PhD Scientific Days 2024

Poster Session T - Cardiovascular Medicine and Research 3.

The Effects of 25-hydroxycholesterol on Signaling Events in Vascular Smooth Muscle Cells

Előadó neve

Kovács, Kinga Bernadett, MSc

Neptun code

TTZS32

Előadó munkahelye

Department of Physiology, Semmelweis University

Előadó telefonszáma

+36706638796

Előadó e-mail címe

kovacs.kinga@phd.semmelweis.hu

Az előadás címe

The Effects of 25-hydroxycholesterol on Signaling Events in Vascular Smooth Muscle Cells

Szerző(k) neve és munkahelye

Kinga Bernadett Kovács¹, László Hunyady^1,2, András Balla^1,3

1: Department of Physiology, Semmelweis University
2: Institute of Molecular Life Sciences, Research Centre for Natural Sciences
3: HUN-REN–SU Molecular Physiology Research Group

Bemutatás módja

Poszter

Szekció

Poster Session T - Cardiovascular Medicine and Research 3.

Language of the presentation

English

Preferred session

Cardiovascular Medicine and Research

Összefoglaló szövege

Cholesterol-25-hydroxylase (CH25H) catalyzes the production of 25-hydroxycholesterol (25-HC). 25-HC is both a cholesterol metabolite and a bioactive molecule. 25-HC was shown to be a mediator of immunological processes and an actor in the pathology of atherosclerosis. Our group found that angiotensin II promotes Ch25h upregulation and 25-HC production in vascular smooth muscle cells (VSMCs).
Our aim is to explore the effects of 25-HC on signalization in VSMCs.
Primary rat VSMCs and A7R5 VSMC line were used during the course of the study. VSMCs were treated with 25-HC and subjected to Western blot procedure to detect phosphorylation of focal adhesion kinase (FAK). Ras activation in A7R5 cells was investigated with bioluminescence resonance energy transfer (BRET).
VSMCs showed a significantly increased FAK phosphorylation on the Y397 residue when treated with 25-HC (50 µM) for 1 hour compared to control group treated with vehicle (ethanol). We found that even at a concentration of 5 µM 25-HC promoted FAK phosphorylation.
To examine Ras activity A7R5 cells recieved 25-HC (50 µM) treatment then were stimulated with epidermal growth factor (EGF). Compared to the ethanol-treated group Ras activation was less sustained after a 6 hour long 25-HC treatment.
Intriguingly, 25-HC induced the activation of FAK in VSMC. Literature data shows that 25-HC activates FAK-related pathways in macrophages by binding integrins. However, there had been no information of such process in VSMCs. Furthermore, we showed that 25-HC treatment was able to interfere with EGF signalization, as indicated by the alteration of Ras activity after 25-HC treatment. The exact mechanism of action cannot be confidently concluded based on our BRET data. Other studies found that 25-HC in the plasma membrane can modify membrane fluidity and thus lipid rafts, which might explain alterations of receptor signalizations.
Our present study showed for the first time that 25-HC promotes FAK phosphorylation in VSMCs, and is able to influence EGF signalization. These findings suggest that 25-HC released by VSMCs has the potential to exert regulatory actions on signaling events in VSMC.
Funds:
Semmelweis 250+ Excellence PhD Scholarship
SUPPORTED BY THE ÚNKP-23-3-II NEW NATIONAL EXCELLENCE PROGRAM OF THE MINISTRY FOR CULTURE AND INNOVATION FROM THE SOURCE OF THE NATIONAL RESEARCH, DEVELOPMENT AND INNOVATION FUND

University

Semmelweis University

Supervisor

András Balla

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6841

Start

16:15

End

16:18