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dc.creatorPetrović, Anja
dc.creatorBogojević, Desanka
dc.creatorJovanović Stojanov, Sofija
dc.creatorMartinović, Vesna
dc.creatorIvanović Matić, Svetlana
dc.creatorPoznanović, Goran
dc.creatorGrigorov, Ilijana
dc.creatorKorać, Aleksandra
dc.creatorGolić, Igor
dc.creatorStevanović, Jelena
dc.date.accessioned2017-11-23T07:57:03Z
dc.date.available2018-07-10
dc.date.issued2017
dc.identifier.urihttp://link.springer.com/10.1007/s13105-017-0574-0
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/pubmed/28695466
dc.identifier.urihttp://ibiss-r.rcub.bg.ac.rs/123456789/2787
dc.description.abstractThe progression of oxidative stress, resulting cell damage, and cell death underlies the etiology of liver damage/dysfunction as a complication of diabetes. High-mobility group box 1 (HMGB1) protein, a chromatin-binding nuclear protein and damage-associated molecular pattern molecule, is integral to oxidative stress and signaling pathways regulating cell death and cell survival. We previously found that in streptozotocin (STZ)-induced diabetic rats, reduction of oxidative stress after melatonin administration lowered necrotic cell death and increased expression of HMGB1 and hepatocellular damage. In the present study, we examined whether alleviation of diabetes-attendant oxidative stress and ensuing change in HMGB1 expression influence the dynamic equilibrium between apoptosis/autophagy and liver damage. We observed that elevated HMGB1 protein levels in diabetic rat liver accompanied increased interactions of HMGB1 with TLR4 and RAGE, and activation of the intrinsic apoptotic pathway and Beclin 1-dependent autophagy. The absence of p62 degradation in diabetic rat liver pointed to defective autophagy which was responsible for lower autophagosome/autophagolysosome formation and an increased apoptosis/autophagy ratio. Compared to diabetic rats, in melatonin-treated diabetic rats, the structure of liver cells was preserved, HMGB1/TLR4 interaction and downstream apoptotic signaling were significantly reduced, HMGB1/Beclin 1 colocalization and interactions were augmented and Beclin 1-mediated autophagy, mithophagy in particular, were increased. We concluded that in mild oxidative stress, HMGB1 is cytoprotective, whereas in intense oxidative stress, HMGB1 actions promote cell death and liver damage. Since reduced HMGB1 binds to RAGE but not to TLR4, redox modification of HMGB1 as a mechanism regulating the cross-talk between apoptosis and autophagy in diabetes is discussed.
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173020/RS//
dc.rightsrestrictedAccess
dc.sourceJournal of Physiology and Biochemistry
dc.subjectApoptosis/autophagy interplay
dc.subjectDiabetes
dc.subjectHMGB1
dc.subjectLiver damage
dc.subjectMelatonin
dc.subjectOxidative stress
dc.titleOxidative stress-dependent contribution of HMGB1 to the interplay between apoptosis and autophagy in diabetic rat liver.
dc.typearticle
dcterms.abstractБогојевић, Десанка; Григоров, Илијана; Јовановић Стојанов, Софија; Мартиновић, Весна; Петровић, Ања; Познановић, Горан; Ивановић Матић, Светлана; Кораћ, Александра; Голић, Игор; Стевановић, Јелена
dc.rights.holder© University of Navarra 2017
dc.description.noteThis is a post-peer-review, pre-copyedit version of an article published in Journal of Physiology and Biochemistry. The final authenticated version is available online at: [http://dx.doi.org/10.1007/s13105-017-0574-0]
dc.identifier.doi10.1007/s13105-017-0574-0
dc.identifier.pmid28695466
dc.identifier.scopus2-s2.0-85022184732
dc.identifier.wos000413631200003
dc.citation.apaPetrović, A., Bogojević, D., Korać, A., Golić, I., Jovanović-Stojanov, S., Martinović, V., Ivanović-Matić, S., et al. (2017). Oxidative stress-dependent contribution of HMGB1 to the interplay between apoptosis and autophagy in diabetic rat liver. Journal of Physiology and Biochemistry, DOI:10.1007/s13105-017-0574-0.
dc.citation.vancouverPetrović A, Bogojević D, Korać A, Golić I, Jovanović-Stojanov S, Martinović V, Ivanović-Matić S, Stevanović J, Poznanović G, Grigorov I. Oxidative stress-dependent contribution of HMGB1 to the interplay between apoptosis and autophagy in diabetic rat liver. J Physiol Biochem. 2017;DOI:10.1007/s13105-017-0574-0.
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dc.citation.rankm22


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