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6 záznamů v Medvik Filtry

Článek

Succinate Mediates Tumorigenic Effects via Succinate Receptor 1: Potential for New Targeted Treatment Strategies in Succinate Dehydrogenase Deficient Paragangliomas

Matlac, Dieter M
Autor Matlac, Dieter M Neuroendocrine Oncology and Metabolism, Medical Department I, Center of Brain, Behavior, and Metabolism, University Medical Center Schleswig-Holstein Lübeck, Lübeck, Germany
Hadrava Vanova, Katerina
Autor Hadrava Vanova, Katerina Institute of Biotechnology, Czech Academy of Sciences, Prague-West, Czechia Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
Bechmann, Nicole
Autor Bechmann, Nicole Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
Richter, Susan
Autor Richter, Susan Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
Folberth, Julica
Autor Folberth, Julica Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany
Ghayee, Hans K
Autor Ghayee, Hans K Department of Medicine, Division of Endocrinology, University of Florida and Malcom Randall VA Medical Center, Gainesville, FL, United States
Ge, Guang-Bo
Autor Ge, Guang-Bo Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Abunimer, Luma
Autor Abunimer, Luma Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
Wesley, Robert
Autor Wesley, Robert Neuroendocrine Oncology and Metabolism, Medical Department I, Center of Brain, Behavior, and Metabolism, University Medical Center Schleswig-Holstein Lübeck, Lübeck, Germany Institute of Biotechnology, Czech Academy of Sciences, Prague-West, Czechia Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany Department of Medicine, Division of Endocrinology, University of Florida and Malcom Randall VA Medical Center, Gainesville, FL, United States Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany Department of Biomedical Engineering, Centre for Public Health Genomics, University of Virginia, Charlottesville, VA, United States Division of Endocrinology 471, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands Hereditary Endocrine Cancer Group, Human Cancer Genetics Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain Laboratory of Surgical Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States Radboud University, Nijmegen, Netherlands Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States School of Medical Science, Griffith University, Southport, QLD, Australia
Aherrahrou, Redouane
Autor Aherrahrou, Redouane Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany Department of Biomedical Engineering, Centre for Public Health Genomics, University of Virginia, Charlottesville, VA, United States

Frontiers in endocrinology. 2021 ; 12 (-) : 589451. [pub] 20210312

Front. endocrinol.
ISSN 1664-2392
Medvik
Zdroj

Paragangliomas and pheochromocytomas (PPGLs) are chromaffin tumors associated with severe catecholamine-induced morbidities. Surgical removal is often curative. However, complete resection may not be an option for patients with succinate dehydrogenase subunit A-D (SDHx) mutations. SDHx mutations are associated with a high risk for multiple recurrent, and metastatic PPGLs. Treatment options in these cases are limited and prognosis is dismal once metastases are present. Identification of new therapeutic targets and candidate drugs is thus urgently needed. Previously, we showed elevated expression of succinate receptor 1 (SUCNR1) in SDHB PPGLs and SDHD head and neck paragangliomas. Its ligand succinate has been reported to accumulate due to SDHx mutations. We thus hypothesize that autocrine stimulation of SUCNR1 plays a role in the pathogenesis of SDHx mutation-derived PPGLs. We confirmed elevated SUCNR1 expression in SDHx PPGLs and after SDHB knockout in progenitor cells derived from a human pheochromocytoma (hPheo1). Succinate significantly increased viability of SUCNR1-transfected PC12 and ERK pathway signaling compared to control cells. Candidate SUCNR1 inhibitors successfully reversed proliferative effects of succinate. Our data reveal an unrecognized oncometabolic function of succinate in SDHx PPGLs, providing a growth advantage via SUCNR1.

MeSH
feochromocytom farmakoterapie enzymologie genetika metabolismus MeSH
krysa rodu rattus MeSH
kyselina jantarová metabolismus MeSH
lidé MeSH
mutace MeSH
myši MeSH
paragangliom farmakoterapie enzymologie genetika metabolismus MeSH
podjednotky proteinů genetika metabolismus MeSH
receptory spřažené s G-proteiny antagonisté a inhibitory genetika metabolismus MeSH
sukcinátdehydrogenasa nedostatek genetika MeSH
zvířata MeSH
Check Tag
krysa rodu rattus MeSH
lidé MeSH
myši MeSH
zvířata MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH
Research Support, N.I.H., Intramural MeSH

Článek

Diabetes mellitus a arteriální hypertenze [Diabetes und Hypertonie]

Medicína po promoci. 2010 ; 11 (1) : 17-24.

ISSN 1212-9445
Medvik
Zdroj

Současný výskyt diabetu a arteriální hypertenze potencuje kardiovaskulární riziko. Průkaz mikroalbuminurie představuje u diabetiků důležitý nezávislý ukazatel zvýšeného rizika morbidity a mortality. Progresi diabetické nefropatie ovlivňuje rozhodujícím způsobem arteriální hypertenze. Základem léčby pacientů s diabetem 2. typu a s arteriální hypertenzí jsou intervence týkající se životního stylu. Obecně platí, že s farmakoterapií antihypertenzivy by se mělo začít při hodnotách krevního tlaku nad 140/90 mm Hg, přičemž cílová hodnota krevního tlaku je nižší než 130/80 mm Hg, při manifestní diabetické nefropatii nižší než 125/75 mm Hg. K nejdůležitějším terapeutickým cílům u pacientů s diabetickou nefropatií patří zpomalení progrese albuminurie, oddálení stadia selhání ledvin a snížení vysokého rizika kardiálních a cerebrovaskulárních příhod. Antihypertenzivy první volby jsou inhibitory angiotensin konvertujícího enzymu (ACE ) a blokátory angiotensinových receptorů, které zpomalují progresi nefropatie účinněji než léčiva z jiných skupin, a proto by měly být v kombinační léčbě arteriální hypertenze vždy zastoupeny. Obezita viscerálního typu vyvolává prostřednictvím různých neuroendokrinních mechanismů zvýšenou aktivaci systému renin-angiotensin-aldosteron a vzestup sympatického tonu v ledvinách i v rezistenčních tepnách.