The aggressiveness of succinate dehydrogenase subunit B-deficient chromaffin cells is reduced when their bioelectrical properties are restored by glibenclamide

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F23%3A00583191" target="_blank" >RIV/86652036:_____/23:00583191 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/23:10476039

Result on the web

<a href="https://erc.bioscientifica.com/view/journals/erc/30/10/ERC-23-0167.xml" target="_blank" >https://erc.bioscientifica.com/view/journals/erc/30/10/ERC-23-0167.xml</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1530/ERC-23-0167" target="_blank" >10.1530/ERC-23-0167</a>

Result language

angličtina

Original language name

The aggressiveness of succinate dehydrogenase subunit B-deficient chromaffin cells is reduced when their bioelectrical properties are restored by glibenclamide

Original language description

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.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30202 - Endocrinology and metabolism (including diabetes, hormones)

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Endocrine-Related Cancer

ISSN

1351-0088

e-ISSN

1479-6821

Volume of the periodical

30

Issue of the periodical within the volume

10

Country of publishing house

GB - UNITED KINGDOM

Number of pages

16

Pages from-to

e230167

UT code for WoS article

001156979200004

EID of the result in the Scopus database

2-s2.0-85168802191