TY - JOUR AU - Nógrádi-Halmi, Dóra AU - Erdélyi-Furka, Barbara Fanni AU - Molnár-Gáspár, Renáta AU - Csont, Tamás Bálint TI - Triptofán-származékok, mint lehetséges biomarkerek és terápiás célpontok egyes kardiovaszkuláris megbetegedésekben [Tryptophan metabolites as potential biomarkers and therapeutic targets in certain cardiovascular diseases] JF - CARDIOLOGIA HUNGARICA J2 - CARDIOL HUNG VL - 53 PY - 2023 IS - 5 SP - 468 EP - 475 PG - 8 SN - 0133-5596 DO - 10.26430/CHUNGARICA.2023.53.5.468 UR - https://m2.mtmt.hu/api/publication/34416566 ID - 34416566 AB - A gyulladásos folyamatok kiemelkedő szereppel bírnak a vezető halálokok közé sorolható koszorúér-betegségek patomechanizmusában és progressziójában. Ismert, hogy az ezen folyamatok során felszabaduló proinflammatorikus molekulák képesek elősegíteni a triptofán-aminosav kinurenin-útvonalon történő lebomlását. Ez számos immunmodulátor kinurenin-metabolit felszabadulását teszi lehetővé, amelyek között egyaránt szerepelnek jótékony, valamint káros hatással bíró vegyületek. Mai tudásunk szerint a különböző kinurenin-származékok előállításáért felelős metabolikus útvonalak egyensúlyának felborulása fontos szereppel bírhat bizonyos betegségek, köztük egyes kardiovaszkuláris megbetegedések kórlefolyásában. Több tanulmány is alátámasztja, hogy számos kinurenin-metabolit koncentrációjának változása kimutatható koszorúér-betegségben szenvedő páciensektől nyert vér- és/vagy vizeletmintákban. Egyes közlemények szerint bizonyos kinureninek szérumszintje korrelálhat a koronáriabetegségek progressziójával. Összefoglaló tanulmányunk célja annak áttekintése, hogy a kinureninek szereppel bírhatnak-e a jövőben egyes kardiovaszkuláris betegségek rizikóbecslésében, mint biomarkerek, illetve segíthetik-e új terápiás stratégiák kidolgozását. LA - Hungarian DB - MTMT ER - TY - JOUR AU - Pipicz, Márton AU - Demján, Virág AU - Csonka, Csaba AU - Csont, Tamás Bálint TI - Piroptózis, PANoptózis és ferroptózis a szív iszkémia/reperfúziós károsodásában JF - CARDIOLOGIA HUNGARICA J2 - CARDIOL HUNG VL - 53 PY - 2023 IS - 5 SP - 451 EP - 458 PG - 8 SN - 0133-5596 DO - 10.26430/CHUNGARICA.2023.53.5.451 UR - https://m2.mtmt.hu/api/publication/34416562 ID - 34416562 AB - Az intenzív kutatások ellenére továbbra sem rendelkezünk olyan kardioprotektív gyógyszerekkel, amelyek a szív iszkémia/reperfúziós (I/R) károsodásával járó infarktusméretet hatásosan csökkentenék. Ennek egyik magyarázata, hogy az I/R-t kísérő sejtelhalás összetett folyamata teljesen még nem tisztázott. A mechanizmus részletesebb megismerése javíthatja a kardioprotektív gyógyszerfejlesztések transzlálhatóságát. A klasszikus szabályozott (apoptózis, autofágia-mediálta sejthalál) és nem szabályozott (nekrózis) sejthalálfolyamatok mellett olyan programozott sejthalálformákat és mechanizmusokat ismertünk meg az elmúlt években, mint például a piroptózis, a PANoptózis vagy a ferroptózis. Jelen összefoglaló közleményünkben ezen folyamatokat kívánjuk röviden bemutatni a szív I/R károsodásában, valamint kitérünk a lehetséges modulálási stratégiákra is. LA - Hungarian DB - MTMT ER - TY - JOUR AU - Szűcs, Gergő AU - Pipicz, Márton AU - Szabó, Márton Richárd AU - Csont, Tamás Bálint AU - Török, László AU - Csonka, Csaba TI - Effect of Eccentric Exercise on Metabolic Health in Diabetes and Obesity JF - SPORTS MEDICINE-OPEN J2 - SPORT MED-OPEN VL - 9 PY - 2023 IS - 1 PG - 17 SN - 2199-1170 DO - 10.1186/s40798-023-00596-2 UR - https://m2.mtmt.hu/api/publication/34167864 ID - 34167864 AB - There is a growing body of evidence showing the importance of physical activity against civilization-induced metabolic diseases, including type 2 diabetes (T2DM) and obesity. Eccentric contraction, when skeletal muscles generate force by lengthening, is a unique type of skeletal muscle activity. Eccentric contraction may lead to better power production characteristics of the muscle because eccentric contraction requires less energy and can result in higher tension. Therefore, it is an ideal tool in the rehabilitation program of patients. However, the complex metabolic effect (i.e., fat mass reduction, increased lipid oxidation, improvement in blood lipid profile, and increased insulin sensitivity) of the eccentric contraction alone has scarcely been investigated. This paper aims to review the current literature to provide information on whether eccentric contraction can influence metabolic health and body composition in T2DM or obesity. We also discussed the potential role of myokines in mediating the effects of eccentric exercise. A better understanding of the mechanism of eccentric training and particularly their participation in the regulation of metabolic diseases may widen their possible therapeutic use and, thereby, may support the fight against the leading global risks for mortality in the world. LA - English DB - MTMT ER - TY - JOUR AU - Szabó, Márton Richárd AU - Csont, Tamás Bálint AU - Csonka, Csaba TI - The effect of electrical stimulation of skeletal muscle on cardioprotection and on muscle-derived myokine levels in rats: A pilot study JF - PHYSIOLOGY INTERNATIONAL J2 - PHYSIOL INT VL - 110 PY - 2023 IS - 2 SP - 135 EP - 149 PG - 15 SN - 2498-602X DO - 10.1556/2060.2023.00198 UR - https://m2.mtmt.hu/api/publication/34008336 ID - 34008336 N1 - Department of Biochemistry, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, H-6720, Hungary Centre of Excellence for Interdisciplinary Research, Development and Innovation of the University of Szeged, Szeged, H-6720, Hungary Export Date: 7 September 2023 Correspondence Address: Csonka, C.; Department of Biochemistry, Hungary D m t r 9, Hungary; email: csonka.csaba@med.u-szeged.hu AB - Electrical muscle stimulation (EMS) is a widely used method in sports and rehabilitation therapies to simulate physical exercise. EMS treatment via skeletal muscle activity improves the cardiovascular functions and the overall physical condition of the patients. However, the cardioprotective effect of EMS has not been proven so far, therefore, the aim of this study was to investigate the potential cardiac conditioning effect of EMS in an animal model. Low-frequency 35-min EMS was applied to the gastrocnemius muscle of male Wistar rats for three consecutive days. Their isolated hearts were then subjected to 30 min global ischemia and 120 min reperfusion. At the end of reperfusion cardiac specific creatine kinase (CK-MB) and lactate dehydrogenase (LDH) enzyme release and myocardial infarct size were determined. Additionally, skeletal muscle-driven myokine expression and release were also assessed. Phosphorylation of cardioprotective signaling pathway members AKT, ERK1/2, and STAT3 proteins were also measured. EMS significantly attenuated cardiac LDH and CK-MB enzyme activities in the coronary effluents at the end of the ex vivo reperfusion. EMS treatment considerably altered the myokine content of the stimulated gastrocnemius muscle without altering circulating myokine levels in the serum. Additionally, phosphorylation of cardiac AKT, ERK1/2, and STAT3 was not significantly different in the two groups. Despite the lack of significant infarct size reduction, the EMS treatment seems to influence the course of cellular damage due to ischemia/reperfusion and favorably modifies skeletal muscle myokine expressions. Our results suggest that EMS may have a protective effect on the myocardium, however, further optimization is required. LA - English DB - MTMT ER - TY - JOUR AU - Sárközy, Márta AU - Watzinger, Simon AU - Kovács, Zsuzsanna AU - Acar, Eylem AU - Márványkövi, Fanni AU - Szűcs, Gergő AU - Lauber, Gülsüm Yilmaz AU - Galla, Zsolt AU - Siska, Andrea AU - Földesi, Imre AU - Fintha, Attila AU - Kriston, András AU - Kovács, Ferenc AU - Horváth, Péter AU - Kővári, Bence AU - Cserni, Gábor AU - Krenács, Tibor AU - Szabó, Petra Lujza AU - Szabó, Gábor Tamás AU - Monostori, Péter AU - Zins, Karin AU - Abraham, Dietmar AU - Csont, Tamás Bálint AU - Pokreisz, Peter AU - Podesser, Bruno K. AU - Kiss, Attila TI - Neuregulin-1β Improves Uremic Cardiomyopathy and Renal Dysfunction in Rats JF - JACC:BASIC TO TRANSLATIONAL SCIENCE J2 - JACC-BASIC TRANSL SC VL - 8 PY - 2023 IS - 9 SP - 1160 EP - 1176 PG - 17 SN - 2452-302X DO - 10.1016/j.jacbts.2023.03.003 UR - https://m2.mtmt.hu/api/publication/33941648 ID - 33941648 LA - English DB - MTMT ER - TY - JOUR AU - Faragó, Anikó AU - Zsindely, Nóra AU - Farkas, Anita AU - Neller, Alexandra AU - Siági, Fruzsina AU - Szabó, Márton Richárd AU - Csont, Tamás Bálint AU - Bodai, László TI - Acetylation State of Lysine 14 of Histone H3.3 Affects Mutant Huntingtin Induced Pathogenesis JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 23 PG - 23 SN - 1661-6596 DO - 10.3390/ijms232315173 UR - https://m2.mtmt.hu/api/publication/33322061 ID - 33322061 N1 - Export Date: 3 May 2023 AB - Huntington’s Disease (HD) is a fatal neurodegenerative disorder caused by the expansion of a polyglutamine-coding CAG repeat in the Huntingtin gene. One of the main causes of neurodegeneration in HD is transcriptional dysregulation that, in part, is caused by the inhibition of histone acetyltransferase (HAT) enzymes. HD pathology can be alleviated by increasing the activity of specific HATs or by inhibiting histone deacetylase (HDAC) enzymes. To determine which histone’s post-translational modifications (PTMs) might play crucial roles in HD pathology, we investigated the phenotype-modifying effects of PTM mimetic mutations of variant histone H3.3 in a Drosophila model of HD. Specifically, we studied the mutations (K→Q: acetylated; K→R: non-modified; and K→M: methylated) of lysine residues K9, K14, and K27 of transgenic H3.3. In the case of H3.3K14Q modification, we observed the amelioration of all tested phenotypes (viability, longevity, neurodegeneration, motor activity, and circadian rhythm defects), while H3.3K14R had the opposite effect. H3.3K14Q expression prevented the negative effects of reduced Gcn5 (a HAT acting on H3K14) on HD pathology, while it only partially hindered the positive effects of heterozygous Sirt1 (an HDAC acting on H3K14). Thus, we conclude that the Gcn5-dependent acetylation of H3.3K14 might be an important epigenetic contributor to HD pathology. LA - English DB - MTMT ER - TY - CHAP AU - Nógrádi-Halmi, Dóra AU - Molnár-Gáspár, Renáta AU - Csontné Kiricsi, Mónika AU - Nóra, Igaz AU - Csont, Tamás Bálint ED - Buday, László ED - Gallyas, Ferenc ED - Lontay, Beáta ED - Bognár, Zita ED - Bognár, Rita ED - Szakáts, Gergely ED - Varga, Attila TI - The cytoprotective effect of kynurenic acid against simulated ischemia/reoxygenation-induced damage of cardiac cells T2 - Abstract book of Annual Meeting of the Hungarian Biochemical Society 2022 PB - Diamond Congress Kft. CY - Budapest SN - 9786155270734 PY - 2022 SP - 91 UR - https://m2.mtmt.hu/api/publication/33104875 ID - 33104875 LA - English DB - MTMT ER - TY - CHAP AU - Sárközy, Márta AU - Csont, Tamás Bálint ED - Junjie, Xiao TI - MicroRNA-based therapeutic strategies for chronic kidney disease and uremic cardiomyopathy [Chapter 28] T2 - MicroRNA PB - Elsevier Academic Press CY - London SN - 9780323897747 PY - 2022 SP - 563 EP - 600 PG - 38 DO - 10.1016/B978-0-323-89774-7.00006-6 UR - https://m2.mtmt.hu/api/publication/33032074 ID - 33032074 LA - English DB - MTMT ER - TY - JOUR AU - Szabó, Márton Richárd AU - Pipicz, Márton AU - Sárközy, Márta AU - Bruszel, Bella AU - Szabó, Zoltán AU - Csont, Tamás Bálint TI - Diet-Induced Hypercholesterolemia Leads to Cardiac Dysfunction and Alterations in the Myocardial Proteome JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 13 PG - 17 SN - 1661-6596 DO - 10.3390/ijms23137387 UR - https://m2.mtmt.hu/api/publication/32924828 ID - 32924828 N1 - Export Date: 18 October 2022 AB - Elevated blood cholesterol is a major risk factor for coronary heart disease. Moreover, direct effects on the myocardium also contribute to the adverse effects of hypercholesterolemia. Here, we investigated the effect of hypercholesterolemia on the cardiac proteome. Male Wistar rats were fed with a laboratory rodent chow supplemented with 2% cholesterol for 8 weeks to induce hypercholesterolemia. The protein expression data obtained from the proteomic characterization of left ventricular samples from normo- and hypercholesterolemic animals were subjected to gene ontology (GO) and protein interaction analyses. Elevated circulating cholesterol levels were accompanied by diastolic dysfunction in cholesterol-fed rats. The proteomic characterization of left ventricular samples revealed altered expression of 45 proteins due to hypercholesterolemia. Based on the Gene Ontology analysis, hypercholesterolemia was associated with disturbed expression of cytoskeletal and contractile proteins. Beta-actin was downregulated in the hypercholesterolemic myocardium, and established a prominent hub of the protein interaction network. Analysis of the unfiltered dataset revealed concordant downregulated expression patterns in proteins associated with the arrangement of the contractile system (e.g., cardiac-specific troponins and myosin complex), and in subunits of the mitochondrial respiratory chain. We conclude that the observed changes in the cardiac proteome may contribute to the development of diastolic dysfunction in hypercholesterolemia. LA - English DB - MTMT ER - TY - JOUR AU - Freiwan, Marah AU - Kovács, Mónika Gabriella AU - Kovács, Zsuzsanna AU - Szűcs, Gergő AU - Dinh, Hoa AU - Losonczi, Réka Hajnalka AU - Siska, Andrea AU - Kriston, András AU - Kovács, Ferenc AU - Horváth, Péter AU - Földesi, Imre AU - Cserni, Gábor AU - Dux, László AU - Csont, Tamás Bálint AU - Sárközy, Márta TI - Investigation of the Antiremodeling Effects of Losartan, Mirabegron and Their Combination on the Development of Doxorubicin-Induced Chronic Cardiotoxicity in a Rat Model JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 4 PG - 28 SN - 1661-6596 DO - 10.3390/ijms23042201 UR - https://m2.mtmt.hu/api/publication/32689754 ID - 32689754 N1 - Funding Agency and Grant Number: NKFIHNational Research, Development & Innovation Office (NRDIO) - Hungary [FK129094, GINOP-2.3.2-15-2016-00040]; Stipendium Hungaricum Program; Ministry of Human Capacities [TKP2021-EGA-32]; Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund; Stipendium Hungaricum Scholarship; New National Excellence Program of the Ministry of Human Capacities [UNKP-21-3-SZTE-97, UNKP-21-3-SZTE-98, UNKP-20-5-SZTE-166]; Janos Bolyai Research Fellowship of the Hungarian Academy of SciencesHungarian Academy of Sciences; [EFOP-3.6.3VEKOP-16-2017-00009] Funding text: This research was funded by the projects NKFIH FK129094 (to M.S., funder: National Research, Development and Innovation Office), GINOP-2.3.2-15-2016-00040 (to L.D., funder: National Research, Development and Innovation Office), Stipendium Hungaricum Program (to M.S. and L.D., funder: Tempus Public Foundation), and by the Ministry of Human Capacities TKP2021-EGA-32 (to T.C., Project no. TKP2021-EGA-32 has been implemented with the support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-EGA funding scheme.) and by Stipendium Hungaricum Program (to M.S. and L.D., funder: Tempus Public Foundation). M.F. and D.H. were supported by the Stipendium Hungaricum Scholarship (funder: Tempus Public Foundation). M.G.K., Z.Z.A.K., and M.S. were supported by the New National Excellence Program of the Ministry of Human Capacities (UNKP-21-3-SZTE-97 to M.G.K., UNKP-21-3-SZTE-98 to Z.Z.A.K., and UNKP-20-5-SZTE-166 to M.S., funder: Ministry of Human Capacities). M.S. was supported by the Janos Bolyai Research Fellowship of the Hungarian Academy of Sciences. Z.Z.A.K. and M.G.K. were supported by the EFOP-3.6.3VEKOP-16-2017-00009 project (funder: National Research, Development and Innovation Office). The APC was funded by Stipendium Hungaricum Program (funder: Tempus Public Foundation). AB - Despite the effectiveness of doxorubicin (DOXO) as a chemotherapeutic agent, dose-dependent development of chronic cardiotoxicity limits its application. The angiotensin-II receptor blocker losartan is commonly used to treat cardiac remodeling of various etiologies. The beta-3 adrenergic receptor agonist mirabegron was reported to improve chronic heart failure. Here we investigated the effects of losartan, mirabegron and their combination on the development of DOXO-induced chronic cardiotoxicity. Male Wistar rats were divided into five groups: (i) control; (ii) DOXO-only; (iii) losartan-treated DOXO; (iv) mirabegron-treated DOXO; (v) losartan plus mirabegron-treated DOXO groups. The treatments started 5 weeks after DOXO administration. At week 8, echocardiography was performed. At week 9, left ventricles were prepared for histology, qRT-PCR, and Western blot measurements. Losartan improved diastolic but not systolic dysfunction and ameliorated SERCA2a repression in our DOXO-induced cardiotoxicity model. The DOXO-induced overexpression of Il1 and Il6 was markedly decreased by losartan and mirabegron. Mirabegron and the combination treatment improved systolic and diastolic dysfunction and significantly decreased overexpression of Smad2 and Smad3 in our DOXO-induced cardiotoxicity model. Only mirabegron reduced DOXO-induced cardiac fibrosis significantly. Mirabegron and its combination with losartan seem to be promising therapeutic tools against DOXO-induced chronic cardiotoxicity. LA - English DB - MTMT ER -