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Prominent role of DPP III in the E2-mediated protection against hyperoxia in liver of female CBA/H mice

Sobočanec, Sandra; Filić, Vedrana; Matovina, Mihaela; Majhen, Dragomira; Mačak Šafranko, Željka; Popović Hadžija, Marijana; Krsnik, Željka; Gudan Kurilj, Andrea; Šarić, Ana; Abramić, Marija; Balog, Tihomir (2016) Prominent role of DPP III in the E2-mediated protection against hyperoxia in liver of female CBA/H mice. Redox Biology, 8 . pp. 149-159. ISSN 2213-2317

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A number of age-related diseases have a low incidence in females, which is attributed to a protective effect of sex hormones. For instance, the female sex hormone estrogen (E2) has a well established cytoprotective effect against oxidative stress, which strongly contributes to ageing. However, the mechanism by which E2 exerts its protective activity remains elusive. In this study we address the question whether the E2-induced protective effect against hyperoxia is mediated by the Nrf-2/Keap-1 signaling pathway. In particular, we investigate the E2-induced expression and cellular distribution of DPP III monozinc exopeptidase, a member of the Nrf-2/Keap-1 pathway, upon hyperoxia treatment. We find that DPP III accumulates in the nucleus in response to hyperoxia. Further, we show that combined induction of hyperoxia and E2 administration have an additive effect on the nuclear accumulation of DPP III. The level of nuclear accumulation of DPP III is comparable to nuclear accumulation of Nrf-2 in healthy female mice exposed to hyperoxia. In ovariectomized females exposed to hyperoxia, supplementation of E2 induced upregulation of DPP III, Ho-1, Sirt-1 and downregulation of Ppar-γ. While other cytoprotective mechanisms cannot be excluded, these findings demonstrate a prominent role of DPP III, along with Sirt-1, in the E2-mediated protection against hyperoxia

Item Type: Article
Additional Information: The authors would like to thank Iva Pesun Medimorec for her excellent technical contribution in performing surgical procedures of ovariectomy and Ana Jagust for her excellent technical assistance in performing immunohistochemical analyses. The authors want to thank Dr. Anita Krisko and Dr. Igor Weber for critical evaluation of the Manuscript. This research is funded by Croatian Ministry of Science, Education and Sports, Grant nos. 098-0982464-1647, 098-1191344-2938, IBRO 2013 RHP and FP7-REGPOT-2012-2013-1, Grant agreement number 316289 - InnoMol.
Uncontrolled Keywords:
Subjects: NATURAL SCIENCES > Biology > Biochemistry and Molecular Biology
BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences > Human Genetics, Genomics and Proteomics
Divisions: Division of Molecular Biology
Division of Molecular Medicine
Project titleProject leaderProject codeProject type
Sirtuin3 kao posrednik mitohondrijske funkcije u estrogen-ovisnoj otpornosti na oksidativni stres i prehranu s visokim udjelom masti-SuMERATihomir BalogIP-2014-09-4533HRZZ
Molekularna enzimologija i proteinske interakcije hidrolaza-Marija Abramić098-1191344-2938MZOS
Enhancement of the Innovation Potential in SEE through new Molecular Solutions in Research and Development-INNOMOLUNSPECIFIED316289EK
Depositing User: Tihomir Balog
Date Deposited: 06 Dec 2017 11:58
DOI: 10.1016/j.redox.2016.01.003

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