PhD Scientific Days 2022

Molecular Sciences III. (Poster discussion will take place on the terrace of the room during the Coffee Break)

LPA Induced Death Receptor 6 Expression in Endothelial Cells

Előadó neve

Dr. Major, Enikő

Előadó munkahelye

Institute of Translational Medicine, Semmelweis University

Előadó telefonszáma

+36305342593

Előadó e-mail címe

major.eniko@med.semmelweis-univ.hu

Az előadás címe

LPA Induced Death Receptor 6 Expression in Endothelial Cells

Szerző(k) neve és munkahelye

Enikő Major1, Johnny Louis Castillo1, Gábor Tigyi2, Zoltán Benyó1
1 Institute of Translational Medicine, Semmelweis University, Budapest, Hungary
2 Department of Physiology, University of Tennessee Health Science Center, Memphis, USA

Bemutatás módja

Poszter

Szekció

Molecular Sciences III. (Poster discussion will take place on the terrace of the room during the Coffee Break)

Language of the presentation

English

Preferred session

Molecular Sciences

Összefoglaló szövege

Introduction: Lysophosphatidic acid (LPA) is a bioactive lipid. Its effects are mediated by 6 subtypes of LPA receptors, which are also expressed in various cells of the vessels as well as in tumor cells. It is known that tumor cells can produce LPA as well as induce its generation from activated platelets. Interestingly, autotaxin, a lysophospholipase enzyme D that catalyzes LPA synthesis, was first isolated from melanoma, where its very high expression plays a role in tumor metastasis and progression. Tumor cells can induce endothelial cell necroptosis through the DR6 (death receptor 6) receptor, resulting in tumor cell extravasation. We hypothesized that LPA induce the expression of DR6 in cultured endothelial cells.
Methods: To investigate the effect on DR6 expression of endothelial cells, human umbilical vein endothelial cells (HUVEC), human lung microvascular endothelial cells (HMVEC-L), and mouse lung microvascular endothelial cells (MLMVEC) were treated with 0.3, 1, 3, or 10 uM 18:1 LPA for 1 hour. For analyzing the kinetics of DR6 expression induced by LPA, cells were harvested 1, 3, 6, 9, 12, or 24 hours after the beginning of the 1-hour treatment. DR6 expression was measured both by qPCR and by immunocytochemistry or flow cytometry. In each cell line, the expression of LPA receptor subtypes were determined using qPCR.
Results: Under physiological conditions, the DR6 expression of endothelial cells is low. We found, that LPA induced immediate-early-type upregulation of DR6 gene expression. The 1-hour incubation with LPA resulted in dose-dependent upregulation of DR6 gene expression in mouse and human endothelial cell lines. The cell membrane-associated DR6 protein expression reached its maximum at 6 hours. The LPA receptor expression of the mouse and human endothelial cells different. The MLMVECs express LPAR 1, 2, 4, and 6, whereas the HMVEC-L express LPAR 1, 2, 3, 5 and HUVECs express LPAR 1,2 and 5.
Conclusion: Our results indicate that LPA can induce death receptor 6 that might play a role in necroptosis.
This study was supported by NKFIH K-125174, K-135683 and K-139230 as well as by 2020-1.1.6-JÖVŐ-2021-00010, TKP2021-EGA-25 and EFOP-3.6.3-VEKOP-16-2017-00009 grants and by the Richter Gedeon Talentum Foundation.

University and Doctoral School

Semmelweis University, Doctoral School of Theoretical and Translational Medicine

Supervisor

Prof. Dr. Zoltán Benyó

Publication of my abstract

I do not 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

4810

Start

13:10

End

13:15

Authors (legacy)

Enikő Major1, Johnny Louis Castillo1, Gábor Tigyi2, Zoltán Benyó1
1 Institute of Translational Medicine, Semmelweis University, Budapest, Hungary
2 Department of Physiology, University of Tennessee Health Science Center, Memphis, USA