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

0518381 - ÚFE 2020 RIV GB eng J - Článek v odborném periodiku
Hemmerová, Erika - Špringer, Tomáš - Krištofiková, Z. - Homola, Jiří
In vitro study of interaction of 17 beta-hydroxysteroid dehydrogenase type 10 and cyclophilin D and its potential implications for Alzheimer's disease.
Scientific Reports. -, č. 9 (2019), č. článku 16700. ISSN 2045-2322. E-ISSN 2045-2322
Grant CEP: GA MZd(CZ) NV16-27611A
Institucionální podpora: RVO:67985882
Klíčová slova: Surface-plasmon resonance * A beta * Mitochondrial dysfunction
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 3.998, rok: 2019
Způsob publikování: Open access
https://www.nature.com/articles/s41598-019-53157-7

In early stages of Alzheimer's disease (AD), amyloid-beta (A beta) accumulates in neuronal mitochondria where it interacts with a number of biomolecules including 17beta-hydroxysteroide dehydrogenase 10 (17 beta-HSD10) and cyclophilin D (cypD). It has been hypothesized that 17 beta-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 A beta. In this work, we demonstrate for the first time that 17 beta-HSD10 and cypD form a stable complex in vitro. Furthermore, we show that factors, such as pH, ionic environment and the presence of A beta, affect the ability of 17 beta-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 A beta (A beta(1-40) and A beta(1-42)) affect the interaction between 17 beta-HSD10 and cypD differently and that A beta(1-42) (in contrast to A beta(1-40)) is capable of simultaneously binding both 17 beta-HSD10 and cypD in a tricomplex.
Trvalý link: http://hdl.handle.net/11104/0303532