Cyclosporine A inhibits MRTF‐SRF signaling through Na+/K+ ATPase inhibition and actin remodeling.

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F19%3A73598705" target="_blank" >RIV/61989592:15310/19:73598705 - isvavai.cz</a>

Result on the web

<a href="https://onlinelibrary.wiley.com/doi/full/10.1096/fba.2019-00027" target="_blank" >https://onlinelibrary.wiley.com/doi/full/10.1096/fba.2019-00027</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1096/fba.2019-00027" target="_blank" >10.1096/fba.2019-00027</a>

Result language

angličtina

Original language name

Cyclosporine A inhibits MRTF‐SRF signaling through Na+/K+ ATPase inhibition and actin remodeling.

Original language description

Calcineurin inhibitors (CNI) are the pillars of immunosuppression in transplantation. However, they display a potent nephrotoxicity whose mechanisms remained widely unsolved. We used an untargeted quantitative proteomic approach (iTRAQ technology) to highlight new targets of CNI in renal proximal tubular cells (RPTCs). CNI‐treated RPTCs proteome displayed an over‐representation of actin‐binding proteins with a CNI‐specific expression profile. Cyclosporine A (CsA) induced F‐actin remodeling and depolymerization, decreased F‐actin‐stabilizing, polymerization‐promoting cofilin (CFL) oligomers, and inhibited the G‐actin‐regulated serum response factor (SRF) pathway. Inhibition of CFL canonical phosphorylation pathway reproduced CsA effects; however, S3‐R, an analogue of the phosphorylation site of CFL prevented the effects of CsA which suggests that CsA acted independently from the canonical CFL regulation. CFL is known to be regulated by the Na+/K+‐ATPase. Molecular docking calculations identified two inhibiting sites of CsA on Na+/K+‐ATPase and a 23% decrease in Na+/K+‐ATPase activity of RPTCs was observed with CsA. Ouabain, a specific inhibitor of Na+/K+‐ATPase also reproduced CsA effects on actin organization and SRF activity. Altogether, these results described a new original pathway explaining CsA nephrotoxicity.

Czech name

—

Czech description

—

Type

J_ost - Miscellaneous article in a specialist periodical

CEP classification

—

OECD FORD branch

10610 - Biophysics

Project

<a href="/en/project/LO1204" target="_blank" >LO1204: Sustainable development of research in the Centre of the Region Haná</a><br>

Continuities

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

Publication year

2019

Confidentiality

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

Name of the periodical

FASEB BioAdvances

ISSN

2573-9832

e-ISSN

—

Volume of the periodical

1

Issue of the periodical within the volume

9

Country of publishing house

US - UNITED STATES

Number of pages

18

Pages from-to

561-578

UT code for WoS article

—

EID of the result in the Scopus database

—