PhD Scientific Days 2022

Clinical Medicine VII. (Poster discussion will take place in the Aula during the Coffee Break)

The Sigma-1 Receptor-Mediated Role of 17β-estradiol in in vitro models of Renal Ischemia Reperfusion Injury

Előadó neve

Saeed, Adar, MSc

Előadó munkahelye

1st department of pediatrics, MTA Center of Excellence, Semmelweis university

Előadó telefonszáma

203161471

Előadó e-mail címe

adaramedi992@gmail.com

Az előadás címe

The Sigma-1 Receptor-Mediated Role of 17β-estradiol in in vitro models of Renal Ischemia Reperfusion Injury

Szerző(k) neve és munkahelye

Adar Saeed1,2, Akos Toth1, 2, Shaaban Kamil1, 2, Dora Bianka Balogh1, 2, Apor Veres-Szekely2, 3, Judit Hodrea1, 2, Attila J. Szabo2, Adam Hosszu1, 2, Andrea Fekete1, 2

1MTA-SE “Lendület” Diabetes Research Group, Budapest, Hungary
21st Department of Pediatrics, MTA Center of Excellence Semmelweis University, Budapest, Hungary
3ELKH-SE Pediatrics and Nephrology Research Group, Budapest, Hungary

Bemutatás módja

Poszter

Szekció

Clinical Medicine VII. (Poster discussion will take place in the Aula during the Coffee Break)

Language of the presentation

English

Preferred session

Clinical Medicine

Összefoglaló szövege

Introduction: It is a known phenomenon that females enjoy a reduced susceptibility to renal ischemia/reperfusion injury (IRI) compared to males. We recently showed that Sigma-1 receptor (S1R) activation by 17β-estradiol in female rats is protective in IRI by enhancing the heat shock response.
Aims: In the present study we aimed to investigate the molecular pathways induced by the 17β-estradiol mediated activation of sigma-1 receptor in various in vitro models.
Methods: Human renal proximal tubular epithelial cells (HK-2) were treated with 17β-estradiol (E2) for 24 h. The treated HK-2 cells were stimulated by layering mineral oil (45 min at 37C), hydrogen peroxide (H2O2, 500 μM, 2 h) and Tunicamycin (Tm, 5 nM, 6 h) to induce the hypoxia stress, oxidative stress and ER stress resp.
Results: Hypoxic injury of HK-2 cells was confirmed by elevated HIF-1α protein levels and HMOX1 gene expression. Both HIF-1 and HMOX1 levels were decreased following E2 therapy, indicating reduced hypoxia. Cell proliferation markers, Proliferating cell nuclear antigen (PCNA) and Ki67 are reduced tendency after hypoxia, which was counteracted by E2. Both proinflammatory cytokines IL-1β and IL-6 increased after hypoxia and E2 treatment minimized IL-1β expression. H2O2 induced the oxidative stress by elevating HMOX1, p53-mediated apoptotic pathway and inflammatory cytokines which were abated by E2 treatment. CHOP expression increased sevenfold following tunicamycin (Tm) therapy, but was unaffected by E2. PCNA and Ki67 levels were lowered by ER stress but were restored to control levels following E2 treatment. ER stress enhanced acute phase inflammatory cytokines.
Conclusions: We identified S1R activation by E2 as a possible mediator of protective mechanisms against hypoxic- oxidative- and ER-stress in renal proximal tubular cells. Based on our data S1R activation could provide a new option for renoprotective therapy.

Funding: OTKA PD-131637; FK-124491; LP2021-3/2021; PC2022-8/2022; TKP2021-EGA-24; UN2101GYK; KDP-2020/1019145

University and Doctoral School

Other, please specify in the next box

Other university and doctoral school, not listed above

Semmelweis University, Doctoral School of Clinical Medicine

Supervisor

Fekete Andrea

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

6884

Start

13:55

End

14:00

Authors (legacy)

Adar Saeed1,2, Akos Toth1, 2, Shaaban Kamil1, 2, Dora Bianka Balogh1, 2, Apor Veres-Szekely2, 3, Judit Hodrea1, 2, Attila J. Szabo2, Adam Hosszu1, 2, Andrea Fekete1, 2

1MTA-SE “Lendület” Diabetes Research Group, Budapest, Hungary
21st Department of Pediatrics, MTA Center of Excellence Semmelweis University, Budapest, Hungary
3ELKH-SE Pediatrics and Nephrology Research Group, Budapest, Hungary