PhD Scientific Days 2025

Poster Session II. - B: Molecular Medicine

Regulation of Human Stearoyl-CoA Desaturase Expression Induced by Hypoxia

Name of the presenter

Orosz Gabriella

Institute/workplace of the presenter

Semmelweis University, Department of Molecular Biology, Budapest, Hungary

Authors

Gabriella Orosz¹, Veronika Zámbó¹, Éva Kereszturi¹

1: Semmelweis University, Department of Molecular Biology, Budapest, Hungary

Text of the abstract

Stearoyl-CoA desaturase (SCD) enzymes are critical in maintaining cellular lipid homeostasis by facilitating the formation of unsaturated fatty acids. The two human isoforms, SCD1 and SCD5, are regulated at multiple levels. Emerging evidence suggests that hypoxic conditions also impact the regulatory mechanisms of SCDs in addition to the influence of nutrient supply.
Hypoxia-inducible factor 1-alpha (Hif1α), the central element of the hypoxic signaling pathway, modulates the expression of several genes to facilitate cellular adaptation to oxygen deficiency, including the regulation of a proto-oncogene, ETS1 transcription factor (TF).
This study aims to elucidate the regulatory mechanisms underlying the hypoxia-sensitive expression of SCD1 and SCD5, alongside the potential impact of genetic polymorphisms, using an in vitro cell model.
In silico analysis of SCD1 and SCD5 promoters revealed multiple ETS1 binding sites and a single Hif1α consensus sequence. Identified genetic variants were observed to disrupt ETS1 binding sites, potentially altering transcriptional regulation.
Hypoxic conditions were simulated using 100 µM desferrioxamine (DFO) treatment of HEK293T and SK-N-FI neuroblastoma cells for 4 to 24 hours, with subsequent monitoring of expression levels via qPCR and immunoblotting. Additionally, promoter activities of wild-type and polymorphic variants of SCD1 and SCD5 were quantified using a luciferase reporter system under normoxic and hypoxic conditions. Results demonstrated a significant increase in ETS1, SCD1, and SCD5 expression at both mRNA and protein levels following DFO treatment.
Under normoxic conditions, promoter activity was significantly reduced in variants disrupting ETS1 binding sites relative to wild-type promoters.
The results of this study provide new insights into the regulation of SCD1 and SCD5 in hypoxic conditions and highlight the impact of reduced oxygen levels on the lipid composition of cells. Additionally, they illustrate the influence of individual genetic variants on these processes.
This work was supported by FK_138115, PD_142709, and EKÖP-2024-II grants.