellular and indispensable processes for the maintenance of cell homeostasis. The regeneration mechanisms of adenosine triphosphate, from the product of its hydrolysis – adenosine diphosphate – are therefore necessary. Phosphocreatine is known as its quickest form of regeneration, by means of the enzyme creatine kinase. Thus, the primary function of this system is to act as a temporal energy buffer. Nevertheless, over the years, several other functions were attributed to phosphocreatine. This occurs as various isoforms of creatine kinase isoforms have been identified with a distinct subcellular location and functionally coupled with the sites that generate and use energy, in the mitochondria and cytosol, respectively. The present study discussed the central and complex role that the phosphocreatine system performs in energy homeostasis in muscle cells, as well as its alterations in pathological conditions.

PARADIGMI ◽  
2009 ◽  
pp. 71-83
Author(s):  
Jean-Jacques Wunenburger

- Linguistic Sedimentation, and Bodily Inscription At present, we are exposed to an excessive offer of images, which raises a problem of assimilation. Subjects are increasingly passive, in ways that can border on pathological conditions. Yet, it is not so much a question of condemning this situation as of finding a way of re-symbolizing images, saving them from mere contemplation and inserting them in a process of contextualisation. Such a process requires an understanding of the role of the body and of the incorporation of images along the lines of Bachelard's intuition of the "resisting" nature of images. This raises the possibility of an education to images suited to the present age.Key words: Alienation, Education, Embodiment, Image, Informatics, Symbolisation.Parole chiave: Alienazione, Educazione, Immagine, Incorporazione, Informatica, Simbolizzazione.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 32-32
Author(s):  
Mateusz Adamiak ◽  
Arjun Thapa ◽  
Kamila Bujko ◽  
Valentina Pensato ◽  
Magdalena Kucia ◽  
...  

Background. Adenosine triphosphate (ATP) is an important nucleotide involved in intracellular energy transfer, but when released from activated cells into the extracellular space as extracellular ATP (eATP) it becomes a crucial mediator of the purinergic signaling network. Purinergic receptors for extracellular nucleotides (EXNs), expressed on the surface of all cells in the body, are represented by the P1, P2X, and P2Y receptor families, which are among the most abundant receptors in living organisms. Of all these receptors, the P2X receptor family is most highly specific for eATP signaling and consists of seven members (P2X1-7). We found that human and murine hematopoietic stem progenitor cells (HSPCs) highly express two members of this family, the P2X4 and P2X7 receptors. We recently reported that both are involved in optimal mobilization of HSPCs by activating Nlrp3 inflammasome (Leukemia 2020 Jun;34(6):1512-1523 and Stem Cell Rev Rep. 2019 Jun;15(3):391-403). We also reported that the P2X7 receptor expressed on the surface of HSPCs facilitates the homing and engraftment of HSPCs by increasing their responsiveness to SDF-1 gradients. Interestingly, it has been proposed that both receptors heterodimerize to exert optimal activity. Hypothesis. Since, the P2X4 and P2X7 receptors show several similar biological effects in non-hematopoietic cells, we became interested in the role of the P2X4 receptor in homing and engraftment of HSPCs.Materials and Methods. To test this hypothesis, we isolated SKL cells from P2X4-KO mice and tested them for migration in response to BM chemoattractants, including the major homing factor SDF-1. Next, we tested the short- and long-term homing of mouse BM cells after exposure to the P2X4-specific inhibitor PBS12054 in normal mice by evaluating the number of donor-derived PKH67-labeled BMMNCs and CFU-GM clonogenic progenitors isolated from recipient mouse BM 24 hours after transplantation as well as the number of day-12 colony-forming units in spleen (CFU-S) and day-12 CFU-GM clonogenic progenitors. These data were confirmed in transplant studies employing P2X4-KO bone marrow cells. In parallel, we also evaluated the recovery kinetics of leukocytes and blood platelets in the PB of transplanted animals. Finally, we also perturbed P2X4 expression in transplanted mice with PBS12054 and studied the effect on homing and engraftment of normal BM cells, as described above. Results. We found that P2X4-KO mouse HSPCs have a defect in migration in response to BM chemoattractants involved in BM homing, including the major homing factor SDF-1 as well as the supportive factors S1P and eATP. Perturbation of P2X4 expression on the surface of HSPCs led to significant defective homing and engraftment of HSPCs. Moreover, inhibition of P2X4 in the recipient mouse BM microenvironment had a similar effect. Conclusions. We identified for the first time the role of eATP-P2X4 signaling in the homing and engraftment of HSPCs. To explain this result, we conclude that the eATP-P2X4 axis is, like the eATP-P2X7 axis, a potent activator of Nlrp3 inflammasomes and that defective eATP-P2X4 signaling impairs the role of purinergic signaling and the Nlrp3 inflammasome in homing and engraftment. Moreover, our results show a similar homing and engraftment phenotype for P2X4-KO mice as that seen in P2X7-KO animals, which provides functional support for the proposed dimerization of P2X7 with P2X4 receptors and the necessary presence of both receptors for optimal function. This question is currently being addressed in our laboratory by employing the fluorescence resonance energy transfer (FRET) technique. Finally, we provide additional evidence that, in addition to SDF-1 and S1P, eATP and purinergic signaling involving P2X4 and P2X7 receptors is an important and underappreciated regulator of HSPC trafficking and a potential target for molecular optimization of both processes. Disclosures No relevant conflicts of interest to declare.


2012 ◽  
Vol 302 (11) ◽  
pp. R1235-R1249 ◽  
Author(s):  
Sara Stridh ◽  
Fredrik Palm ◽  
Peter Hansell

The glycosaminoglycan (GAG) hyaluronan (HA) is recognized as an important structural component of the extracellular matrix, but it also interacts with cells during embryonic development, wound healing, inflammation, and cancer; i.e., important features in normal and pathological conditions. The specific physicochemical properties of HA enable a unique hydration capacity, and in the last decade it was revealed that in the interstitium of the renal medulla, where the HA content is very high, it changes rapidly depending on the body hydration status while the HA content of the cortex remains unchanged at very low amounts. The kidney, which regulates fluid balance, uses HA dynamically for the regulation of whole body fluid homeostasis. Renomedullary HA elevation occurs in response to hydration and during dehydration the opposite occurs. The HA-induced alterations in the physicochemical characteristics of the interstitial space affects fluid flux; i.e., reabsorption. Antidiuretic hormone, nitric oxide, angiotensin II, and prostaglandins are classical hormones/compounds involved in renal fluid handling and are important regulators of HA turnover during variations in hydration status. One major producer of HA in the kidney is the renomedullary interstitial cell, which displays receptors and/or synthesis enzymes for the hormones mentioned above. During several kidney disease states, such as ischemia-reperfusion injury, tubulointerstitial inflammation, renal transplant rejection, diabetes, and kidney stone formation, HA is upregulated, which contributes to an abnormal phenotype. In these situations, cytokines and other growth factors are important stimulators. The immunosuppressant agent cyclosporine A is nephrotoxic and induces HA accumulation, which could be involved in graft rejection and edema formation. The use of hyaluronidase to reduce pathologically overexpressed levels of tissue HA is a potential therapeutic tool since diuretics are less efficient in removing water bound to HA in the interstitium. Although the majority of data describing the role of HA originate from animal and cell studies, the available data from humans demonstrate that an upregulation of HA also occurs in diabetic kidneys, in transplant-rejected kidneys, and during acute tubular necrosis. This review summarizes the current knowledge regarding interstitial HA in the role of regulating kidney function during normal and pathological conditions. It encompasses mechanistic insights into the background of the heterogeneous intrarenal distribution of HA; i.e., late nephrogenesis, its regulation during variations in hydration status, and its involvement during several pathological conditions. Changes in hyaluronan synthases, hyaluronidases, and binding receptor expression are discussed in parallel.


2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Patricia Fernández-Riejos ◽  
Souad Najib ◽  
Jose Santos-Alvarez ◽  
Consuelo Martín-Romero ◽  
Antonio Pérez-Pérez ◽  
...  

Adipose tissue is an active endocrine organ that secretes various humoral factors (adipokines), and its shift to production of proinflammatory cytokines in obesity likely contributes to the low-level systemic inflammation that may be present in metabolic syndrome-associated chronic pathologies such as atherosclerosis. Leptin is one of the most important hormones secreted by adipocytes, with a variety of physiological roles related to the control of metabolism and energy homeostasis. One of these functions is the connection between nutritional status and immune competence. The adipocyte-derived hormone leptin has been shown to regulate the immune response, innate and adaptive response, both in normal and pathological conditions. The role of leptin in regulating immune response has been assessed in vitro as well as in clinical studies. It has been shown that conditions of reduced leptin production are associated with increased infection susceptibility. Conversely, immune-mediated disorders such as autoimmune diseases are associated with increased secretion of leptin and production of proinflammatory pathogenic cytokines. Thus, leptin is a mediator of the inflammatory response.


1995 ◽  
Vol 73 (10) ◽  
pp. 1899-1911 ◽  
Author(s):  
A. P. Farrell ◽  
J. A. Johansen

This study surveyed and compared vasoactive responses of isolated coronary vessels from steelhead trout (Oncorhynchus mykiss), rainbow trout (also O. mykiss), and spiny dogfish (Squalus acanthias). The purpose of the investigation was twofold: to identify vasoactive controls that were possibly mediated by the vascular endothelium and to highlight the possible consequences on vasoactivity of the coronary lesions known to be present in the main coronary of salmonids but not dogfish. The test substances included acetylcholine, adenosine, adenosine triphosphate, adenosine diphosphate, serotonin, thrombin, bradykinin, prostaglandin F2α, prostaglandin I2, prostaglandin E2, and the fatty acids arachidonic acid, docosahexaenoic acid, and eicosapentaenoic acid. Acetylcholine, adenosine, adenosine triphosphate, adenosine diphosphate and prostaglandin F2α typically produced contractions. Use of endothelial removal techniques and antagonists failed to reveal any relaxations that might involve the endothelium. Thrombin and bradykinin had no vasoactivity. Serotonin, prostaglandin I2, and prostaglandin E2 produced relaxations that were not mediated by the endothelium. The powerful relaxations observed with prostaglandin I2 and prostaglandin E2 and the powerful contractions observed with prostaglandin F2α suggest a major role of prostanoids in coronary vasoactivity in fish. These prostanoid-mediated mechanisms, in addition to the previously demonstrated powerful contractions with endothelin-1, point to an important role for the endothelium. No major qualitative or quantitative differences in vasoactivity could be related to differences in coronary lesion severity.


Author(s):  
Paulina Niedźwiedzka-Rystwej ◽  
Dominika Bębnowska ◽  
Roman Kołacz ◽  
Wiesław Deptuła

Research on the health of mammals invariably shows how dynamic immunology is and how the role of many elements and immune processes of the macroorganism, developed in the process of evolution in protecting against threats, including infections, is changing. Among these elements conditioning the homeostasis of the macroorganism are mitochondria, PRR receptors (pattern recognition receptors) and the phenomenon of autophagy. In the context of physiological and pathological states in the body, mitochondria perform various functions. The primary function of these organelles is to produce energy in the cell, but on the other hand, they are heavily involved in various cellular processes, including ROS production and calcium homeostasis. They are largely involved in the activation of immune mechanisms during infectious and non-infectious conditions through mtDNA and the mitochondrial MAVS protein. Mitochondrial involvement has been also determined in PRR-related mechanisms as mtDNA has the ability to directly stimulate TLRs. On the other hand, mitochondria are also associated with apoptotic cell death and autophagy.


2019 ◽  
pp. 328-349
Author(s):  
Pavel Pavlovich Zagoskin

The principal possibility of nonspecific energy expenditure at all stages of the transformation of nutrients in the body is demonstrated. These stages include the processing of food in the mouth, digestion, absorption, interaction with the intestinal micro biome, and interstitial metabolic processes. Particular attention is paid to the role of nonspecific energy expenditure of the body in the regulation of body mass. The data on the pivotal role of reducing nonspecific energy expenditure in the development of obesity and associated pathological conditions are presented. The prospects for using uncouples of oxidative phosphorylation, fatty acids, carnitine, bile acids, sarcolipin and a number of other substances as regulators of the nonspecific energy expenditure and potential means of preventing and treating obesity are analyzed.


2021 ◽  
Vol 12 ◽  
Author(s):  
Kasiphak Kaikaew ◽  
Aldo Grefhorst ◽  
Jenny A. Visser

Excessive fat accumulation in the body causes overweight and obesity. To date, research has confirmed that there are two types of adipose tissue with opposing functions: lipid-storing white adipose tissue (WAT) and lipid-burning brown adipose tissue (BAT). After the rediscovery of the presence of metabolically active BAT in adults, BAT has received increasing attention especially since activation of BAT is considered a promising way to combat obesity and associated comorbidities. It has become clear that energy homeostasis differs between the sexes, which has a significant impact on the development of pathological conditions such as type 2 diabetes. Sex differences in BAT activity may contribute to this and, therefore, it is important to address the underlying mechanisms that contribute to sex differences in BAT activity. In this review, we discuss the role of sex hormones in the regulation of BAT activity under physiological and some pathological conditions. Given the increasing number of studies suggesting a crosstalk between sex hormones and the hypothalamic-pituitary-adrenal axis in metabolism, we also discuss this crosstalk in relation to sex differences in BAT activity.


1988 ◽  
Vol 255 (5) ◽  
pp. F811-F822 ◽  
Author(s):  
D. B. Young

Aldosterone is part of a complex system that regulates plasma potassium concentration by affecting the renal excretion of the ion as well as its distribution within the body. Because there are other components of the system, it has been difficult to determine the physiological significance of aldosterone in potassium regulation by attempting to study the hormone's effects in isolation. In this presentation a quantitative analysis of the potassium control system is used to provide information concerning the physiological role of aldosterone in potassium regulation under normal and pathological conditions, as well as during pharmacological interventions.


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