Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Paracrine signalling wikipedia , lookup
Lipid signaling wikipedia , lookup
Magnesium in biology wikipedia , lookup
Mitochondrial replacement therapy wikipedia , lookup
Lactate dehydrogenase wikipedia , lookup
Mitochondrion wikipedia , lookup
Evolution of metal ions in biological systems wikipedia , lookup
Signal transduction wikipedia , lookup
Metalloprotein wikipedia , lookup
Annals of R.S.C.B., Vol. XXI, Issue 1, 2016, pp. 1 – 6 Received 12 January 2016; accepted 21 December 2016. doi: 10.ANN/RSCB-2016-0001:RSCB Considerations on the structures involved in the control of transmission mechanism mediated of calcium pulses ANTONELLA CHEŞCĂ(1), TIM SANDLE(2), GELLERT ATTILA GYURKA(3) 1,3 Department of Basic, Preventive and Clinical Sciences, Faculty of Medicine, „Transilvania” University of Braşov, Romania 2 Head of Microbiology, BPL, United Kingdom *Corresponding author Antonella Chescǎ, Ph.D. Lecturer MD, Department of Basic, Preventive and Clinical Sciences, Faculty of Medicine, „Transilvania” University of Braşov, 56 Nicolae Bălcescu Street, 500019, Braşov, Romania; Phone +40268412185, Email: [email protected] Keywords. Calcium transport mechanisms, signaling, structures, illness, calcium ions, physiology Summary studies, it is there is a difference between the actual concentration of calcium ions in intracellular and extracellular space. This determines the cellular penetration and diffusion. From this perspective, the flux of calcium ions involved in the activity of intracellular processes are carried out according to the principle that involves the penetration of ionic calcium into the cells, via channels, through the diffusion process that follows the concentration gradient direction (Bianchi et.al., 2004). The level of calcium ions in the cell, at abnormal values, is determined by defining it as a second messenger, serving as a mediator of external signals involving hormones, neurotransmitters and growth factors. Here the calcium ion interferes with the transmission of stimuli arising from the cell surface. The external signals are detected up by receivers connected to the various translation mechanisms responsible for increasing the intracellular calcium ion concentration and combining this with an intracellular receptor level - troponin C and calmodulin - by activating a series of intracellular processes. This mode of transmission can be influenced by other secondary messengers like cAMP or diacylglycerol. These can lead to an adjustment to the translation Given the importance of calcium for good functioning of the body and knowing its involvement in signaling mechanisms and intercellular transport (which involves mechanisms related to the translation of transmembrane signals), the study outlined combines theoretical and practical data relating to the these processes. Theoretical information is supported by data collected from medical practice. Here attention is paid to the body structures involved in pathologies and changes that have occurred due to imbalance of calcium ions within different structures and at the level of cellular ultrastructure. With the presentation of the structural components, these bring into focus various kinds of diseases associated with calcium ion pulses. Introduction According to the current information, the level of calcium in the body is around 2% of body weight. Of this total, 99% of calcium is contained within bone and the remainder in the body is in the form of calcium ions bound to the anion or protein. It is known, however, that some calcium ions are located on the cell membrane surface. In the context, it is important to mention that, according to The Romanian Society for Cell Biology ©, Annals of R. S. C. B., Vol. XXI, Issue 1, 2016, Antonella Cheşcă, pp. 1 – 6 1 Annals of R.S.C.B., Vol. XXI, Issue 1, 2016, pp. 1 – 6 Received 12 January 2016; accepted 21 December 2016. doi: 10.ANN/RSCB-2016-0001:RSCB mechanisms, the expulsion of intracellular calcium ion or causing receptors that serve as mediators of cation action (Hüser et.al., 2000). Moreover, there are cells that react to depolarization by increasing intracellular ionic calcium. Here calcium mobilization processes are voltage dependent (Krumschnabel et.al., 2014). It is widely thought that the main source of calcium ions at the extracellular level are the sarcoplasmic reticulum and in the mitochondria. Calcium ion influx from outside is balanced by a corresponding outflow. As this occurs, every cell membrane has a constant kinetic. Normally, this has implications for maintaining calcium homeostasis. Studies have shown how the membrane systems have an adjustment-set point characteristic, which is the where the concentration of calcium ions in the currents entering and those leaving are in perfect balance. Further studies have shown that the mitochondrial point of adjustment is higher compared to the control within the sarcolemma and sarcoplasmic reticulum (Levy et.al., 2005). With the immobilization of ionic calcium through voltage-dependent process, depolarization of the cell membrane increases the internal concentration of calcium ions through the opening of voltage-dependent calcium channels. These are located at the cell membrane ((Krumschnabel et.al., 2014). Calcium channels play an important role in smooth muscle, synaptic terminals, heart, adrenal chromaffin cells of, insulinsecretors cells ((Hüser et.al., 2000). Calcium ion flow through such ion channels is modulated by the secondary messenger cyclic adenosine monophosphate (cAMP). This increases the possibility for each channel to be opened when a membrane depolarization occurs (Fritzen et.al., 2000). Depolarization causes calcium deposits also to mobilize. For asset-dependent receptors, it is assumed that there is an infinite number of external signals acting through mobilizing calcium receptor ((Bianchi et.al., 2004). Maintaining a high concentration of calcium in the cytosol, as well as the removal of this ion in the cytosol, may be achieved by activating and involving calcium ions. Here it is the calcium-calmodulin (calciummodulated protein) complex that activates cationic pumps. Calmodulin functions as a multifunctional intermediate messenger protein. It transduces calcium signals through the binding of calcium ions. These are then modified through the interactions with differing target proteins. It is important to study the mechanisms of muscle contraction relating to fibers in striated muscle tissue. With this it is useful to note the presence of lactic acid and lactate, as well as the final product. This is due to glycolysis evoked changes occuring at the cellular level, such as the shift from aerobic to anaerobic in presence of ATP, and oxygen. Here studies have shown that muscle lactate is exported to the liver to facilitate clearance. This indicates a dynamic mobilization and utilization of lactate during a cycle of muscle contraction (Park et.al., 2015). Numerous effects of ionic calcium into the cell are connected with synergy and antagonism, with other second messengers. From this standpoint, cAMP and diacylglycerol play an important role in modulating various aspects especially in relation to the calcium signal transmission. In some cells, the modulation of calcium ions seems the only function of cAMP and diacylglycerol. Thus in striated muscle sarcoplasmic reticulum, calcium release from troponin C causes contraction and calmodulin release from the fosforilazkinazei, resulting in stimulation of glycogen degradation. This results in the energy required striated muscle contraction (Bowtell et.al., 2007). In the myocardium, cAMP increases the calcium current through ion channels. Protein kinase A, through which phosphorylates fosfolambanul stimulates calcium from the sarcoplasmic reticulum pump, thereby follows contraction. However, phosphorylated cAMP troponin I and troponin C affinity for calcium decreases, causing muscle relaxation (Fritzen et.al., 2000). Considered to be the result of lack of oxygen in skeletal muscle contraction, glycolytic lactate production is formed and it operates under aerobic conditions. The concepts of "cell to cell" and "intracellular lactate transfer" describe the roles of lactate in The Romanian Society for Cell Biology ©, Annals of R. S. C. B., Vol. XXI, Issue 1, 2016, Antonella Cheşcă, pp. 1 – 6 2 Annals of R.S.C.B., Vol. XXI, Issue 1, 2016, pp. 1 – 6 Received 12 January 2016; accepted 21 December 2016. doi: 10.ANN/RSCB-2016-0001:RSCB the development of oxidative reactions and gluconeogenic substrates as well as in cell signaling (Yaniv Y et.al., 2005). Examples of "cell-cell" exchanges includes exchanges of glycolytic lactate between white and red fiber-oxidation in a bed of moss working between skeletal muscles and the heart; and net lactate release of tissues; and gluconeogenesis. With these, mitochondria are involved in setting the necessary slope density for mitochondrial cells as cardiomyocytes (Yaniv Y et.al., 2008). Measurements observation on working arteriovenous show differences between cardiac and skeletal muscle structures. Nuclear Magnetic Resonance (NMR) spectral analysis of these tissues shows that lactate is formed in cells in vivo (Makrecka-Kuka et.al., 2015). The intracellular lactate shuttle (ILS) is a necessary component of the mechanism described above. Lactate "cell-cell" (CCLS) as provided in the gap and lactate vascular network can be retrieved and used in highly oxidative cells; or skeletal and cardiac muscle fibers; or hepatocytes. ILS highlights the role of mitochondrial redox proton creation and anion lactate showing slopes needed to eliminate oxidative mitochondrial reticulum useful lactate during exercise (Gibala et.al., 2002). This hypothesis was initially supported by direct measurement of the lactate oxidation in isolated mitochondria and conclusions regarding the existence of mitochondrial monocarboxylate transporters (mMCT) and lactate dehydrogenase (mLDH) were drawn. Subsequently, the presence of complex mitochondrial lactate oxidation (composed of mMCT1, CD147 (basigin) mLDH, and cytochrome oxidase (COX)) was discovered and shown to have a role in supporting the presence of ILS (Gnaiger, 2009). Lactate is capable of upregulating MCT1 and COX gene and protein expression (Brooks, 2002). The findings present allow us to understand how lactate production during exercise is a physiological signal to activate a vast network of transcription, affecting MCT1 protein expression and biogenesis of mitochondrial. This explains how exercise enhances the ability lactate clearance by oxidation (Hashimoto et.al., 2008). According to some studies, it has been observed that sepsis and septic shock are associated with hyperlactatemia (sepsisassociated hyperlactataemia (SAHL)). SAHL is a strong independent predictor of mortality and the presence and progression is highly valued by physicians in order to define a very high-risk population. Furthermore, laboratory applications have shown that SAHL is a marker of tissue hypoxia (Garcia-Alvarez et.al., 2014). Issues involving ionic calcium and other compounds acts as biopharmaceutical mechanisms and biomolecular signals of diseases. Thus modicările ultrastructural cellular results of transmembrane transport involving calcium and the systems of cell signaling, can be found in studies using randomized, double-blind, sets of patients; and these correlate with disease patterns (Donnino et.al., 2015). Materials and methods In the context of the calcium mechanism involving transmembrane transport and cellular signaling, this paper presents structures of the modifications of calcium in the body. The structures presented are from bodies involved in pathologies. Here it is noted that striated muscle plays an important role as an energy producer in the form of ATP. Cardiac muscle is also influenced by regulating calcium proper functionality. Changes in calcium concentration has consequences for the functionality of the heart and blood vessels. Also, in the context of good functionality of the heart ,pathologies related to imbalances seriously affect organs such as the liver, which is a manufacturer of calcium in the form of ATP. From microscopic preparations we can observe structural details such as mitochondria in binucleate hepatocytes. Given that the diseases that affect internal organs in the context of this paper, preparations of smooth muscle are presented. Here it is noted that with the uterine smooth muscle it is important to have a level of The Romanian Society for Cell Biology ©, Annals of R. S. C. B., Vol. XXI, Issue 1, 2016, Antonella Cheşcă, pp. 1 – 6 3 Annals of R.S.C.B., Vol. XXI, Issue 1, 2016, pp. 1 – 6 Received 12 January 2016; accepted 21 December 2016. doi: 10.ANN/RSCB-2016-0001:RSCB optimal calcium necessary for optimal contractions, especially during labor. With the analysis of microscopic preparations these were prepared using conventional histological techniques and using typical and special stains. Microscopic preparations were examined using objective x10 and x40 magnifying power and Nikon microscopes. Results and discussions Fig.2. Striated muscle tissue Ferric Hematoxylin Heidenhein Staining x20, Longitudinal section. The data presented thus far is associated with theoretical information. In order to show physiological effects, outlined below are played structural images of organs involved in calcium transport mechanisms, storage and filing, for the cation. The first figure presented restores the structural skeletal muscle fibers. Striated muscle that is the subject of exercise and the relaxation mechanism of contraction, releases lactate or lactic acid following the cessation of the exercise. In addition to the numerous mitochondria is striated muscle, which produces energy in the form of the transporter adenosine triphosphate (figure 1). Figure three is of the uterus, showing the structural, functional and timing of specific glands and the myometrium, where muscle fibers are shown with a characteristic appearance. (figure 3) Fig.3. Uterus. H&E Staining x20. section. Longitudinal Figure four displays the structural aspect of the heart, where the cardiac muscle tissue with a specific type of striated scalariform disc Eberth, interleaves. (figure 4) Fig.1. Striated muscle tissue H&E Staining x20. Longitudinal section. Skeletal muscle fibers are also shown in the second figure, in longitudinal section, using Heidenhein staining, a trichrome stain. (figure 2) The Romanian Society for Cell Biology ©, Annals of R. S. C. B., Vol. XXI, Issue 1, 2016, Antonella Cheşcă, pp. 1 – 6 4 Annals of R.S.C.B., Vol. XXI, Issue 1, 2016, pp. 1 – 6 Received 12 January 2016; accepted 21 December 2016. doi: 10.ANN/RSCB-2016-0001:RSCB Fig. 4. Heart. H&E Staining x20. Longitudinal section. Fig. 6. Liver. Silver impregnation, Gomori Staining x20. Longitudinal section. The following figure shows, in detail, binucleate hepatocytes cords and visible points of mitochondria throughout the cytoplasm. Hepatocytes constitute around 7085% of the liver's mass. The liver is an organ within which energy is stored in the form of the nucleoside adenosine triphosphate (ATP). In this context, mitochondria play an important role in this energy retentive process. (figure 5) Knowing that the mechanisms described in the introduction are reflected on vascular structures or the artery and vein, the following figure shows the two types of blood vessels. The observation is concerned with the structural difference. The issues presented are comparable to the skeletal muscles and other organs involved in the mechanism described in the introduction of this paper. (figure 7) Fig. 5. Liver. H&E Staining x20. Longitudinal section. Fig.7. Liver. Goldner Longitudinal section. The structural appearance of the liver as a whole is shown in the figure below, using a special color suggestive. Here it can be observed, both hepatocytes cords and elements of the Kiernan space, the interlobular space in the liver. (figure 6) Szekely Staining x20. Conclusions The importance of the contribution of this study has been to explore the interaction of calcium ions on the proper functions of the body. Most notably this is through the involvement of calcium ions with intracellular transport mechanisms and control of the transmembrane role in translating The Romanian Society for Cell Biology ©, Annals of R. S. C. B., Vol. XXI, Issue 1, 2016, Antonella Cheşcă, pp. 1 – 6 5 Annals of R.S.C.B., Vol. XXI, Issue 1, 2016, pp. 1 – 6 Received 12 January 2016; accepted 21 December 2016. doi: 10.ANN/RSCB-2016-0001:RSCB resolution respirometry and fluorometry, Methods Enzymol., 2014, 542:163-81. Levy C., Ter Keurs H.E., Yaniv Y., Landesberg A., The sarcomeric control of energy conversion, Ann N Y Acad Sci., 2005, 1047:219-31. Makrecka-Kuka M., Krumschnabel G., Gnaiger E., High-Resolution Respirometry for Simultaneous Measurement of Oxygen and Hydrogen Peroxide Fluxes in Permeabilized Cells, Tissue Homogenate and Isolated Mitochondria, Biomolecules, 2015, 29;5(3):1319-38. Park J.M., Josan S., Mayer D., Hurd R.E., Chung Y., Bendahan D., Spielman D.M., Jue T., Hyperpolarized 13C NMR observation of lactate kinetics in skeletal muscle, J Exp Biol., 2015, 218(Pt 20):3308-18. Yaniv Y., Sivan R., Landesberg A., Analysis of hystereses in force length and force calcium relations, Am J Physiol Heart Circ Physiol., 2005, 288(1):H389-99. Yaniv Y., Stanley W.C., Saidel G.M., Cabrera M.E., Landesberg A., The role of Ca2+ in coupling cardiac metabolism with regulation of contraction: in silico modeling, Ann N Y Acad Sci., 2008, 1123:69-78. transmembrane signals. Studies are ongoing to ascertain these functions in more detail. In the context of the structural issues presented, this study could be continued and extended using modern biomolecular analysis. This would allow further exploration of the important issues raised. References Bianchi K, Rimessi A, Prandini A, Szabadkai G, Rizzuto R., Calcium and mitochondria: mechanisms and functions of a troubled relationship, Biochim Biophys Acta., 2004, 6;1742(1-3):119-31. Bowtell J.L., Marwood S., Bruce M., ConstantinTeodosiu D., Greenhaff P.L., Tricarboxylic acid cycle intermediate pool size: functional importance for oxidative metabolism in exercising human skeletal muscle. Sports Med., 2007, 37(12):107188. Brooks G.A., Lactate shuttles in nature, Biochem Soc Trans., 2002, 30(2):258-64. Donnino M.W., Mortensen S.J., Andersen L.W., Chase M., Berg K.M., Balkema J., Radhakrishnan J., Gazmuri R.J., Liu X., Cocchi M.N., Ubiquinol (reduced Coenzyme Q10) in patients with severe sepsis or septic shock: a randomized, doubleblind, placebo-controlled, pilot trial, Crit Care., 2015, Jul 1;19:275. Fritzen A.M., Lundsgaard A.M., Jeppesen J., Christiansen M.L., Biensø R., Dyck J.R., Pilegaard H,, Kiens B., 5'-AMP activated protein kinase α2 controls substrate metabolism during post-exercise recovery via regulation of pyruvate dehydrogenase kinase 4, J Physiol., 2015, 1;593(21):4765-80. Garcia-Alvarez M., Marik P., Bellomo R., Sepsisassociated hyperlactatemia, Crit Care., 2014, 9;18(5):503. Gibala M.J., González-Alonso J., Saltin B., Dissociation between muscle tricarboxylic acid cycle pool size and aerobic energy provision during prolonged exercise in humans, J Physiol., 2002 1;545(Pt 2):705-13. Gnaiger E., Capacity of oxidative phosphorylation in human skeletal muscle: new perspectives of mitochondrial physiology, Int J Biochem Cell Biol., 2009,41(10):1837-45. Hashimoto T., Brooks G.A., Mitochondrial lactate oxidation complex and an adaptive role for lactate production, Med Sci Sports Exerc., 2008,40(3):48694. Hüser J, Blatter L.A., Sheu S.S., Mitochondrial calcium in heart cells: beat-to-beat oscillations or slow integration of cytosolic transients?, J Bioenerg Biomembr., 2000,32(1):27-33. Krumschnabel G., Eigentler A., Fasching M., Gnaiger E., Use of safranin for the assessment of mitochondrial membrane potential by high- The Romanian Society for Cell Biology ©, Annals of R. S. C. B., Vol. XXI, Issue 1, 2016, Antonella Cheşcă, pp. 1 – 6 6