dc.contributor.author
Winter, Julia
dc.contributor.author
Hammer, Elke
dc.contributor.author
Heger, Jacqueline
dc.contributor.author
Schultheiss, Heinz-Peter
dc.contributor.author
Rauch, Ursula
dc.contributor.author
Landmesser, Ulf
dc.contributor.author
Dörner, Andrea
dc.date.accessioned
2020-01-22T10:25:45Z
dc.date.available
2020-01-22T10:25:45Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/26490
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-26251
dc.description.abstract
The cardiac-specific overexpression of the adenine nucleotide translocase 1 (ANT1) has cardioprotective effects in various experimental heart disease models. Here, we analyzed the link between ANT1 expression and heat shock protein 27 (HSP27)-mediated toll-like receptor 4 (TLR4) signaling, which represents a novel communication pathway between mitochondria and the extracellular environment. The interaction between ANT1 and HSP27 was identified by co-immunoprecipitation from neonatal rat cardiomyocytes. ANT1 transgenic (ANT1-TG) cardiomyocytes demonstrated elevated HSP27 expression levels. Increased levels of HSP27 were released from the ANT1-TG cardiomyocytes under both normoxic and hypoxic conditions. Extracellular HSP27 stimulated TLR4 signaling via protein kinase B (AKT). The HSP27-mediated activation of the TLR4 pathway was more pronounced in ANT1-TG cardiomyocytes than in wild-type (WT) cardiomyocytes. HSP27-specific antibodies inhibited TLR4 activation and the expression of HSP27. Inhibition of the HSP27-mediated TLR4 signaling pathway with the TLR4 inhibitor oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) reduced the mitochondrial membrane potential (∆ψm) and increased caspase 3/7 activity, which are both markers for cell stress. Conversely, treating cardiomyocytes with recombinant HSP27 protein stimulated TLR4 signaling, induced HSP27 and ANT1 expression, and stabilized the mitochondrial membrane potential. The activation of HSP27 signaling was verified in ischemic ANT1-TG heart tissue, where it correlated with ANT1 expression and the tightness of the inner mitochondrial membrane. Our study shows a new mechanism by which ANT1 is part of the cardioprotective HSP27-mediated TLR4 signaling.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
adenine nucleotide translocase 1
en
dc.subject
heat shock protein 27
en
dc.subject
toll-like receptor 4
en
dc.subject
mitochondria
en
dc.subject
cell signaling
en
dc.subject
cardioprotection
en
dc.subject
myocardial infarction
de
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Adenine Nucleotide Translocase 1 Expression is Coupled to the HSP27-Mediated TLR4 Signaling in Cardiomyocytes
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
1588
dcterms.bibliographicCitation.doi
10.3390/cells8121588
dcterms.bibliographicCitation.journaltitle
Cells
dcterms.bibliographicCitation.number
12
dcterms.bibliographicCitation.originalpublishername
MDPI AG
dcterms.bibliographicCitation.volume
8
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
31817787
dcterms.isPartOf.eissn
2073-4409