dc.contributor.author |
Szobi A |
|
dc.contributor.author |
Goncalvesova E |
|
dc.contributor.author |
Varga, Zoltán |
|
dc.contributor.author |
Leszek P |
|
dc.contributor.author |
Kusmierczyk M |
|
dc.contributor.author |
Hulman M |
|
dc.contributor.author |
Kyselovic J |
|
dc.contributor.author |
Ferdinandy, Péter |
|
dc.contributor.author |
Adameova A |
|
dc.date.accessioned |
2018-08-30T08:20:17Z |
|
dc.date.available |
2018-08-30T08:20:17Z |
|
dc.date.issued |
2017 |
|
dc.identifier |
85018418608 |
|
dc.identifier.citation |
pagination=86, pages: 7;
journalVolume=15;
journalIssueNumber=1;
journalTitle=JOURNAL OF TRANSLATIONAL MEDICINE; |
|
dc.identifier.uri |
http://repo.lib.semmelweis.hu//handle/123456789/6190 |
|
dc.identifier.uri |
doi:10.1186/s12967-017-1189-5 |
|
dc.description.abstract |
BACKGROUND: Cell loss and subsequent deterioration of contractile function are hallmarks of chronic heart failure (HF). While apoptosis has been investigated as a participant in the progression of HF, it is unlikely that it accounts for the total amount of non-functional tissue. In addition, there is evidence for the presence of necrotic cardiomyocytes in HF. Therefore, the objective of this study was to investigate the necroptotic proteins regulating necroptosis, a form of programmed necrosis, and thereby assess its potential role in human end-stage HF. METHODS: Left ventricular samples of healthy controls (C) and patients with end-stage HF due to myocardial infarction (CAD) or dilated cardiomyopathy (DCM) were studied. Immunoblotting for necroptotic and apoptotic markers was performed. Triton X-114 fractionated samples were analyzed to study differences in subcellular localization. RESULTS: Elevated expression of RIP1 (receptor-interacting protein), pSer227-RIP3 and its total levels were observed in HF groups compared to controls. On the other hand, caspase-8 expression, a proapoptotic protease negatively regulating necroptosis, was downregulated suggesting activation of necroptosis signaling. Total mixed-lineage kinase domain-like protein (MLKL) expression did not differ among the groups; however, active cytotoxic forms of MLKL were present in all HF samples while they were expressed at almost undetectable levels in controls. Interestingly, pThr357-MLKL unlike pSer358-MLKL, was higher in DCM than CAD. In HF, the subcellular localization of both RIP3 and pThr357-MLKL was consistent with activation of necroptosis signaling. Expression of main apoptotic markers has not indicated importance of apoptosis. CONCLUSIONS: This is the first evidence showing that human HF of CAD or DCM etiology is positive for markers of necroptosis which may be involved in the development of HF. |
|
dc.relation.ispartof |
urn:issn:1479-5876 |
|
dc.title |
Analysis of necroptotic proteins in failing human hearts |
|
dc.type |
Journal Article |
|
dc.date.updated |
2018-08-27T18:04:19Z |
|
dc.language.rfc3066 |
en |
|
dc.identifier.mtmt |
3218308 |
|
dc.identifier.wos |
000400612700002 |
|
dc.identifier.pubmed |
28454582 |
|
dc.contributor.department |
SE/AOK/I/Farmakológiai és Farmakoterápiás Intézet |
|
dc.contributor.institution |
Semmelweis Egyetem |
|