@article{MTMT:32349680, title = {d,l-Methadone causes leukemic cell apoptosis via an OPRM1-triggered increase in IP3R-mediated ER Ca2+ release and decrease in Ca2+ efflux, elevating [Ca2+](i)}, url = {https://m2.mtmt.hu/api/publication/32349680}, author = {Lee, JungKwon and Rosales, Jesusa L. and Byun, Hee-Guk and Lee, Ki-Young}, doi = {10.1038/s41598-020-80520-w}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {11}, unique-id = {32349680}, issn = {2045-2322}, abstract = {The search continues for improved therapy for acute lymphoblastic leukemia (aLL), the most common malignancy in children. Recently, d,l-methadone was put forth as sensitizer for aLL chemotherapy. However, the specific target of d,l-methadone in leukemic cells and the mechanism by which it induces leukemic cell apoptosis remain to be defined. Here, we demonstrate that d,l-methadone induces leukemic cell apoptosis through activation of the mu1 subtype of opioid receptors (OPRM1). d,l-Methadone evokes IP3R-mediated ER Ca2+ release that is inhibited by OPRM1 loss. In addition, the rate of Ca2+ extrusion following d,l-methadone treatment is reduced, but is accelerated by loss of OPRM1. These d,l-methadone effects cause a lethal rise in [Ca2+](i) that is again inhibited by OPRM1 loss, which then prevents d,l-methadone-induced apoptosis that is associated with activation of calpain-1, truncation of Bid, cytochrome C release, and proteolysis of caspase-3/12. Chelating intracellular Ca2+ with BAPTA-AM reverses d,l-methadone-induced apoptosis, establishing a link between the rise in [Ca2+](i) and d,l-methadone-induced apoptosis. Altogether, our findings point to OPRM1 as a specific target of d,l-methadone in leukemic cells, and that OPRM1 activation by d,l-methadone disrupts IP3R-mediated ER Ca2+ release and rate of Ca2+ efflux, causing a rise in [Ca2+](i) that upregulates the calpain-1-Bid-cytochrome C-caspase-3/12 apoptotic pathway.}, year = {2021}, eissn = {2045-2322} } @article{MTMT:31260011, title = {Metabolic Lateralization in the Hypothalamus of Male Rats Related to Reproductive and Satiety States}, url = {https://m2.mtmt.hu/api/publication/31260011}, author = {Kiss, Dávid Sándor and Tóth, István and Jócsák, Gergely and Bartha, Tibor and Frenyó V., László and Bárány, Zoltán Balázs and Horváth, Tamás and Zsarnovszky, Attila}, doi = {10.1007/s43032-019-00131-3}, journal-iso = {REPROD SCI}, journal = {REPRODUCTIVE SCIENCES}, volume = {27}, unique-id = {31260011}, issn = {1933-7191}, year = {2020}, eissn = {1933-7205}, pages = {1197-1205}, orcid-numbers = {Tóth, István/0000-0002-0168-4753} } @article{MTMT:31399182, title = {Functional Aspects of Hypothalamic Asymmetry}, url = {https://m2.mtmt.hu/api/publication/31399182}, author = {Kiss, Dávid Sándor and Tóth, István and Jócsák, Gergely and Bárány, Zoltán Balázs and Bartha, Tibor and Frenyó V., László and Horvath, Tamas L. and Zsarnovszky, Attila}, doi = {10.3390/brainsci10060389}, journal-iso = {BRAIN SCI}, journal = {BRAIN SCIENCES}, volume = {10}, unique-id = {31399182}, abstract = {Anatomically, the brain is a symmetric structure. However, growing evidence suggests that certain higher brain functions are regulated by only one of the otherwise duplicated (and symmetric) brain halves. Hemispheric specialization correlates with phylogeny supporting intellectual evolution by providing an ergonomic way of brain processing. The more complex the task, the higher are the benefits of the functional lateralization (all higher functions show some degree of lateralized task sharing). Functional asymmetry has been broadly studied in several brain areas with mirrored halves, such as the telencephalon, hippocampus, etc. Despite its paired structure, the hypothalamus has been generally considered as a functionally unpaired unit, nonetheless the regulation of a vast number of strongly interrelated homeostatic processes are attributed to this relatively small brain region. In this review, we collected all available knowledge supporting the hypothesis that a functional lateralization of the hypothalamus exists. We collected and discussed findings from previous studies that have demonstrated lateralized hypothalamic control of the reproductive functions and energy expenditure. Also, sporadic data claims the existence of a partial functional asymmetry in the regulation of the circadian rhythm, body temperature and circulatory functions. This hitherto neglected data highlights the likely high-level ergonomics provided by such functional asymmetry.}, year = {2020}, eissn = {2076-3425}, orcid-numbers = {Tóth, István/0000-0002-0168-4753} } @article{MTMT:30758655, title = {Rapid isolation and purification of functional platelet mitochondria using a discontinuous Percoll gradient}, url = {https://m2.mtmt.hu/api/publication/30758655}, author = {Leger, Jacob L. and Jougleux, Jean-Luc and Savadogo, Fanta and Pichaud, Nicolas and Boudreau, Luc H.}, doi = {10.1080/09537104.2019.1609666}, journal-iso = {PLATELETS}, journal = {PLATELETS}, volume = {31}, unique-id = {30758655}, issn = {0953-7104}, abstract = {The isolation of mitochondria is gaining importance in experimental and clinical laboratory settings. The mitochondrion is known as the powerhouse of the cell as it produces the energy to power most cellular functions but is also involved in many cellular processes. Of interest, mitochondria and mitochondrial components (i.e. circular DNA, N-formylated peptides, cardiolipin) have been involved in several human inflammatory pathologies, such as cancer, Alzheimer's disease, Parkinson's disease, and rheumatoid arthritis. Therefore, stringent methods of isolation and purification of mitochondria are of the utmost importance in assessing mitochondrial-related diseases. While several mitochondrial isolation methods have been previously published, these techniques are aimed at yielding mitochondria from cells types other than platelets. In addition, little information is known on the number of platelet-derived microparticles that can contaminate the mitochondrial preparation or even the overall quality and integrity of the mitochondria. In this project, we provide an alternate purification method yielding mitochondria of high purity and integrity from human platelets. Using human platelets, flow cytometry and transmission electron microscopy experiments were performed to demonstrate that the Percoll gradient method yielded significantly purified mitochondria by removing platelet membrane debris. Mitochondrial respiration following the substrate-uncoupler-inhibitor-titration (SUIT) protocol was similar in both the purified and crude mitochondrial extraction methods. Finally, the cytochrome c effect and JC-1 staining did not exhibit a significant difference between the two methods, suggesting that the mitochondrial integrity was not affected. Our study suggests that the Percoll discontinuous gradient purifies viable platelet-derived mitochondria by removing platelet-derived debris, including microparticles, therefore confirming that this isolation method is ideal for studying the downstream effects of intact mitochondria in mitochondrial-related diseases.}, keywords = {DISEASE; Release; RAT-BRAIN; MUSCLE; FIBERS; CAPACITY; Respiration; CELL BIOLOGY; MICROVESICLES; Microparticle; Platelet-derived microparticles; Mitochondria isolation; mitochondria membrane integrity; Percoll extraction method}, year = {2020}, eissn = {1369-1635}, pages = {258-264} } @article{MTMT:31103047, title = {Impaired renal organic anion transport 1 (SLC22A6) and its regulation following acute myocardial infarction and reperfusion injury in rats}, url = {https://m2.mtmt.hu/api/publication/31103047}, author = {Sirijariyawat, Kungsadal and Ontawong, Atcharaporn and Palee, Siripong and Thummasorn, Savitree and Maneechote, Chayodom and Boonphanga, Oranit and Chatsudthipong, Varanuj and Chattipakorn, Nipon and Srimaroeng, Chutima}, doi = {10.1016/j.bbadis.2019.05.013}, journal-iso = {BBA-MOL BASIS DIS}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE}, volume = {1865}, unique-id = {31103047}, issn = {0925-4439}, abstract = {Acute kidney injury (AKI) is a high frequent and common complication following acute myocardial infarction (AMI). This study examined and identified the effect of AMI-induced AKI on organic anion transporter 1 (Oat1) and Oat3 transport using clinical setting of pre-renal AKI in vivo. Cardiac ischaemia (CI) and cardiac ischaemia and reperfusion (CIR) were induced in rats by 30-min left anterior descending coronary artery occlusion and 30-min occlusion followed by 120-min reperfusion, respectively. Renal hemodynamic parameters, mitochondrial function and Oat1/Oat3 expression and function were determined along with biochemical markers. Results showed that CI markedly reduced renal blood flow and pressure by approximately 40%, while these parameters were recovered during reperfusion. CI and CIR progressively attenuated renal function and induced oxidative stress by increasing plasma BUN, creatinine and malondialdehyde levels. Correspondingly, SOD, GPx, CAT mRNAs were decreased, while TNF alpha, IL1 beta, COX2, iNOS, NOX2, NOX4, and xanthine oxidase were increased. Mitochondrial dysfunction as indicated by increasing ROS, membrane depolarisation, swelling and caspase3 activation were shown. Early significant detection of AKI; KIM1, IL18, was found. All of which deteriorated para-aminohippurate transport by down-regulating Oat1 during sudden ischaemia. This consequent blunted the trafficking rate of Oat1/Oat3 transport via down-regulating PKC zeta/Akt and up-regulating PKC alpha/NF kappa B during CI and CIR. Thus, this promising study indicates that CI and CIR abruptly impaired renal Oat1 and regulatory proteins of Oat1/Oat3, which supports dysregulation of remote sensing and signalling and inter-organ/organismal communication. Oat1, therefore, could potentially worsen AKI and might be a potential therapeutic target for early reversal of such injury.}, keywords = {mitochondrial dysfunction; acute kidney injury; organic anion transporter 3; organic anion transporter 1; Acute myocardial ischemia and reperfusion; Oxidative stress}, year = {2019}, eissn = {1879-260X}, pages = {2342-2355} } @article{MTMT:27603494, title = {Lactate is oxidized outside of the mitochondrial matrix in rodent brain}, url = {https://m2.mtmt.hu/api/publication/27603494}, author = {Herbst, Eric A F and George, Mitchell A J and Brebner, Karen and Holloway, Graham P and Kane, Daniel A}, doi = {10.1139/apnm-2017-0450}, journal-iso = {APPL PHYSIOL NUTR ME}, journal = {APPLIED PHYSIOLOGY NUTRITION AND METABOLISM-PHYSIOLOGIE APPLIQUEE NUTRITION}, volume = {43}, unique-id = {27603494}, issn = {1715-5312}, year = {2018}, eissn = {1715-5320}, pages = {467-474} }