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  • 1
    Online Resource
    Online Resource
    Biopotential of Underutilized Rosaceae Inflorescences: LC-DAD-MS Phytochemical Profiles Associated with Antioxidant, Antidiabetic, Anti-Inflammatory and Antiproliferative Activity In Vitro
    MDPI AG ; 2022
    In:  Plants Vol. 11, No. 3 ( 2022-01-20), p. 271-
    Details
    In: Plants, MDPI AG, Vol. 11, No. 3 ( 2022-01-20), p. 271-
    Abstract: The aim of this work was to assess the biopotential of the young inflorescence tissues of Prunus, Malus and Chaenomeles in order to evaluate the possibility of their application in the food industry, and to provide a polyphenolic fingerprint for their quality control. The contents of different bioactive compounds and their antioxidant capacities were spectrophotometrically measured, the main phenolic compounds were identified and quantified using LC-DAD-MS, the antidiabetic potential was determined using α-amylase and α-glucosidase inhibition assays, the anti-inflammatory potential was determined using a 5-lipoxygenase inhibition assay, and the cytotoxicity was determined by MTT assay. Using one-way ANOVA, principal component analysis, hierarchical clustering and Pearson’s correlation coefficient, the relations between the samples, and between the samples and the measured parameters, were revealed. In total, 77 compounds were identified. The concentration of sugars was low in M. purpurea, at 1.56 ± 0.08 mg/g DW. The most effective sample in the inhibition of antidiabetic enzymes and anti-inflammatory 5-lipoxygenase was C. japonica. The inhibition of α-glucosidase was strongly positively correlated with the total and condensed tannins, procyanidin dimers and procyanidin tetramer, and was very strongly correlated with chlorogenic acid. In α-amylase inhibition, C. japonica and P. serrulata ‘Kiku Shidare Zakura’ were equally efficient to the standard inhibitor, maltose. The most effective in the growth and proliferation inhibition of HepG2, HCT116 and HaCaT cells was P. avium. The results suggest Prunus, Malus and Chaenomeles inflorescences as functional food ingredients.
    Type of Medium: Online Resource
    ISSN: 2223-7747
    URL: Article
    DOI: 10.3390/plants11030271
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2704341-1
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  • 2
    Online Resource
    Online Resource
    Para-N-Methylpyridinium Pyrenes: Impact of Positive Charge on ds-DNA/RNA and Protein Recognition, Photo-Induced Bioactivity, and Intracellular Localisation
    MDPI AG ; 2022
    In:  Pharmaceutics Vol. 14, No. 11 ( 2022-11-17), p. 2499-
    Details
    In: Pharmaceutics, MDPI AG, Vol. 14, No. 11 ( 2022-11-17), p. 2499-
    Abstract: The 2- and 2,7- substituted para-N-methylpyridinium pyrene cations show high-affinity intercalation into ds-DNAs, whereas their non-methylated analogues interacted with ds-DNA/RNA only in the protonated form (at pH 5), but not at physiological conditions (pH 7). The fluorescence from non-methylated analogues was strongly dependent on the protonation of the pyridines; consequently, they act as fluorescence ratiometric probes for simultaneous detection of both ds-DNA and BSA at pH 5, relying on the ratio between intensities at 420 nm (BSA specific) and 520 nm (DNA specific), whereby exclusively ds-DNA sensing could be switched-off by adjustment to pH 7. Only methylated, permanently charged pyrenes show photoinduced cleavage of circular DNA, attributed to pyrene-mediated irradiation-induced production of singlet oxygen. Consequently, the moderate toxicity of these cations against human cell lines is strongly increased upon irradiation. Detailed studies revealed increased total ROS production in cells treated by the compounds studied, accompanied by cell swelling and augmentation of cellular complexity. The most photo-active 2-para-N-methylpyridinium pyrene showed significant localization at mitochondria, its photo-bioactivity likely due to mitochondrial DNA damage. Other derivatives were mostly non-selectively distributed between various cytoplasmic organelles, thus being less photoactive.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    URL: Article
    DOI: 10.3390/pharmaceutics14112499
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
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  • 3
    Online Resource
    Online Resource
    Chronic High Fat Diet Intake Impairs Hepatic Metabolic Parameters in Ovariectomized Sirt3 KO Mice
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 8 ( 2021-04-20), p. 4277-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 8 ( 2021-04-20), p. 4277-
    Abstract: High fat diet (HFD) is an important factor in the development of metabolic diseases, with liver as metabolic center being highly exposed to its influence. However, the effect of HFD-induced metabolic stress with respect to ovary hormone depletion and sirtuin 3 (Sirt3) is not clear. Here we investigated the effect of Sirt3 in liver of ovariectomized and sham female mice upon 10 weeks of feeding with standard-fat diet (SFD) or HFD. Liver was examined by Folch, gas chromatography and lipid hydroperoxide analysis, histology and oil red staining, RT-PCR, Western blot, antioxidative enzyme and oxygen consumption analyses. In SFD-fed WT mice, ovariectomy increased Sirt3 and fatty acids synthesis, maintained mitochondrial function, and decreased levels of lipid hydroperoxides. Combination of ovariectomy and Sirt3 depletion reduced pparα, Scd-1 ratio, MUFA proportions, CII-driven respiration, and increased lipid damage. HFD compromised CII-driven respiration and activated peroxisomal ROS scavenging enzyme catalase in sham mice, whereas in combination with ovariectomy and Sirt3 depletion, increased body weight gain, expression of NAFLD- and oxidative stress-inducing genes, and impaired response of antioxidative system. Overall, this study provides evidence that protection against harmful effects of HFD in female mice is attributed to the combined effect of female sex hormones and Sirt3, thus contributing to preclinical research on possible sex-related therapeutic agents for metabolic syndrome and associated diseases.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22084277
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Identification of SH2 Domain-Containing Protein 3C as a Novel, Putative Interactor of Dipeptidyl Peptidase 3
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 18 ( 2023-09-16), p. 14178-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 18 ( 2023-09-16), p. 14178-
    Abstract: Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent exopeptidase with broad specificity for four to eight amino acid residue substrates. It has a role in the regulation of oxidative stress response NRF2–KEAP1 pathway through the interaction with KEAP1. We have conducted stable isotope labeling by amino acids in a cell culture coupled to mass spectrometry (SILAC-MS) interactome analysis of TRex HEK293T cells using DPP3 as bait and identified SH2 Domain-Containing Protein 3C (SH2D3C) as prey. SH2D3C is one of three members of a family of proteins that contain both the SH2 domain and a domain similar to guanine nucleotide exchange factor domains of Ras family GTPases (Ras GEF-like domain), named novel SH2-containing proteins (NSP). NSPs, including SH2D3C (NSP3), are adaptor proteins involved in the regulation of adhesion, migration, tissue organization, and immune response. We have shown that SH2D3C binds to DPP3 through its C-terminal Ras GEF-like domain, detected the colocalization of the proteins in living cells, and confirmed direct interaction in the cytosol and membrane ruffles. Computational analysis also confirmed the binding of the C-terminal domain of SH2D3C to DPP3, but the exact model could not be discerned. This is the first indication that DPP3 and SH2D3C are interacting partners, and further studies to elucidate the physiological significance of this interaction are on the way.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms241814178
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 5
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    Online Resource
    Role of Sirt3 in Differential Sex-Related Responses to a High-Fat Diet in Mice
    MDPI AG ; 2020
    In:  Antioxidants Vol. 9, No. 2 ( 2020-02-20), p. 174-
    Details
    In: Antioxidants, MDPI AG, Vol. 9, No. 2 ( 2020-02-20), p. 174-
    Abstract: Metabolic homeostasis is differently regulated in males and females. Little is known about the mitochondrial Sirtuin 3 (Sirt3) protein in the context of sex-related differences in the development of metabolic dysregulation. To test our hypothesis that the role of Sirt3 in response to a high-fat diet (HFD) is sex-related, we measured metabolic, antioxidative, and mitochondrial parameters in the liver of Sirt3 wild-type (WT) and knockout (KO) mice of both sexes fed with a standard or HFD for ten weeks. We found that the combined effect of Sirt3 and an HFD was evident in more parameters in males (lipid content, glucose uptake, pparγ, cyp2e1, cyp4a14, Nrf2, MnSOD activity) than in females (protein damage and mitochondrial respiration), pointing towards a higher reliance of males on the effect of Sirt3 against HFD-induced metabolic dysregulation. The male-specific effects of an HFD also include reduced Sirt3 expression in WT and alleviated lipid accumulation and reduced glucose uptake in KO mice. In females, with a generally higher expression of genes involved in lipid homeostasis, either the HFD or Sirt3 depletion compromised mitochondrial respiration and increased protein oxidative damage. This work presents new insights into sex-related differences in the various physiological parameters with respect to nutritive excess and Sirt3.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    URL: Article
    DOI: 10.3390/antiox9020174
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2704216-9
    SSG: 15,3
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  • 6
    Online Resource
    Online Resource
    Sirt3 Exerts Its Tumor-Suppressive Role by Increasing p53 and Attenuating Response to Estrogen in MCF-7 Cells
    MDPI AG ; 2020
    In:  Antioxidants Vol. 9, No. 4 ( 2020-04-01), p. 294-
    Details
    In: Antioxidants, MDPI AG, Vol. 9, No. 4 ( 2020-04-01), p. 294-
    Abstract: Estrogen (E2) is a major risk factor for the initiation and progression of malignancy in estrogen receptor (ER) positive breast cancers, whereas sirtuin 3 (Sirt3), a major mitochondrial NAD+-dependent deacetylase, has the inhibitory effect on the tumorigenic properties of ER positive MCF-7 breast cancer cells. Since it is unclear if this effect is mediated through the estrogen receptor alpha (ERα) signaling pathway, in this study, we aimed to determine if the tumor-suppressive function of Sirt3 in MCF-7 cells interferes with their response to E2. Although we found that Sirt3 improves the antioxidative response and mitochondrial fitness of the MCF-7 cells, it also increases DNA damage along with p53, AIF, and ERα expression. Moreover, Sirt3 desensitizes cells to the proliferative effect of E2, affects p53 by disruption of the ERα–p53 interaction, and decreases proliferation, colony formation, and migration of the cells. Our observations indicate that these tumor-suppressive effects of Sirt3 could be reversed by E2 treatment only to a limited extent which is not sufficient to recover the tumorigenic properties of the MCF-7 cells. This study provides new and interesting insights with respect to the functional role of Sirt3 in the E2-dependent breast cancers.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    URL: Article
    DOI: 10.3390/antiox9040294
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2704216-9
    SSG: 15,3
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  • 7
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    Online Resource
    High Growing Temperature Changes Nutritional Value of Broccoli (Brassica oleracea L. convar. botrytis (L.) Alef. var. cymosa Duch.) Seedlings
    MDPI AG ; 2023
    In:  Foods Vol. 12, No. 3 ( 2023-01-29), p. 582-
    Details
    In: Foods, MDPI AG, Vol. 12, No. 3 ( 2023-01-29), p. 582-
    Abstract: High temperature (HT) causes physiological and biochemical changes in plants, which may influence their nutritional potential. This study aimed to evaluate the nutritional value of broccoli seedlings grown at HT on the level of phytochemicals, macro- and microelements, antioxidant capacity, and their extracts’ in vitro cytotoxicity. Total phenols, soluble sugars, carotenoids, quercetin, sinapic, ferulic, p-coumaric, and gallic acid were induced by HT. Contrarily, total flavonoids, flavonols, phenolic acids, hydroxycinnamic acids, proteins, glucosinolates, chlorophyll a and b, and porphyrins were reduced. Minerals As, Co, Cr, Hg, K, Na, Ni, Pb, Se, and Sn increased at HT, while Ca, Cd, Cu, Mg, Mn, and P decreased. ABTS, FRAP, and β-carotene bleaching assay showed higher antioxidant potential of seedlings grown at HT, while DPPH showed the opposite. Hepatocellular carcinoma cells were the most sensitive toward broccoli seedling extracts. The significant difference between control and HT-grown broccoli seedling extracts was recorded in mouse embryonal fibroblasts and colorectal carcinoma cells. These results show that the temperature of seedling growth is a critical factor for their nutritional value and the biological effects of their extracts and should definitely be taken into account when growing seedlings for food purposes.
    Type of Medium: Online Resource
    ISSN: 2304-8158
    URL: Article
    DOI: 10.3390/foods12030582
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2704223-6
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  • 8
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    Online Resource
    Interdisciplinary Study of the Effects of Dipeptidyl-Peptidase III Cancer Mutations on the KEAP1-NRF2 Signaling Pathway
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 4 ( 2022-02-11), p. 1994-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 4 ( 2022-02-11), p. 1994-
    Abstract: Dipeptidyl peptidase III (DPP III) is associated with cancer progression via interaction with KEAP1, leading to upregulation of the KEAP1-NRF2 oxidative stress pathway. Numerous DPP III mutations have been found in human tumor genomes, and it is suggested that some of them may alter affinity for KEAP1. One such example is the DPP III-R623W variant, which in our previous study showed much higher affinity for the Kelch domain of KEAP1 than the wild-type protein. In this work, we have investigated the effects of this mutation in cultured cells and the effects of several other DPP III mutations on the stability of KEAP1-DPP III complex using an interdisciplinary approach combining biochemical, biophysical and molecular biology methods with computational studies. We determined the affinity of the DPP III variants for the Kelch domain experimentally and by molecular modeling, as well as the effects of the R623W on the expression of several NRF2-controlled genes. We confirmed that the R623W variant upregulates NQO1 expression at the transcriptional level. This supports the hypothesis from our previous study that the increased affinity of the R623W variant for KEAP1 leads to upregulation of the KEAP1-NRF2 pathway. These results provide a new perspective on the involvement of DPP III in cancer progression and prognosis.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23041994
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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