ECE2021 Presented Eposters Presented ePosters 1: Adrenal and Cardiovascular Endocrinology (8 abstracts)
ARMC5 modifies cell redox state to regulate steroidogenesis and lipid metabolism in the adrenal cortex
Isadora Pontes Cavalcante 1 , Marthe Rizk-Rabin 1 , Karine Perlemoine 1 , Christopher Ribes 1 , Jerome Bertherat 1 , 2 & Bruno Ragazzon 1
1Cochin Institute, EMD Department, France; 2APHP, Cochin Hospital, Department of Endocrinology, Paris, France
Background
ARMC5 is a putative tumor suppressor gene that is frequently mutated in primary bilateral macronodular adrenal hyperplasia (PBMAH), a rare cause of Cushing’s syndrome. The function of ARMC5 is poorly known, aside the fact that it regulates cell apoptosis and adrenal steroidogenesis in by mechanisms still unknown. Tumor suppressor genes play an important role in oxidative stress.
Methods
In this study we used as model the adrenocortical carcinoma cell line H295R. In order to investigate ARMC5 response to stress, cells were treated with Menadione and reactive oxygen species (ROS) production was measured by Cellrox assays with flow cytometry. Oxidative response genes and steroidogenic enzymes expression were investigated by qPCR, whereas p38 phosphorylation was investigated by western blotting.
Results
ARMC5 protein is differentially regulated in response to menadione-induced stress in H295R adrenocortical cells. Moreover, ARMC5 depletion increases total intracellular ROS production (P <0.05) and causes an imbalanced transcription of pro and anti-oxidant genes leading to increased phosphorylation of p38 (P <0.05). ROS production and p38 pathway activation alter steroidogenesis. These effects are partially reversed by the anti-oxidant compound N-acetylcysteine (NAC) or the p38 inhibitor (SB203580). Finally, ARMC5 depletion leads to lipid droplets accumulation in the cell cytoplasm, associated to increased expression of APOE gene, important for cholesterol esterification.
Conclusion
Altogether, this study describes a new function of ARMC5 as regulator of the redox homeostasis and lipid metabolism in adrenocortical cells.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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