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133 results on '"LADILOV, Y."'

1. Asprosin as a potential new paracrine regulator in the heart

Author

Beck, C, primary, Morcos, Y A T, additional, Piekarek, N, additional, Juette, T, additional, Gerken, A, additional, Lubomirov, L T, additional, Schroeter, M M, additional, Winkelmann, A, additional, Grisk, O, additional, Albes, J M, additional, Sengle, G, additional, Ladilov, Y, additional, and Pryymachuk, G, additional

Published
2024
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8. Cardioprotective effects of KB-R7943: a novel inhibitor of the reverse mode of Na+/Ca2+ exchanger

Author

Ladilov, Y. Haffner, S., Balser-Schafer, C., Maxeiner, H., and Piper, H.M.

Subjects
Heart cells -- Research, Rats -- Physiological aspects, Calcium in the body -- Physiological aspects, Ischemia -- Research, Cytosol -- Research, Sodium in the body -- Physiological aspects, Biological sciences
Abstract

Research was conducted to examine the cardioprotective effects of KB-R7943 (KB) in isolated rat cardiomyocytes exposed to 80 minutes of simulated ischemia and 15 minutes of reoxygenation. The objective was to investigate, on the cellular level, the effects ofKB on cytosolic ion homeostatis during ATP depletion. Results indicate that the treatment of KB during anoxia effectively inhibits CA2+ overload and attenuates reoxygenation-induced injury of cardiomyocytes.

Published
1999

13. Modulation of early [[Ca.sup.2+]].sub.i] rise in metabolically inhibited endothelial cells by xestospongin C

Author

SCHAFER, M., BAHDE, D., BOSCHE, B., LADILOV, Y., SCHAFER, C., PIPER, H.M., and NOLL, T.

Subjects
Endothelium -- Physiological aspects, Calcium channels -- Physiological aspects, Hypoxia -- Physiological aspects, Ischemia -- Physiological aspects, Biological sciences
Abstract

Schafer, M., D. Bahde, B. Bosche, Y. Ladilov, C. Schafer, H. M. Piper, and T. Noll. Modulation of early [[Ca.sup.2+]].sub.i] rise in metabolically inhibited endothelial cells by xestospongin C. Am J Physiol Heart Circ Physiol 280: H1002-H1010, 2001.--When energy metabolism is disrupted, endothelial cells lose [Ca.sup.2+] from endoplasmic reticulum (ER) and the cytosolic [Ca.sup.2+] concentration ([[Ca.sup.2+]].sub.i]) increases. The importance of glycolytic energy production and the mechanism of [Ca.sup.2+] loss from the ER were analyzed. Endothelial cells from porcine aorta in culture and in situ were used as models. 2-Deoxy-D-glucose (2-DG, 10 mM), an inhibitor of glycolysis, caused an increase in [[Ca.sup.2+]].sub.i] (measured with fura 2) within 1 min when total cellular ATP contents were not yet affected. Stimulation of oxidative energy production with pyruvate (5 mM) did not attenuate this 2-DG-induced rise of [[Ca.sup.2+]].sub.i], while this maneuver preserved cellular ATP contents. The inhibitor of ER-[Ca.sup.2+]-ATPase, thapsigargin (10 nM), augmented the 2-DG-induced rise of [[Ca.sup.2+]].sub.i]. Xestospongin C (3 [micro]M), an inhibitor of D-myo-inositol 3-phosphate [Ins(3)P]-sensitive ER-[Ca.sup.2+] release, abolished the rise. The results demonstrate that the ER of endothelial cells is very sensitive to glycolytic metabolic inhibition. When this occurs, the ER [Ca.sup.2+] store is discharged by opening of the Ins(3)P-sensitive release channel. Xestospongin C can effectively suppress the early [[Ca.sup.2+]].sub.i] rise in metabolically inhibited endothelial cells. D-myo-inositol 3-phosphate-sensitive [Ca.sup.2+] release; ischemia; hypoxia; cytosolic [Ca.sup.2+] concentration

Published
2001

14. Inhibition of NHE protects reoxygenated cardiomyocytes independently of anoxic [Ca.sup.2+] overload and acidosis

Author

SCHAFER, C., LADILOV, Y. V., SCHAFER, M., and PIPER, H. M.

Subjects
Heart cells -- Physiological aspects, Hypoxia -- Physiological aspects, Acidosis -- Physiological aspects, Hydrogen-ion concentration -- Physiological aspects, Calcium in the body -- Physiological aspects, Ischemia -- Physiological aspects, Biological sciences
Abstract

Schafer, C., Y. V. Ladilov, M. Schafer, and H. M. Piper. Inhibition of NHE protects reoxygenated cardiomyocytes independently of anoxic [Ca.sup.2+] overload and acidosis. Am J Physiol Heart Circ Physiol 279: H2143-H2150, 2000.--We investigated the question of whether inhibition of the [Na.sup.+]/[H.sup.+] exchanger (NHE) during ischemia is protective due to reduction of cytosolic [Ca.sup.2+] accumulation or enhanced acidosis in cardiomyocytes. Additionally, the role of the [Na.sup.+]-[MATHEMATHICAL EXPRESSION] symporter (NBS) was investigated. Adult rat cardiomyocytes were exposed to simulated ischemia and reoxygenation. Cytosolic pH [2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF)], [Ca.sup.2+] (fura 2), [Na.sup.+] [sodium-binding benzolfuran isophthatlate (SBFI)], and cell length were measured. NHE was inhibited with 3 [Mu]mol/l HOE 642 or 1 [Mu]mol/l 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), and NBS was inhibited with HEPES buffer. During anoxia in bicarbonate buffer, cells developed acidosis and intracellular Na and Ca ([Na.sub.i] and [Ca.sub.i], respectively) overload. During reoxygenation cells underwent hypercontracture (44.0 [+ or -] 4.1% of the preanoxic length). During anoxia in bicarbonate buffer, inhibition of NHE had no effect on changes in intracellular pH ([pH.sub.i]), [Na.sub.i], and [Ca.sub.i], but it significantly reduced the reoxygenation-induced hypercontracture (HOE: 61.0 [+ or -] 1.4%, EIPA: 68.2 [+ or -] 1.8%). The sole inhibition of NBS during anoxia was not protective. We conclude that inhibition of NHE during anoxia protects cardiomyocytes against reoxygenation injury independently of cytosolic acidification and [Ca.sub.i] overload. hypercontracture; pH control; calcium; sodium-hydrogen exchanger

Published
2000

15. Importance of bicarbonate transport for protection of cardiomyocytes against reoxygenation injury

Author

SCHAFER, C., LADILOV, Y. V., SIEGMUND, B., and PIPER, H. M.

Subjects
Ischemia -- Research, Reperfusion (Physiology) -- Research, Muscle cells -- Research, Heart cells -- Research, Bicarbonates -- Physiological aspects, Biological sciences
Abstract

Importance of bicarbonate transport for protection of cardiomyocytes against reoxygenation injury. Am J Physiol Heart Circ Physiol 278: H1457-H1463, 2000.--Isolated cardiomyocytes from adult rats were incubated in anoxic bicarbonate-buffered media at extracellular pH ([pH.sub.o]) 6.4 until a cytosolic [Ca.sup.2+] overload and intracellular pH ([pH.sub.i]) of 6.4 were reached. On reoxygenation, the pH of the medium was changed to 7.4 to activate the [Na.sup.+]/[H.sup.+]exchanger (NHE) and the [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] symporter (NBS). The reoxygenation was performed in the absence or presence of the NHE inhibitor HOE-642 (3 [micro]mol/l) and/or the NBS inhibitor DIDS (0.5 mmol/l), as in bicarbonate-free media. In reoxygenated control cells [ph.sub.i] rapidly recovered to the preanoxic level, and a burst of spontaneous oscillations of cytosolic [Ca.sup.2+] occurred, accompanied by the development of hypercontracture. When NBS and NHE were simultaneously inhibited during reoxygenation, [ph.sub.i] recovery was prevented, [Ca.sup.2+] oscillations were attenuated, and hypercontracture was abolished. Sole inhibition of NBS or NHE showed no protection against hypercontracture. In the absence of cytosolic acidosis, HOE-642 or DIDS did not prevent hypercontracture induced by [Ca.sup.2+] overload. The results demonstrate that simultaneous inhibition of NHE and NBS is needed to protect myocardial cells against reoxygenation-induced hypercontracture. ischemia; reperfusion; myocytes

Published
2000

16. Poster session 2

Author

Perez-Pomares, J. M., primary, Ruiz-Villalba, A., additional, Ziogas, A., additional, Segovia, J. C., additional, Ehrbar, M., additional, Munoz-Chapuli, R., additional, De La Rosa, A., additional, Dominguez, J. N., additional, Hove-Madsen, L., additional, Sankova, B., additional, Sedmera, D., additional, Franco, D., additional, Aranega Jimenez, A., additional, Babaeva, G., additional, Chizh, N., additional, Galchenko, S., additional, Sandomirsky, B., additional, Schwarzl, M., additional, Seiler, S., additional, Steendijk, P., additional, Huber, S., additional, Maechler, H., additional, Truschnig-Wilders, M., additional, Pieske, B., additional, Post, H., additional, Simrick, S., additional, Kreutzer, R., additional, Rao, C., additional, Terracciano, C. M., additional, Kirchhof, P., additional, Fabritz, L., additional, Brand, T., additional, Theveniau-Ruissy, M., additional, Parisot, P., additional, Francou, A., additional, Saint-Michel, E., additional, Mesbah, K., additional, Kelly, R. G., additional, Wu, H.-T., additional, Sie, S.-S., additional, Chen, C.-Y., additional, Kuan, T.-C., additional, Lin, C. S., additional, Ismailoglu, Z., additional, Guven, M., additional, Yakici, A., additional, Ata, Y., additional, Ozcan, S., additional, Yildirim, E., additional, Ongen, Z., additional, Miroshnikova, V., additional, Demina, E., additional, Rodygina, T., additional, Kurjanov, P., additional, Denisenko, A., additional, Schwarzman, A., additional, Rubanenko, A., additional, Shchukin, Y., additional, Germanov, A., additional, Goldbergova, M., additional, Parenica, J., additional, Lipkova, J., additional, Pavek, N., additional, Kala, P., additional, Poloczek, M., additional, Vasku, A., additional, Parenicova, I., additional, Spinar, J., additional, Gambacciani, C., additional, Chiavacci, E., additional, Evangelista, M., additional, Vesentini, N., additional, Kusmic, C., additional, Pitto, L., additional, Chernova, A., additional, Nikulina, S. U. Y., additional, Arvanitis, D. A., additional, Mourouzis, I., additional, Pantos, C., additional, Kranias, E. G., additional, Cokkinos, D. V., additional, Sanoudou, D., additional, Vladimirskaya, T. E., additional, Shved, I. A., additional, Kryvorot, S. G., additional, Schirmer, I. M., additional, Appukuttan, A., additional, Pott, L., additional, Jaquet, K., additional, Ladilov, Y., additional, Archer, C. R., additional, Bootman, M. D., additional, Roderick, H. L., additional, Fusco, A., additional, Sorriento, D., additional, Santulli, G., additional, Trimarco, B., additional, Iaccarino, G., additional, Hagenmueller, M., additional, Riffel, J., additional, Bernhold, E., additional, Katus, H. A., additional, Hardt, S. E., additional, Maqsood, A., additional, Zi, M., additional, Prehar, S., additional, Neyses, L., additional, Ray, S., additional, Oceandy, D., additional, Khatami, N., additional, Wadowski, P., additional, Wagh, V., additional, Hescheler, J., additional, Sachinidis, A., additional, Mohl, W., additional, Chaudhry, B., additional, Burns, D., additional, Henderson, D. J., additional, Bax, N. A. M., additional, Van Marion, M. H., additional, Shah, B., additional, Goumans, M. J., additional, Bouten, C. V. C., additional, Van Der Schaft, D. W. J., additional, Van Oorschot, A. A. M., additional, Maas, S., additional, Braun, J., additional, Van Tuyn, J., additional, De Vries, A. A. F., additional, Gittenberger-De Groot, A. C., additional, Bageghni, S., additional, Drinkhill, M. J., additional, Batten, T. F. C., additional, Ainscough, J. F. X., additional, Onate, B., additional, Vilahur, G., additional, Ferrer-Lorente, R., additional, Ybarra, J., additional, Diez-Caballero, A., additional, Ballesta-Lopez, C., additional, Moscatiello, F., additional, Herrero, J., additional, Badimon, L., additional, Martin-Rendon, E., additional, Clifford, D. M., additional, Fisher, S. A., additional, Brusnkill, S. J., additional, Doree, C., additional, Mathur, A., additional, Clarke, M., additional, Watt, S. M., additional, Hernandez-Vera, R., additional, Kavanagh, D., additional, Yemm, A. I., additional, Frampton, J., additional, Kalia, N., additional, Terajima, Y., additional, Shimizu, T., additional, Tsuruyama, S., additional, Ishii, H., additional, Sekine, H., additional, Hagiwara, N., additional, Okano, T., additional, Vrijsen, K. R., additional, Chamuleau, S. A. J., additional, Sluijter, J. P. G., additional, Doevendans, P. F. M., additional, Madonna, R., additional, Delli Pizzi, S., additional, Di Donato, L., additional, Mariotti, A., additional, Di Carlo, L., additional, D'ugo, E., additional, Teberino, M. A., additional, Merla, A., additional, T, A., additional, De Caterina, R., additional, Kolker, L., additional, Ali, N. N., additional, Maclellan, K., additional, Moore, M., additional, Wheeler, J., additional, Harding, S. E., additional, Fleck, R. A., additional, Rowlinson, J. M., additional, Kraenkel, N., additional, Ascione, R., additional, Madeddu, P., additional, O'sullivan, J. F., additional, Leblond, A. L., additional, Kelly, G., additional, Kumar, A. H. S., additional, Metharom, P., additional, Buneker, C. K., additional, Alizadeh-Vikali, N., additional, Hynes, B. G., additional, O'connor, R., additional, Caplice, N. M., additional, Noseda, M., additional, De Smith, A. J., additional, Leja, T., additional, Rao, P. H., additional, Al-Beidh, F., additional, Abreu Pavia, M. S., additional, Blakemore, A. I., additional, Schneider, M. D., additional, Stathopoulou, K., additional, Cuello, F., additional, Ehler, E., additional, Haworth, R. S., additional, Avkiran, M., additional, Morawietz, H., additional, Eickholt, C., additional, Langbein, H., additional, Brux, M., additional, Goettsch, C., additional, Goettsch, W., additional, Arsov, A., additional, Brunssen, C., additional, Mazilu, L., additional, Parepa, I. R., additional, Suceveanu, A. I., additional, Suceveanu, A. P., additional, De Man, F. S., additional, Guignabert, C., additional, Tu, L., additional, Handoko, M. L., additional, Schalij, I., additional, Fadel, E., additional, Postmus, P. E., additional, Vonk-Noordegraaf, A., additional, Humbert, M., additional, Eddahibi, S., additional, Del Giudice, C., additional, Anastasio, A., additional, Fazal, L., additional, Azibani, F., additional, Bihry, N., additional, Merval, R., additional, Polidano, E., additional, Samuel, J.-L., additional, Delcayre, C., additional, Zhang, Y., additional, Mi, Y. M., additional, Ren, L. L., additional, Cheng, Y. P., additional, Guo, R., additional, Liu, Y., additional, Jiang, Y. N., additional, Kokkinos, A. D., additional, Tretjakovs, P., additional, Jurka, A., additional, Bormane, I., additional, Mikelsone, I., additional, Reihmane, D., additional, Elksne, K., additional, Krievina, G., additional, Verbovenko, J., additional, Bahs, G., additional, Lopez-Andres, N., additional, Rousseau, A., additional, Calvier, L., additional, Akhtar, R., additional, Labat, C., additional, Cruickshank, K., additional, Diez, J., additional, Zannad, F., additional, Lacolley, P., additional, Rossignol, P., additional, Hamesch, K., additional, Subramanian, P., additional, Li, X., additional, Thiemann, A., additional, Heyll, K., additional, Dembowsky, K., additional, Chevalier, E., additional, Weber, C., additional, Schober, A., additional, Yang, L., additional, Kim, G., additional, Gardner, B., additional, Earley, J., additional, Hofmann-Bowman, M., additional, Cheng, C.-F., additional, Lian, W.-S., additional, Lin, H., additional, Jinjolia, N. J., additional, Abuladze, G. A., additional, Tvalchrelidze, S. H. T., additional, Khamnagadaev, I., additional, Shkolnikova, M., additional, Kokov, L., additional, Miklashevich, I., additional, Drozdov, I., additional, Ilyich, I., additional, Bingen, B. O., additional, Askar, S. F. A., additional, Ypey, D. L., additional, Van Der Laarse, A., additional, Schalij, M. J., additional, Pijnappels, D. A., additional, Roney, C. H., additional, Ng, F. S., additional, Chowdhury, R. A., additional, Chang, E. T. Y., additional, Patel, P. M., additional, Lyon, A. R., additional, Siggers, J. H., additional, Peters, N. S., additional, Obergrussberger, A., additional, Stoelzle, S., additional, Bruggemann, A., additional, Haarmann, C., additional, George, M., additional, Fertig, N., additional, Moreira, D., additional, Souza, A., additional, Valente, P., additional, Kornej, J., additional, Reihardt, C., additional, Kosiuk, J., additional, Arya, A., additional, Hindricks, G., additional, Adams, V., additional, Husser, D., additional, Bollmann, A., additional, Camelliti, P., additional, Dudhia, J., additional, Dias, P., additional, Cartledge, J., additional, Connolly, D. J., additional, Nobles, M., additional, Sebastian, S., additional, Tinker, A., additional, Opel, A., additional, Daimi, H., additional, Haj Khelil, A., additional, Be Chibani, J., additional, Barana, A., additional, Amoros, I., additional, Gonzalez De La Fuente, M., additional, Caballero, R., additional, Aranega, A., additional, Kelly, A., additional, Bernus, O., additional, Kemi, O. J., additional, Myles, R. C., additional, Ghouri, I. A., additional, Burton, F. L., additional, Smith, G. L., additional, Del Lungo, M., additional, Sartiani, L., additional, Spinelli, V., additional, Baruscotti, M., additional, Difrancesco, D., additional, Mugelli, A., additional, Cerbai, E., additional, Thomas, A. M., additional, Aziz, Q., additional, Khambra, T., additional, Addlestone, J. M. A., additional, Cartwright, E. J., additional, Wilkinson, R., additional, Song, W., additional, Marston, S., additional, Jacquet, A., additional, Mougenot, N. M., additional, Lipskaia, A. J., additional, Paalberends, E. R., additional, Stam, K., additional, Van Dijk, S. J., additional, Van Slegtenhorst, M., additional, Dos Remedios, C., additional, Ten Cate, F. J., additional, Michels, M., additional, Niessen, H. W. M., additional, Stienen, G. J. M., additional, Van Der Velden, J., additional, Read, M. I., additional, Andreianova, A. A., additional, Harrison, J. C., additional, Goulton, C. S., additional, Kerr, D. S., additional, Sammut, I. A., additional, Wallner, M., additional, Von Lewinski, D., additional, Kindsvater, D., additional, Saes, M., additional, Morano, I., additional, Muegge, A., additional, Buyandelger, B., additional, Kostin, S., additional, Gunkel, S., additional, Vouffo, J., additional, Ng, K., additional, Chen, J., additional, Eilers, M., additional, Isaacson, R., additional, Milting, H., additional, Knoell, R., additional, Cattin, M.-E., additional, Crocini, C., additional, Schlossarek, S., additional, Maron, S., additional, Hansen, A., additional, Eschenhagen, T., additional, Carrier, L., additional, Bonne, G., additional, Coppini, R., additional, Ferrantini, C., additional, Olivotto, I., additional, Belardinelli, L., additional, Poggesi, C., additional, Leung, M. C., additional, Messer, A. E., additional, Copeland, O., additional, Marston, S. B., additional, Mills, A. M., additional, Collins, T., additional, O'gara, P., additional, Thum, T., additional, Regalla, K., additional, Macleod, K. T., additional, Prodromakis, T., additional, Chaudhry, U., additional, Darzi, A., additional, Yacoub, M. H., additional, Athanasiou, T., additional, Bogdanova, A., additional, Makhro, A., additional, Hoydal, M., additional, Stolen, T. O., additional, Johnssen, A. B., additional, Alves, M., additional, Catalucci, D., additional, Condorelli, G., additional, Koch, L. G., additional, Britton, S. L., additional, Wisloff, U., additional, Bito, V., additional, Claus, P., additional, Vermeulen, K., additional, Huysmans, C., additional, Ventura-Clapier, R., additional, Sipido, K. R., additional, Seliuk, M. N., additional, Burlaka, A. P., additional, Sidorik, E. P., additional, Khaitovych, N. V., additional, Kozachok, M. M., additional, Potaskalova, V. S., additional, Driesen, R. B., additional, Galan, D. T., additional, De Paulis, D., additional, Arnoux, T., additional, Schaller, S., additional, Pruss, R. M., additional, Poitz, D. M., additional, Augstein, A., additional, Braun-Dullaeus, R. C., additional, Schmeisser, A., additional, Strasser, R. H., additional, Micova, P., additional, Balkova, P., additional, Hlavackova, M., additional, Zurmanova, J., additional, Kasparova, D., additional, Kolar, F., additional, Neckar, J., additional, Novak, F., additional, Novakova, O., additional, Pollard, S., additional, Babba, M., additional, Hussain, A., additional, James, R., additional, Maddock, H., additional, Alshehri, A. S., additional, Baxter, G. F., additional, Dietel, B., additional, Altendorf, R., additional, Daniel, W. G., additional, Kollmar, R., additional, Garlichs, C. D., additional, Sirohi, R., additional, Roberts, N., additional, Lawrence, D., additional, Sheikh, A., additional, Kolvekar, S., additional, Yap, J., additional, Arend, M., additional, Walkinshaw, G., additional, Hausenloy, D. J., additional, Yellon, D. M., additional, Posa, A., additional, Szabo, R., additional, Szalai, Z., additional, Szablics, P., additional, Berko, M. A., additional, Orban, K., additional, Murlasits, Z. S., additional, Balogh, L., additional, Varga, C., additional, Ku, H. C., additional, Su, M. J., additional, Chreih, R.-M., additional, Ginghina, C., additional, Deleanu, D., additional, Ferreira, A. L. B. J., additional, Belal, A., additional, Ali, M. A., additional, Fan, X., additional, Holt, A., additional, Campbell, R., additional, Schulz, R., additional, Bonanad, C., additional, Bodi, V., additional, Sanchis, J., additional, Morales, J. M., additional, Marrachelli, V., additional, Nunez, J., additional, Forteza, M. J., additional, Chaustre, F., additional, Gomez, C., additional, Chorro, F. J., additional, Csont, T., additional, Fekete, V., additional, Murlasits, Z., additional, Aypar, E., additional, Bencsik, P., additional, Sarkozy, M., additional, Varga, Z. V., additional, Ferdinandy, P., additional, Duerr, G. D., additional, Zoerlein, M., additional, Dewald, D., additional, Mesenholl, B., additional, Schneider, P., additional, Ghanem, A., additional, Rittling, S., additional, Welz, A., additional, Dewald, O., additional, Becker, E., additional, Peigney, C., additional, Bouleti, C., additional, Galaup, A., additional, Monnot, C., additional, Ghaleh, B., additional, Germain, S., additional, Timmermans, A., additional, Ginion, A., additional, De Meester, C., additional, Sakamoto, K., additional, Vanoverschelde, J.-L., additional, Horman, S., additional, Beauloye, C., additional, Bertrand, L., additional, Maroz-Vadalazhskaya, N., additional, Drozd, E., additional, Kukharenko, L., additional, Russkich, I., additional, Krachak, D., additional, Seljun, Y., additional, Ostrovski, Y., additional, Martin, A.-C., additional, Le Bonniec, B., additional, Lecompte, T., additional, Dizier, B., additional, Emmerich, J., additional, Fischer, A.-M., additional, Samama, C.-M., additional, Godier, A., additional, Mogensen, S., additional, Furchtbauer, E. M., additional, Aalkjaer, C., additional, Choong, W. L., additional, Jovanovic, A., additional, Khan, F., additional, Daniel, J. M., additional, Dutzmann, J. M., additional, Widmer-Teske, R., additional, Guenduez, D., additional, Sedding, D., additional, Castro, M. M., additional, Cena, J. J. C., additional, Cho, W. J. C., additional, Goobie, G. G., additional, Walsh, M. P. W., additional, Schulz, R. S., additional, Dutzmann, J., additional, Preissner, K. T., additional, Sones, W., additional, Kotlikoff, M., additional, Serizawa, K., additional, Yogo, K., additional, Aizawa, K., additional, Hirata, M., additional, Tashiro, Y., additional, Ishizuka, N., additional, Varela, A., additional, Katsiboulas, M., additional, Tousoulis, D., additional, Papaioannou, T. G., additional, Vaina, S., additional, Davos, C. H., additional, Piperi, C., additional, Stefanadis, C., additional, Basdra, E. K., additional, Papavassiliou, A. G., additional, Hermenegildo, C., additional, Lazaro-Franco, M., additional, Sobrino, A., additional, Bueno-Beti, C., additional, Martinez-Gil, N., additional, Walther, T., additional, Peiro, C., additional, Sanchez-Ferrer, C. F., additional, Novella, S., additional, Ciccarelli, M., additional, Franco, A., additional, Dorn, G. W., additional, Cseplo, P., additional, Torok, O., additional, Springo, Z. S., additional, Vamos, Z., additional, Kosa, D., additional, Hamar, J., additional, Koller, A., additional, Bubb, K. J., additional, Ahluwalia, A., additional, Stepien, E. L., additional, Gruca, A., additional, Grzybowska, J., additional, Goralska, J., additional, Dembinska-Kiec, A., additional, Stolinski, J., additional, Partyka, L., additional, Zhang, H., additional, Sweeney, D., additional, Thomas, G. N., additional, Fish, P. V., additional, Taggart, D. P., additional, Cioffi, S., additional, Bilio, M., additional, Martucciello, S., additional, Illingworth, E., additional, Caporali, A., additional, Shantikumar, S., additional, Marchetti, M., additional, Martelli, F., additional, Emanueli, C., additional, Meloni, M., additional, Al Haj Zen, A., additional, Sala-Newby, G., additional, Del Turco, S., additional, Saponaro, C., additional, Dario, B., additional, Sartini, S., additional, Menciassi, A., additional, Dario, P., additional, La Motta, C., additional, Basta, G., additional, Santiemma, V., additional, Bertone, C., additional, Rossi, F., additional, Michelon, E., additional, Bianco, M. J., additional, Castelli, A., additional, Shin, D. I., additional, Seung, K. B., additional, Seo, S. M., additional, Park, H. J., additional, Kim, P. J., additional, Baek, S. H., additional, Choi, Y. S., additional, Her, S. H., additional, Kim, D. B., additional, Lee, J. M., additional, Park, C. 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J., additional, Mangold, A., additional, Puthenkalam, S., additional, Distelmaier, K., additional, Adlbrecht, C., additional, Lang, I. M., additional, Koizumi, T., additional, Inoue, I., additional, Komiyama, N., additional, Nishimura, S., additional, Korneeva, O. N., additional, Drapkina, O. M., additional, Fornai, L., additional, Angelini, A., additional, Kiss, A., additional, Giskes, F., additional, Eijkel, G., additional, Fedrigo, M., additional, Valente, M. L., additional, Thiene, G., additional, Heeren, R. M. A., additional, Padro, T., additional, Casani, L., additional, Suades, R., additional, Bertoni, B., additional, Carminati, R., additional, Carlini, V., additional, Pettinari, L., additional, Martinelli, C., additional, Gagliano, N., additional, Noppe, G., additional, Buchlin, P., additional, Marquet, N., additional, Baeyens, N., additional, Morel, N., additional, Baysa, A., additional, Sagave, J., additional, Dahl, C. P., additional, Gullestad, L., additional, Carpi, A., additional, Di Lisa, F., additional, Giorgio, M., additional, Vaage, J., additional, Valen, G., additional, Vafiadaki, E., additional, Papalouka, V., additional, Terzis, G., additional, Spengos, K., additional, Manta, P., additional, Gales, C., additional, Genet, G., additional, Dague, E., additional, Cazorla, O., additional, Payre, B., additional, Mias, C., additional, Ouille, A., additional, Lacampagne, A., additional, Pathak, A., additional, Senard, J. M., additional, Abonnenc, M., additional, Da Costa Martins, P., additional, Srivastava, S., additional, Gautel, M., additional, De Windt, L., additional, Comelli, L., additional, Lande, C., additional, Ucciferri, N., additional, Ikonen, L., additional, Vuorenpaa, H., additional, Kujala, K., additional, Sarkanen, J.-R., additional, Heinonen, T., additional, Ylikomi, T., additional, Aalto-Setala, K., additional, Capros, H., additional, Sprincean, N., additional, Usurelu, N., additional, Egorov, V., additional, Stratu, N., additional, Matchkov, V., additional, Bouzinova, E., additional, Moeller-Nielsen, N., additional, Wiborg, O., additional, Gutierrez, P. S., additional, Aparecida-Silva, R., additional, Borges, L. F., additional, Moreira, L. F. P., additional, Dias, R. R., additional, Kalil, J., additional, Stolf, N. A. G., additional, Zhou, W., additional, Suntharalingam, K., additional, Brand, N., additional, Vilar Compte, R., additional, Ying, L., additional, Bicknell, K., additional, Dannoura, A., additional, Dash, P., additional, Brooks, G., additional, Tsimafeyeu, I., additional, Tishova, Y., additional, Wynn, N., additional, Oyeyipo, I. P., additional, Olatunji, L. A., additional, Maegdefessel, L., additional, Azuma, J., additional, Toh, R., additional, Raaz, U., additional, Merk, D. R., additional, Deng, A., additional, Spin, J. M., additional, Tsao, P. S., additional, Tedeschi, L., additional, Taranta, M., additional, Naldi, I., additional, Grimaldi, S., additional, Cinti, C., additional, Bousquenaud, M., additional, Maskali, F., additional, Poussier, S., additional, Marie, P. Y., additional, Boutley, H., additional, Karcher, G., additional, Wagner, D. 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F., additional, Villar, A. V., additional, Perez-Moreno, A., additional, Gilabert, R., additional, and Ros, E., additional

Published
2012
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36. Role of the reverse mode of the Na+/Ca2+ exchanger in reoxygenation-induced cardiomyocyte injury.

Author

Schäfer, C, Ladilov, Y, Inserte, J, Schäfer, M, Haffner, S, Garcia-Dorado, D, and Piper, H.M

Abstract

Objective: We have recently shown that spontaneous Ca2+ oscillations elicit irreversible hypercontracture of cardiomyocytes during reoxygenation. The aim of this study was to investigate whether influx of exterior Ca2+ through the reverse mode of the Na+/Ca2+ exchanger (NCE) contributes to the development of these oscillations and, therefore, to reoxygenation-induced hypercontracture. Methods: Isolated cardiomyocytes and hearts from rats were used as models. Cardiomyocytes were exposed to 60 min simulated ischemia (pHo 6.4) and 10 min reoxygenation (pHo 7.4). During reoxygenation cardiomyocytes were superfused with medium containing 1 mmol/l Ca2+ (control), with nominally Ca2+-free medium or with medium containing 10 μmol/l KB-R 7943 (KB), a selective inhibitor of the reverse mode of the NCE. Results: In reoxygenated cardiomyocytes rapid Ca2+ oscillations occurred which were reduced under Ca2+-free conditions or in presence of KB. Hypercontracture was also significantly reduced under Ca2+-free conditions or in presence of KB. After 30 min of normoxic perfusion isolated rat hearts were subjected to 60 min global ischemia and reperfusion. KB (10 μmol/l) was present during the first 10 min of reperfusion. LVEDP, LVdevP and lactate dehydrogenase (LDH) release were measured. Presence of KB reduced post-ischemic LVEDP and improved left ventricular function (LVdevP). In KB treated hearts the reperfusion induced release of LDH was markedly reduced from 81.1±9.9 (control) to 49.3±8.8 U/60 min/g dry weight. Conclusion: Our study shows that inhibition of the reverse mode of the NCE, during reperfusion only, protects cardiomyocytes and whole hearts against reperfusion injury. [ABSTRACT FROM PUBLISHER]

Published
2001

38. The role of Na+/H+ exchange in ischemia-reperfusion

Author

Piper, H. M., Balser, C., Ladilov, Y. V., Schäfer, M., Siegmund, B., Ruiz-Meana, M., and Garcia-Dorado, D.

Abstract

In ischemia the cytosol of cardiomyocytes acidifies; this is reversed upon reperfusion. One of the major pHi-regulating transport systems involved is the Na+/H+ exchanger. Inhibitors of the Na+/H+ exchanger have been found to more effectively protect ischemic-reperfused myocardium when administered before and during ischemia than during reperfusion alone. It has been hypothesized that the protection provided by pre-ischemic administration is due to a reduction in Na+ and secondary Ca2+ influx. Under reperfusion conditions Na+/H+ exchange inhibition also seems protective since it prolongs intracellular acidosis which can prevent hypercontracture. In detail, however, the mechanisms by which Na+/H+ exchange inhibition provides protection in ischemic-reperfused myocardium are still not fully identified.

Published
1996
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40. Modulation of early [Ca[sup 2+]][sub i] rise in metabolically inhibited endothelial cells by...

Author

Schafer, M., Bahde, D., Bosche, B., Ladilov, Y., Schafer, C., Piper, H.M., and Noll, T.

Subjects
*CALCIUM metabolism, *BIOENERGETICS, *GLYCOLYSIS
Abstract

Analyzes the importance of adenosine triphosphate production through glycolysis and the mechanism of calcium loss from the endoplasmic reticulum (ER). Indication that the ER of endothelial cells is very sensitive to glycolytic metabolic inhibition; Discharging of the ER calcium store by opening of the D-myo-inositol 3-phosphate-sensitive release channel.

Published
2001

41. Role of AMPK and Sirtuins in Aging Heart: Basic and Translational Aspects.

Author

Barcena ML, Aslam M, Norman K, Ott C, and Ladilov Y

Abstract

Aging is a key risk factor for numerous diseases, including cardiac diseases. High energy demands of the heart require precise cellular energy sensing to prevent metabolic stress. AMPK and sirtuins are key intracellular metabolic sensors regulating numerous cell functions, like mitochondrial function and biogenesis, autophagy, and redox balance. However, their function is impaired during the aging process leading to mitochondrial dysfunction, oxidative stress, and inflammation culminating in cardiovascular diseases. The underlying molecular mechanisms leading to dysfunction of metabolic sensing in the aging heart are complex and comprise both intracellular and systemic age-related alterations. In this study, we overview the current knowledge on the impact of aging on cardiac metabolic sensing, with a focus on AMPK and sirtuins, while mTOR pathway was only marginally considered. A particular focus was given to systemic factors, e.g., inflammation, vascular diseases, and microbiome.

Published
2024
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42. Sex Differences in Expression of Pro-Inflammatory Markers and miRNAs in a Mouse Model of CVB3 Myocarditis.

Author

Estepa M, Niehues MH, Vakhrusheva O, Haritonow N, Ladilov Y, Barcena ML, and Regitz-Zagrosek V

Subjects
Animals, Female, Male, Mice, Enterovirus B, Human, Biomarkers metabolism, Sex Characteristics, Cytokines metabolism, Cytokines genetics, Myocardium metabolism, Myocardium pathology, Inflammation genetics, Inflammation metabolism, Sex Factors, Gene Expression Regulation, Myocarditis metabolism, Myocarditis virology, Myocarditis genetics, MicroRNAs genetics, MicroRNAs metabolism, Disease Models, Animal, Coxsackievirus Infections metabolism, Coxsackievirus Infections genetics, Coxsackievirus Infections virology
Abstract

Myocarditis is an inflammatory disease that may lead to dilated cardiomyopathy. Viral infection of the myocardium triggers immune responses, which involve, among others, macrophage infiltration, oxidative stress, expression of pro-inflammatory cytokines, and microRNAs (miRNAs). The cardioprotective role of estrogen in myocarditis is well documented; however, sex differences in the miRNA expression in chronic myocarditis are still poorly understood, and studying them further was the aim of the present study. Male and female ABY/SnJ mice were infected with CVB3. Twenty-eight days later, cardiac tissue from both infected and control mice was used for real-time PCR and Western blot analysis. NFκB, IL-6, iNOS, TNF-α, IL-1β, MCP-1, c-fos, and osteopontin (OPN) were used to examine the inflammatory state in the heart. Furthermore, the expression of several inflammation- and remodeling-related miRNAs was analyzed. NFκB, IL-6, TNF-α, IL-1β, iNOS, and MCP-1 were significantly upregulated in male mice with CVB3-induced chronic myocarditis, whereas OPN mRNA expression was increased only in females. Further analysis revealed downregulation of some anti-inflammatory miRNA in male hearts (let7a), with upregulation in female hearts (let7b). In addition, dysregulation of remodeling-related miRNAs (miR27b and mir199a) in a sex-dependent manner was observed. Taken together, the results of the present study suggest a sex-specific expression of pro-inflammatory markers as well as inflammation- and remodeling-related miRNAs, with a higher pro-inflammatory response in male CVB3 myocarditis mice.

Published
2024
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43. Upregulation of Mitochondrial Sirt3 and Alleviation of the Inflammatory Phenotype in Macrophages by Estrogen.

Author

Barcena ML, Christiansen-Mensch C, Aslam M, Haritonow N, Ladilov Y, and Regitz-Zagrosek V

Subjects
Animals, Female, Male, Mice, Acetylation drug effects, Estradiol pharmacology, Mice, Inbred C57BL, Phenotype, RAW 264.7 Cells, Estrogens pharmacology, Inflammation pathology, Inflammation metabolism, Macrophages metabolism, Macrophages drug effects, Mitochondria metabolism, Mitochondria drug effects, Sirtuin 3 metabolism, Up-Regulation drug effects
Abstract

Background: Aging and comorbidities like type 2 diabetes and obesity contribute to the development of chronic systemic inflammation, which impacts the development of heart failure and vascular disease. Increasing evidence suggests a role of pro-inflammatory M1 macrophages in chronic inflammation. A shift of metabolism from mitochondrial oxidation to glycolysis is essential for the activation of the pro-inflammatory M1 phenotype. Thus, reprogramming the macrophage metabolism may alleviate the pro-inflammatory phenotype and protect against cardiovascular diseases. In the present study, we hypothesized that the activation of estrogen receptors leads to the elevation of the mitochondrial deacetylase Sirt3, which supports mitochondrial function and mitigates the pro-inflammatory phenotype in macrophages., Materials and Methods: Experiments were performed using the mouse macrophage cell line RAW264.7, as well as primary male or female murine bone marrow macrophages (BMMs). Macrophages were treated for 24 h with estradiol (E2) or vehicle (dextrin). The effect of E2 on Sirt3 expression was investigated in pro-inflammatory M1, anti-inflammatory/immunoregulatory M2, and naïve M0 macrophages. Mitochondrial respiration was measured by Seahorse assay, and protein expression and acetylation were determined by western blotting., Results: E2 treatment upregulated mitochondrial Sirt3, reduced mitochondrial protein acetylation, and increased basal mitochondrial respiration in naïve RAW264.7 macrophages. Similar effects on Sirt3 expression and mitochondrial protein acetylation were observed in primary female but not in male murine BMMs. Although E2 upregulated Sirt3 in naïve M0, pro-inflammatory M1, and anti-inflammatory/immunoregulatory M2 macrophages, it reduced superoxide dismutase 2 acetylation and suppressed mitochondrial reactive oxygen species formation only in pro-inflammatory M1 macrophages. E2 alleviated the pro-inflammatory phenotype in M1 RAW264.7 cells., Conclusions: The study suggests that E2 treatment upregulates Sirt3 expression in macrophages. In primary BMMs, female-specific Sirt3 upregulation was observed. The Sirt3 upregulation was accompanied by mitochondrial protein deacetylation and the alleviation of the oxidative and pro-inflammatory phenotype in M1 macrophages. Thus, the E2-Sirt3 axis might be used in a therapeutic strategy to fight chronic systemic inflammation and prevent the development of inflammation-linked diseases.

Published
2024
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46. Sex and age differences in AMPK phosphorylation, mitochondrial homeostasis, and inflammation in hearts from inflammatory cardiomyopathy patients.

Author

Barcena ML, Tonini G, Haritonow N, Breiter P, Milting H, Baczko I, Müller-Werdan U, Ladilov Y, and Regitz-Zagrosek V

Subjects
Humans, Female, Male, Aged, Sirtuin 1 metabolism, AMP-Activated Protein Kinases genetics, AMP-Activated Protein Kinases metabolism, Phosphorylation, NF-kappa B metabolism, Toll-Like Receptor 4 genetics, Toll-Like Receptor 4 metabolism, Inflammation genetics, Inflammation complications, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha metabolism, Myocarditis complications, Cardiomyopathy, Dilated complications, Sirtuin 3 metabolism
Abstract

Linked to exacerbated inflammation, myocarditis is a cardiovascular disease, which may lead to dilated cardiomyopathy. Although sex and age differences in the development of chronic myocarditis have been postulated, underlying cellular mechanisms remain poorly understood. In the current study, we aimed to investigate sex and age differences in mitochondrial homeostasis, inflammation, and cellular senescence. Cardiac tissue samples from younger and older patients with inflammatory dilated cardiomyopathy (DCMI) were used. The expression of Sirt1, phosphorylated AMPK, PGC-1α, Sirt3, acetylated SOD2, catalase, and several mitochondrial genes was analyzed to assess mitochondrial homeostasis. The expression of NF-κB, TLR4, and interleukins was used to examine the inflammatory state in the heart. Finally, several senescence markers and telomere length were investigated. Cardiac AMPK expression and phosphorylation were significantly elevated in male DCMI patients, whereas Sirt1 expression remained unchanged in all groups investigated. AMPK upregulation was accompanied by a preserved expression of all mitochondrial proteins/genes investigated in older male DCMI patients, whereas the expression of TOM40, TIM23, and the mitochondrial oxidative phosphorylation genes was significantly reduced in older female patients. Mitochondrial homeostasis in older male patients was further supported by the reduced acetylation of mitochondrial proteins as indicated by acetylated SOD2. The inflammatory markers NF-κB and TLR4 were downregulated in older male DCMI patients, whereas the expression of IL-18 was increased in older female patients. This was accompanied by progressed senescence in older DCMI hearts. In conclusion, older women experience more dramatic immunometabolic disorders on the cellular level than older men., (© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Published
2023
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47. New Insights into the Basic and Translational Aspects of AMPK Signaling.

Author

Ladilov Y and Aslam M

Subjects
Signal Transduction physiology, AMP-Activated Protein Kinases metabolism, Protein Processing, Post-Translational
Abstract

5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) is an enzyme regulating numerous cellular processes involved in cell survival as well as health- and lifespan [...].

Published
2023
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48. Claudin-10a Deficiency Shifts Proximal Tubular Cl - Permeability to Cation Selectivity via Claudin-2 Redistribution.

Author

Breiderhoff T, Himmerkus N, Meoli L, Fromm A, Sewerin S, Kriuchkova N, Nagel O, Ladilov Y, Krug SM, Quintanova C, Stumpp M, Garbe-Schönberg D, Westernströer U, Merkel C, Brinkhus MA, Altmüller J, Schweiger MR, Müller D, Mutig K, Morawski M, Halbritter J, Milatz S, Bleich M, and Günzel D

Subjects
Animals, Cations metabolism, Kidney Tubules, Proximal metabolism, Mice, Permeability, Tight Junctions physiology, Claudin-2, Claudins metabolism
Abstract

Background: The tight junction proteins claudin-2 and claudin-10a form paracellular cation and anion channels, respectively, and are expressed in the proximal tubule. However, the physiologic role of claudin-10a in the kidney has been unclear., Methods: To investigate the physiologic role of claudin-10a, we generated claudin-10a-deficient mice, confirmed successful knockout by Southern blot, Western blot, and immunofluorescence staining, and analyzed urine and serum of knockout and wild-type animals. We also used electrophysiologic studies to investigate the functionality of isolated proximal tubules, and studied compensatory regulation by pharmacologic intervention, RNA sequencing analysis, Western blot, immunofluorescence staining, and respirometry., Results: Mice deficient in claudin-10a were fertile and without overt phenotypes. On knockout, claudin-10a was replaced by claudin-2 in all proximal tubule segments. Electrophysiology showed conversion from paracellular anion preference to cation preference and a loss of paracellular Cl - over HCO 3 - preference. As a result, there was tubular retention of calcium and magnesium, higher urine pH, and mild hypermagnesemia. A comparison with other urine and serum parameters under control conditions and sequential pharmacologic transport inhibition, and unchanged fractional lithium excretion, suggested compensative measures in proximal and distal tubular segments. Changes in proximal tubular oxygen handling and differential expression of genes regulating fatty acid metabolism indicated proximal tubular adaptation. Western blot and immunofluorescence revealed alterations in distal tubular transport., Conclusions: Claudin-10a is the major paracellular anion channel in the proximal tubule and its deletion causes calcium and magnesium hyper-reabsorption by claudin-2 redistribution. Transcellular transport in proximal and distal segments and proximal tubular metabolic adaptation compensate for loss of paracellular anion permeability., (Copyright © 2022 by the American Society of Nephrology.)

Published
2022
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49. Cardiovascular Inflammaging: Mechanisms and Translational Aspects.

Author

Barcena ML, Aslam M, Pozdniakova S, Norman K, and Ladilov Y

Subjects
Humans, Inflammation etiology, Lung, Cellular Senescence, Diabetes Mellitus, Type 2 complications
Abstract

Aging is one of the major non-reversible risk factors for several chronic diseases, including cancer, type 2 diabetes, dementia, and cardiovascular diseases (CVD), and it is a key cause of multimorbidity, disability, and frailty (decreased physical activity, fatigue, and weight loss). The underlying cellular mechanisms are complex and consist of multifactorial processes, such as telomere shortening, chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, accumulation of senescent cells, and reduced autophagy. In this review, we focused on the molecular mechanisms and translational aspects of cardiovascular aging-related inflammation, i.e., inflammaging.

Published
2022
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50. Emerging Role of cAMP/AMPK Signaling.

Author

Aslam M and Ladilov Y

Subjects
Animals, Humans, Lipid Metabolism, Models, Biological, Protein Biosynthesis, AMP-Activated Protein Kinases metabolism, Cyclic AMP metabolism, Signal Transduction
Abstract

The 5'-Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a natural energy sensor in mammalian cells that plays a key role in cellular and systemic energy homeostasis. At the cellular level, AMPK supports numerous processes required for energy and redox homeostasis, including mitochondrial biogenesis, autophagy, and glucose and lipid metabolism. Thus, understanding the pathways regulating AMPK activity is crucial for developing strategies to treat metabolic disorders. Mounting evidence suggests the presence of a link between cyclic AMP (cAMP) and AMPK signaling. cAMP signaling is known to be activated in circumstances of physiological and metabolic stress due to the release of stress hormones, such as adrenaline and glucagon, which is followed by activation of membrane-bound adenylyl cyclase and elevation of cellular cAMP. Because the majority of physiological stresses are associated with elevated energy consumption, it is not surprising that activation of cAMP signaling may promote AMPK activity. Aside from the physiological role of the cAMP/AMPK axis, numerous reports have suggested its role in several pathologies, including inflammation, ischemia, diabetes, obesity, and aging. Furthermore, novel reports have provided more mechanistic insight into the regulation of the cAMP/AMPK axis. In particular, the role of distinct cAMP microdomains generated by soluble adenylyl cyclase in regulating basal and induced AMPK activity has recently been demonstrated. In the present review, we discuss current advances in the understanding of the regulation of the cAMP/AMPK axis and its role in cellular homeostasis and explore some translational aspects.

Published
2022
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