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 - 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 - 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 - Sárközy, Márta AU - Márványkövi, Fanni AU - Szűcs, Gergő AU - Kovács, Zsuzsanna AU - Szabó, Márton Richárd AU - Molnár-Gáspár, Renáta AU - Siska, Andrea AU - Kővári, Bence AU - Cserni, Gábor AU - Földesi, Imre AU - Csont, Tamás Bálint TI - Ischemic preconditioning protects the heart against ischemia-reperfusion injury in chronic kidney disease in both males and females JF - BIOLOGY OF SEX DIFFERENCES J2 - BIOL SEX DIFFER VL - 12 PY - 2021 IS - 1 PG - 20 SN - 2042-6410 DO - 10.1186/s13293-021-00392-1 UR - https://m2.mtmt.hu/api/publication/32191180 ID - 32191180 N1 - Funding Agency and Grant Number: Ministry of Human Capacities [20391-3/2018/FEKUSTRAT, TSZ:34232-3/2016/INTFIN]; New National Excellence Program of the Ministry of Human Capacities [UNKP-20-5-SZTE-166, UNKP-19-4-SZTE-89, UNKP-19-2-SZTE-77, UNKP-20-4-SZTE-150, UNKP19-3-SZTE-269]; Janos Bolyai Research Fellowship of the Hungarian Academy of SciencesHungarian Academy of Sciences; Szeged Scientists Academy Program; [GINOP-2.3.2-152016-00040]; [NKFIH K115990]; [NKFIH FK129094]; [EFOP-3.6.2-16-2017-00006] Funding text: The work and publication were supported by the projects GINOP-2.3.2-152016-00040, NKFIH K115990, NKFIH FK129094, EFOP-3.6.2-16-2017-00006 (LIVE LONGER), and by the Ministry of Human Capacities (20391-3/2018/FEKUSTRAT). MS, FMM, RG, and MRS were supported by the New National Excellence Program of the Ministry of Human Capacities (UNKP-20-5-SZTE-166, UNKP-19-4-SZTE-89, UNKP-19-2-SZTE-77, UNKP-20-4-SZTE-150 and UNKP19-3-SZTE-269). MS is supported by the Janos Bolyai Research Fellowship of the Hungarian Academy of Sciences. FMM was supported by the Szeged Scientists Academy Program. The Szeged Scientists Academy Program of the Foundation for the Future of Biomedical Sciences in Szeged is implemented with the support of the Ministry of Human Capacities (TSZ:34232-3/2016/INTFIN). LA - English DB - MTMT ER - TY - JOUR AU - Mitra, Argha AU - Sarkar, Arijit AU - Szabó, Márton Richárd AU - Borics, Attila TI - Correlated Motions of Conserved Polar Motifs Lay out a Plausible Mechanism of G Protein-Coupled Receptor Activation JF - BIOMOLECULES J2 - BIOMOLECULES VL - 11 PY - 2021 IS - 5 PG - 16 SN - 2218-273X DO - 10.3390/biom11050670 UR - https://m2.mtmt.hu/api/publication/32048186 ID - 32048186 AB - Recent advancements in the field of experimental structural biology have provided high-resolution structures of active and inactive state G protein-coupled receptors (GPCRs), a highly important pharmaceutical target family, but the process of transition between these states is poorly understood. According to the current theory, GPCRs exist in structurally distinct, dynamically interconverting functional states of which populations are shifted upon binding of ligands and intracellular signaling proteins. However, explanation of the activation mechanism, on an entirely structural basis, gets complicated when multiple activation pathways and active receptor states are considered. Our unbiased, atomistic molecular dynamics simulations of the mu opioid receptor (MOP) revealed that transmission of external stimulus to the intracellular surface of the receptor is accompanied by subtle, concerted movements of highly conserved polar amino acid side chains along the 7th transmembrane helix. This may entail the rearrangement of polar species and the shift of macroscopic polarization in the transmembrane domain, triggered by agonist binding. Based on our observations and numerous independent indications, we suggest amending the widely accepted theory that the initiation event of GPCR activation is the shift of macroscopic polarization between the ortho- and allosteric binding pockets and the intracellular G protein-binding interface. LA - English DB - MTMT ER - TY - JOUR AU - Gopisetty, Mohana Krishna AU - Adamecz, Dóra Izabella AU - Nagy, Ferenc István AU - Baji, Ádám AU - Lathira, Vasiliki AU - Szabó, Márton Richárd AU - Molnár-Gáspár, Renáta AU - Csont, Tamás Bálint AU - Nagyné Frank, Éva AU - Csontné Kiricsi, Mónika TI - Androstano-arylpyrimidines. novel small molecule inhibitors of MDR1 for sensitizing multidrug-resistant breast cancer cells TS - novel small molecule inhibitors of MDR1 for sensitizing multidrug-resistant breast cancer cells JF - EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES J2 - EUR J PHARM SCI VL - 156 PY - 2021 PG - 11 SN - 0928-0987 DO - 10.1016/j.ejps.2020.105587 UR - https://m2.mtmt.hu/api/publication/31623181 ID - 31623181 LA - English DB - MTMT ER - TY - JOUR AU - Szabó, Márton Richárd AU - Pipicz, Márton AU - Csont, Tamás Bálint AU - Csonka, Csaba TI - Modulatory effect of myokines on reactive oxygen species in ischemia/reperfusion JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 21 PY - 2020 IS - 24 PG - 26 SN - 1661-6596 DO - 10.3390/ijms21249382 UR - https://m2.mtmt.hu/api/publication/31789683 ID - 31789683 AB - There is a growing body of evidence showing the importance of physical activity against acute ischemic events in various organs. Ischemia/reperfusion injury (I/R) is characterized by tissue damage as a result of restriction and subsequent restoration of blood supply to an organ. Oxidative stress due to increased reactive oxygen species formation and/or insufficient antioxidant defense is considered to play an important role in I/R. Physical activity not only decreases the general risk factors for ischemia but also confers direct anti-ischemic protection via myokine production. Myokines are skeletal muscle-derived cytokines, representing multifunctional communication channels between the contracting skeletal muscle and other organs through an endocrine manner. In this review, we discuss the most prominent members of the myokines (i.e., brain-derived neurotrophic factor (BDNF), cathepsin B, decorin, fibroblast growth factors-2 and-21, follistatin, follistatin-like, insulin-like growth factor-1; interleukin-6, interleukin-7, interleukin-15, irisin, leukemia inhibitory factor, meteorin-like, myonectin, musclin, myostatin, and osteoglycin) with a particular interest in their potential influence on reactive oxygen and nitrogen species formation or antioxidant capacity. A better understanding of the mechanism of action of myokines and particularly their participation in the regulation of oxidative stress may widen their possible therapeutic use and, thereby, may support the fight against I/R. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. LA - English DB - MTMT ER - TY - CHAP AU - Szabó, Márton Richárd AU - Molnár-Gáspár, Renáta AU - Pipicz, Márton AU - Zsindely, Nóra AU - Diószegi, Petra AU - Sárközy, Márta AU - Bodai, László AU - Csont, Tamás Bálint ED - Rakonczay, Zoltán ED - Kiss, Lóránd TI - Development of diet-induced hypercholesterolemia is associated with alterations in cardiac gene expression profile T2 - Proceedings of the EFOP-3.6.2-16-2017-00006 (LIVE LONGER) project PB - University of Szeged CY - Szeged SN - 9789633067642 PY - 2020 SP - 72 EP - 72 PG - 1 UR - https://m2.mtmt.hu/api/publication/31647861 ID - 31647861 LA - English DB - MTMT ER - TY - JOUR AU - Szabó, Márton Richárd AU - Molnár-Gáspár, Renáta AU - Pipicz, Márton AU - Zsindely, Nóra AU - Diószegi, Petra AU - Sárközy, Márta AU - Bodai, László AU - Csont, Tamás Bálint TI - Hypercholesterolemia Interferes with Induction of miR-125b-1-3p in Preconditioned Hearts JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 21 PY - 2020 IS - 11 PG - 11 SN - 1661-6596 DO - 10.3390/ijms21113744 UR - https://m2.mtmt.hu/api/publication/31330253 ID - 31330253 N1 - Cited By :5 Export Date: 20 June 2022 LA - English DB - MTMT ER -