Number of the records: 1
The aggressiveness of succinate dehydrogenase subunit B-deficient chromaffin cells is reduced when their bioelectrical properties are restored by glibenclamide
- 1.
SYSNO ASEP 0583191 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title The aggressiveness of succinate dehydrogenase subunit B-deficient chromaffin cells is reduced when their bioelectrical properties are restored by glibenclamide Author(s) Amore, F. (IT)
Garella, R. (IT)
Santi, A. (IT)
Guasti, D. (IT)
Martinelli, S. (IT)
Canu, L. (IT)
Bani, D. (IT)
Neužil, Jiří (BTO-N) RID
Maggi, M. (IT)
Squecco, R. (IT)
Rapizzi, E. (IT)Number of authors 11 Article number e230167 Source Title Endocrine-Related Cancer - ISSN 1351-0088
Roč. 30, č. 10 (2023)Number of pages 16 s. Language eng - English Country GB - United Kingdom Keywords sensitive potassium channels ; k-atp channels ; ion channels ; growth-factor ; complex-ii ; microenvironment Subject RIV FB - Endocrinology, Diabetology, Metabolism, Nutrition OECD category Endocrinology and metabolism (including diabetes, hormones) R&D Projects GX21-04607X GA ČR - Czech Science Foundation (CSF) Method of publishing Limited access Institutional support BTO-N - RVO:86652036 UT WOS 001156979200004 EID SCOPUS 85168802191 DOI 10.1530/ERC-23-0167 Annotation Pheochromocytomas/paragangliomas (PPGLs) are neuroendocrine tumours, mostly resulting from mutations in predisposing genes. Mutations of succinate dehydrogenase (SDH) subunit B (SDHB) are associated with high probability of metastatic disease. Since bioelectrical properties and signalling in cancer are an emerging field, we investigated the metabolic, functional and electrophysiological characteristics in human succinate dehydrogenase subunit B (SDHB)-deficient pheochromocytoma cells. These cells exhibited reduced SDH function with elevated succinate-to-fumarate ratio and reduced intracellular ATP levels. The analysis of membrane passive properties revealed a more hyperpolarized membrane potential and a lower cell capacitance of SDHB-deficient cells compared to the parental ones. These bioelectrical changes were associated with reduced proliferation and adhesion capacity of SDHB-deficient cells. Only in SDHB-deficient cells, we also observed an increased amplitude of potassium currents suggesting an activation of ATP-sensitive potassium channels (K-ATP). Indeed, exposure of the SDHB-deficient cells to glibenclamide, a specific K-ATP inhibitor, or to ATP caused normalization of potassium current features and altered proliferation and adhesion. In this work, we show for the first time that reduced intracellular ATP levels in SDHB-deficient chromaffin cells impaired cell bioelectrical properties, which, in turn, are associated with an increased cell aggressiveness. Moreover, we first ever demonstrated that glibenclamide not only reduced the outward potassium currents in SDHB-deficient cells but increased their growth capacity, reduced their ability to migrate and shifted their phenotype towards one more similar to that of parental one. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2024 Electronic address https://erc.bioscientifica.com/view/journals/erc/30/10/ERC-23-0167.xml
Number of the records: 1