The effect of 17β-estradiol on the expression of dipeptidyl peptidase III and heme oxygenase 1 in liver of CBA/H mice

Šafranko, Željka Mačak; Sobočanec, Sandra; Šarić, Ana; Jajčanin-Jozić, Nina; Krsnik, Željka; Aralica, Gorana; Balog, Tihomir; Abramić, Marija

doi:10.1007/s40618-014-0217-z

Cited by 11 publications

(11 citation statements)

References 40 publications

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“…Therefore, although nuclear localization signal of mouse DPP III cannot be predicted with high score, having in mind oxidation prone cysteinyl SH-groups in rodent DPP III and unconventional pattern of redox-sensitive NLSs [32] , we may consider the possibility that nuclear translocation of mouse DPP III could be regulated by the oxidation state of its cysteine residues. We have recently demonstrated that E 2 depletion in normoxic, physiological conditions caused the increase of endogenous oxidative stress, which can be abolished with E 2 administration [22] . Also, lower oxidative stress in E 2 -treated mice was in correlation with increased DPP III protein level, and upregulated Ho-1 gene and protein [22] .…”

Section: Discussionmentioning

confidence: 99%

“…We have recently demonstrated that E 2 depletion in normoxic, physiological conditions caused the increase of endogenous oxidative stress, which can be abolished with E 2 administration [22] . Also, lower oxidative stress in E 2 -treated mice was in correlation with increased DPP III protein level, and upregulated Ho-1 gene and protein [22] . Moreover, it was reported earlier that significantly lower amount of DPP III protein was found in highly oxygenated rat tissue [9] .…”

Section: Discussionmentioning

confidence: 99%

“…Total RNA was extracted from individual mouse liver ( n =3 per each group) using TRIzol reagent (Invitrogen, Carlsbad, CA, USA) according to the manufacturer's instructions. To quantify relative gene expression of dpp III, sirt-1, ppar-γ and ho-1, reverse transcription and real-time PCR analysis were done as described previously [22] . Data were analyzed using the 2 −ΔΔCt method and presented as the fold-change in dpp III, sirt-1, ppar-γ and ho-1 gene expression normalized to endogenous reference gene (β-actin) and relative to the untreated control.…”

Section: Methodsmentioning

confidence: 99%

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Prominent role of exopeptidase DPP III in estrogen-mediated protection against hyperoxia in vivo

et al. 2016

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Prominent role of exopeptidase DPP III in estrogen-mediated protection against hyperoxia in vivo

et al. 2016

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“…However, there are reports showing its association with membranes, and most recently its nuclear localization was observed as well. [10] Extensive investigations of the biochemical properties, structure and dynamics of this protein have been conducted by our group. [11][12][13][14][15][16] An enhanced level of human DPP III activity and protein was found in endometrial carcinomas and in ovarian malignant neoplasms.…”

Section: Introductionmentioning

confidence: 99%

Human DPP III – Keap1 Interactions: A Combined Experimental And Computational Study

Gundić¹,

Tomić²,

Wade³

et al. 2016

Croat. Chem. Acta

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Kelch-like ECH associated protein 1 (Keap1) is a cellular sensor for oxidative stress and a negative regulator of the transcription factor Nrf2. Keap1 and Nrf2 control expression of nearly 500 genes with diverse cytoprotective functions and the Nrf2-Keap1 signaling pathway is a major regulator of cytoprotective responses to oxidative and electrophilic stress. It was found that the metallopeptidase dipeptidyl peptidase III (DPP III) contributes to Nrf2 activation by binding to Keap1, probably by binding to the Kelch domain, and thereby influences Nrf2 activity in cancer. We here first determined that the KD of the DPP III-Kelch domain complex is in the submicromolar range. In order to elucidate the molecular details of the DPP III -Kelch interaction we then built models of the complex between human DPP III and the Keap1 Kelch domain and performed coarse-grained and atomistic simulations of the complexes. In the most stable complexes, the ETGE motif in the DPP III flexible loop binds near the central pore of the six-blade β-propeller Kelch domain. According to the preliminary HD exchange experiments DPP III binds to the more unstructured end of Kelch domain. According to the results of MD simulations DPP III binding to the Kelch domain does not influence the overall DPP III structure or the long-range domain fluctuations. We can conclude that DPP III forms the stable complexes with the Keap1 Kelch domain by inserting the flexible loop into the entrance to the central pore of the six blade β-propeller Kelch domain at its more unstructured, N-terminus.

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“…Studies using female animals have shown that 17-β-estradiol (E 2 ) can act as a mediator of higher glucose consumption [ 14 , 15 ]. In our previous studies we showed female-biased resistance to oxidative stress in young adult mice [ 16 ] that was in relationship with protective effect of E 2 [ 17 ]. Since most metabolic studies have been conducted in only one sex, little attention has been paid to understanding the sex specificity of the above mentioned molecular pathways [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Diminished Resistance to Hyperoxia in Brains of Reproductively Senescent Female CBA/H Mice

Šarić

Sobočanec

Šafranko

et al. 2015

Med Sci Monit Basic Res

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BackgroundWe have explored sex differences in ability to maintain redox balance during acute oxidative stress in brains of mice. We aimed to determine if there were differences in oxidative/antioxidative status upon hyperoxia in brains of reproductively senescent CBA/H mice in order to elucidate some of the possible mechanisms of lifespan regulation.Material/MethodsThe brains of 12-month-old male and female CBA/H mice (n=9 per sex and treatment) subjected to 18-h hyperoxia were evaluated for lipid peroxidation (LPO), antioxidative enzyme expression and activity - superoxide dismutase 1 and 2 (Sod-1, Sod-2), catalase (Cat), glutathione peroxidase 1 (Gpx-1), heme-oxygenase 1 (Ho-1), nad NF-E2-related factor 2 (Nrf2), and for 2-deoxy-2-[18F] fluoro-D-glucose (18FDG) uptake.ResultsNo increase in LPO was observed after hyperoxia, regardless of sex. Expression of Nrf-2 showed significant downregulation in hyperoxia-treated males (p=0.001), and upregulation in hyperoxia-treated females (p=0.023). Also, in females hyperoxia upregulated Sod-1 (p=0.046), and Ho-1 (p=0.014) genes. SOD1 protein was upregulated in both sexes after hyperoxia (p=0.009 for males and p=0.011 for females). SOD2 protein was upregulated only in females (p=0.008) while CAT (p=0.026) and HO-1 (p=0.042) proteins were increased after hyperoxia only in males. Uptake of 18FDG was decreased after hyperoxia in the back brain of females.ConclusionsWe found that females at their reproductive senescence are more susceptible to hyperoxia, compared to males. We propose this model of hyperoxia as a useful tool to assess sex differences in adaptive response to acute stress conditions, which may be partially responsible for observed sex differences in longevity of CBA/H mice.

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The effect of 17β-estradiol on the expression of dipeptidyl peptidase III and heme oxygenase 1 in liver of CBA/H mice

Cited by 11 publications

References 40 publications

Prominent role of exopeptidase DPP III in estrogen-mediated protection against hyperoxia in vivo

Prominent role of exopeptidase DPP III in estrogen-mediated protection against hyperoxia in vivo

Human DPP III – Keap1 Interactions: A Combined Experimental And Computational Study

Diminished Resistance to Hyperoxia in Brains of Reproductively Senescent Female CBA/H Mice

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