Silencing HMGB1 expression inhibits adriamycin's heart toxicity via TLR4 dependent manner through MAPK signal transduction

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dc.authoridSariman, Melda/0000-0003-0898-529X
dc.authoridKAYA, Salih Tunc/0000-0002-4133-407X
dc.authoridSevgiler, Yusuf/0000-0002-4373-2389
dc.contributor.authorTaskin, Eylem
dc.contributor.authorGuven, Celal
dc.contributor.authorKaya, Salih Tunc
dc.contributor.authorSariman, Melda
dc.contributor.authorEmrence, Zeliha
dc.contributor.authorEkmekci, Sema Sirma
dc.contributor.authorAbaci, Neslihan
dc.date.accessioned2024-11-07T13:34:40Z
dc.date.available2024-11-07T13:34:40Z
dc.date.issued2020
dc.departmentNiğde Ömer Halisdemir Üniversitesi
dc.description.abstractPurpose: Adriamycin (APR) is a commonly used anti-cancer drug. ADR has toxic effects on cardiomyocytes and leads to heart failure. However, the underlying mechanism(s) by which ADR causes heart failure is still not clarified exactly. The aim of present study is to investigate whether ADR-induced heart failure is mediated via HMGB1/TLR4 to initiate the apoptosis through MAPK/AMPK pathways. Methods: H9c2 cell line was used to create four groups as a control, HMGB1 inhibition, ADR, ADR+HMGB1 inhibition. Silencing HMGB1 was performed with specific small interfering RNA. ADR was used at 2 mu M concentration for 36 and 48 hours. Protein and genes expressions, apoptosis was measured. Results: Although ADR decreased AMPK, pAMPK, ERK1/2, pERK1/2, p38, JNK protein expression, ADR+HMGB1 inhibition led to change those protein expressions. The effect of silencing of HMGB1 prevented apoptosis induced by ADR in the cells. HMGB1 caused changes a kind of posttranscriptional modification on the TLR4 receptor. This posttranscriptional modification of TLR4 receptor led to decreased AMPK protein level, but phosphorylated-AMPK. This alternation of AMPK protein caused enhancing of JNK protein, resulting from the decline of p38 and ERK protein levels. Eventually, JNK triggered apoptosis by a caspase-dependent pathway. The number of TUNEL positive and active caspase 8 cells at ADR was high, although HMGB1 silencing could decrease the cell numbers. Conclusions: Inhibition of HMGB1 might prevent the lose of the cardiac cell by inhibition of apoptotic pathway, therefore HMGB1 plays an essential role as amplifying on ADR toxicity on the heart by TLR4.
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) [114S118]
dc.description.sponsorshipThis study was supported by The Scientific and Technological Research Council of Turkey (TUBITAK) as a Project No: 114S118.
dc.identifier.endpage565
dc.identifier.issn1107-0625
dc.identifier.issn2241-6293
dc.identifier.issue1
dc.identifier.pmid32277683
dc.identifier.scopus2-s2.0-85081558392
dc.identifier.scopusqualityQ3
dc.identifier.startpage554
dc.identifier.urihttps://hdl.handle.net/11480/16112
dc.identifier.volume25
dc.identifier.wosWOS:000517089300076
dc.identifier.wosqualityQ4
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherImprimatur Publications
dc.relation.ispartofJournal of Buon
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_20241106
dc.subjectadriamycin
dc.subjectHMGB1
dc.subjectAMPK
dc.subjectTLR4
dc.subjectapoptosis
dc.subjectcardiac muscle cell
dc.titleSilencing HMGB1 expression inhibits adriamycin's heart toxicity via TLR4 dependent manner through MAPK signal transduction
dc.typeArticle

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