In vitro study of interaction of 17β-hydroxysteroid dehydrogenase type 10 and cyclophilin D and its potential implications for Alzheimer’s disease

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F19%3A43920020" target="_blank" >RIV/00023752:_____/19:43920020 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/s41598-019-53157-7" target="_blank" >https://www.nature.com/articles/s41598-019-53157-7</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-019-53157-7" target="_blank" >10.1038/s41598-019-53157-7</a>

Jazyk výsledku

angličtina

Název v původním jazyce

In vitro study of interaction of 17β-hydroxysteroid dehydrogenase type 10 and cyclophilin D and its potential implications for Alzheimer’s disease

Popis výsledku v původním jazyce

In early stages of Alzheimer’s disease (AD), amyloid-β (Aβ) accumulates in neuronal mitochondria where it interacts with a number of biomolecules including 17beta-hydroxysteroide dehydrogenase 10 (17β-HSD10) and cyclophilin D (cypD). It has been hypothesized that 17β-HSD10 interacts with cypD preventing it from opening mitochondrial permeability transition pores and that its regulation during AD may be affected by the accumulation of Aβ. In this work, we demonstrate for the first time that 17β-HSD10 and cypD form a stable complex in vitro. Furthermore, we show that factors, such as pH, ionic environment and the presence of Aβ, affect the ability of 17β-HSD10 to bind cypD. We demonstrate that K+ and Mg2+ ions present at low levels may facilitate this binding. We also show that different fragments of Aβ (Aβ1–40 and Aβ1–42) affect the interaction between 17β-HSD10 and cypD differently and that Aβ1–42 (in contrast to Aβ1–40) is capable of simultaneously binding both 17β-HSD10 and cypD in a tri-complex.

Název v anglickém jazyce

In vitro study of interaction of 17β-hydroxysteroid dehydrogenase type 10 and cyclophilin D and its potential implications for Alzheimer’s disease

Popis výsledku anglicky

In early stages of Alzheimer’s disease (AD), amyloid-β (Aβ) accumulates in neuronal mitochondria where it interacts with a number of biomolecules including 17beta-hydroxysteroide dehydrogenase 10 (17β-HSD10) and cyclophilin D (cypD). It has been hypothesized that 17β-HSD10 interacts with cypD preventing it from opening mitochondrial permeability transition pores and that its regulation during AD may be affected by the accumulation of Aβ. In this work, we demonstrate for the first time that 17β-HSD10 and cypD form a stable complex in vitro. Furthermore, we show that factors, such as pH, ionic environment and the presence of Aβ, affect the ability of 17β-HSD10 to bind cypD. We demonstrate that K+ and Mg2+ ions present at low levels may facilitate this binding. We also show that different fragments of Aβ (Aβ1–40 and Aβ1–42) affect the interaction between 17β-HSD10 and cypD differently and that Aβ1–42 (in contrast to Aβ1–40) is capable of simultaneously binding both 17β-HSD10 and cypD in a tri-complex.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/NV16-27611A" target="_blank" >NV16-27611A: Interakce intracelulárního amyloidu beta a diagnostika Alzheimerovy nemoci</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Scientific Reports

ISSN

2045-2322

e-ISSN

—

Svazek periodika

9

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

"Article Number: 16700"

Kód UT WoS článku

000496129600049

EID výsledku v databázi Scopus

2-s2.0-85074961050