Person: ZIK, BERRİN
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ZIK
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BERRİN
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Publication The effect of capsaicin on IGF-I and IGF-IR expression in ovarian granulosa cells(Hellenic Veterinary Medical Soc, 2020-01-01) Güler, Sabire; Zik, Berrin; Güler, Sabire; ZIK, BERRİN; Veteriner Fakültesi; Histoloji ve Embriyoloji Ana Bilim Dalı; AAH-9810-2021; HTY-9355-2023Capsaicin (trans-8-methyl-N-vanillyl-6-noneadamide) is a pungent ingredient in red peppers from the Capsicum family. Insulin-like growth factor-I (IGF-I) is expressed in granulosa cells and has an important role in ovarian development. However, there are no data about the IGF-I expression in ovarian granulosa cells after capsaicin treatment. The aim of this study was to investigate the expression of IGF-I and its receptor (insulin-like growth factor-I receptor [IGF-IR]) in primary rat ovarian granulosa cells after low and high doses of capsaicin treatment. For this, granulosa cells were isolated and cultured from ovaries of 30-day-old female Sprague-Dawley rats. Granulosa cell plates were divided into four groups as cell control (C), vehicle control (V), and 50 mu M and 150 mu M capsaicin groups. In experimental groups, granulosa cells were exposed to capsaicin for 24 hours and immunocytochemistry was performed afterwards using anti-IGF-I and anti-IGF-IR antibodies. Both IGF-I and IGF-IR expressions were found to be significantly increased in parallel to the capsaicin doses. Elevated levels of IGF-I may be a risk factor for ovarian development. Because of the crucial role of IGF-I in ovary development, capsaicin treatment can be effective on follicular development and/or disorders characterized by high IGF-I levels.Publication Upregulation of dual-specificity phosphatase-26 is required for transforming growth factor β1(TGFβ1)-induced Epithelial-mesenchymal transition in A549 and PANC1 cells(Springer, 2022-09-02) Güler, Sabire; Zık, Berrin; Yalçın, Abdullah; GÜLER, SABİRE; ZIK, BERRİN; YALÇIN, ABDULLAH; Veteriner Fakültesi; Biyokimya Ana Bilim Dalı; 0000-0002-7367-6859; 0000-0001-8519-8375; AAH-9810-2021; ABI-4164-2020; AAH-8807-2021; A-5261-2016Background Transforming Growth Factor beta (TGF beta) proteins are potent inducers of the epithelial-mesenchymal transition (EMT) in tumor cells. Although mitogen-activated protein kinase (MAPK) family has been shown to be involved in TGF beta-induced EMT, role of Dual Specificity Phosphatases (DUSP), key regulators of MAPK activity, in TGF beta-induced EMT is largely unkonwn.Methods and results Real-time qPCR analyses were performed to determine the effect of TGF beta 1 on expression of EMT genes and DUSP proteins in the non-small cell lung cancer model A549 and pancreatic adenocarcinoma model PANC1 cells. Western blot analyses were conducted to study the changes in protein levels of EMT proteins and select DUSP proteins, as well as phosphorylations of MAPK proteins upon TGF beta 1 stimulation. Small interfering RNA (siRNA) was utilized to reduce expressions of DUSP genes. We observed that the EMT phenotype coincided with increases in phosphorylations of the MAPK proteins ERK1/2, p38MAPK, and JNK upon TGF beta 1 stimulation. Real-time qPCR analysis showed increases in DUSP15 and DUSP26 mRNA levels and Western blot analysis confirmed the increase in DUSP26 protein levels in both A549 and PANC1 cells treated with TGF beta 1 relative to control. Silencing of DUSP26 expression by siRNA markedly suppressed the effect of TGF beta 1 on E-cadherin and mesenchymal genes in the cells.Conclusions Data provided suggest that TGF beta 1 modulates the expression of DUSP genes and that upregulation of DUSP26 may be required for TGF beta 1-promoted EMT in A549 and PANC1 cells. Further studies should be carried out to elucidate the requirement of individual DUSPs in TGF beta 1-associated EMT in tumor cells.Publication Effect of tamoxifen on ovarian reserve: A randomized controlled assessor-blind trial in a mouse model(Galenos Yayıncılık, 2014-12-01) Akduman, Ayşe Topçu; Özerkan, Kemal; Zık, Berrin; Peker, Sabire; Avcı, Berrin; Ata, Barış; Akduman, Ayşe Topçu; ÖZERKAN, KEMAL; ZIK, BERRİN; Peker, Sabire; AVCI, BERRİN; Ata, Barış; Tıp Fakültesi; Histoloji ve Embriyoloji Ana Bilim Dalı; 0000-0003-1106-3747; CBC-2905-2022; AAH-9791-2021; AAH-9810-2021; FUW-0951-2022; ABE-6685-2020; C-8049-2013Objective: To determine whether tamoxifen (TMX) exposure causes a permanent decrease in ovarian reserve.Material and Methods: A randomized controlled assessor-blind trial including 30 adult female inbred BALB/C mice. Fifteen mice in the TMX group were given a single 0.1-mg dose of TMX intraperitoneally. Fifteen mice in the control group were given a single dose of the vehicle at the same volume intraperitoneally. Two cycles later, blood samples were collected for determination of anti-Mullerian hormone (AMH) levels, and the mice were sacrificed. After gonadectomy, ovarian size was measured, and follicles were counted under light microscopy.Results: Median serum AMH levels were 6.53 and 6.14 ng/ml in the control and TMX groups, respectively (p=0.03). Ovarian size was significantly decreased in the TMX group. While the number of primordial (9 vs 8), primary (6 vs 3), and secondary (4.5 vs 5) follicles were similar, there were significantly fewer preantral (11.5 vs 6, p<0.01) and antral (2 vs 1, p: 0.03) follicles, as well as corpora lutea (6 vs 3, p: 0.04), in the TMX group than in the control group. The number of atretic (2.5 vs 5, p: 0.048) follicles was increased in the TMX group.Conclusion: Tamoxifen administration leads to arrested growth of gonadotropin-sensitive follicles, while insensitive follicles can remain unaffected. TMX is merely an endocrine disruptor, and it does not cause a decrease in primordial follicle pool.Publication Synergistic effect of feed additives on cell proliferation and morphology in quail (coturnix coturnix japonica) duodenum(Hellenic Veterinary Medical Soc, 2022-07-01) YEŞİLBAĞ, DERYA; Asmaz, Ender Deniz; Yeşilbağ, Derya; Odabası, F.; Zık, Berrin; ZIK, BERRİN; Veteriner Fakültesi; Histoloji ve Embriyoloji Ana Bilim Dalı; AAH-9810-2021; HPG-0648-2023The present study aimed to investigate the effect of a commercial probiotic and a commercial essential oil blend and their mixture, as a natural feed additive, on the expression level of Proliferating Cell Nuclear Antigen (PCNA), proliferation index (PI), and total mucosal thickness of quails. 1-day-old Japanese (Coturnix coturnix Japon-ica) quails, including both males and females, were divided into four groups as follows: (1) control treatment without medication (n: 15); (2) 18 g/ ton-1 probiotic (n: 15); (3) 300 g/ ton-1 essential oil blend (n: 15) and (4) 18 g/ ton-1 probiotic plus 300 g/ ton-1 essential oil blend (n: 15). The study evaluated the effect of natural feed additives added to the quail diet on intestinal health by immunohistochemical and histological analysis. At the end of the experiment, the quail's duodenum was removed, fixed in 10% neutral buffered formalin, and performed a histological examination.As a result of the study, it was determined that the PCNA expressions, proliferation index, and mucosal thickness were generally significantly increased in the experimental groups compared to the control group (P<0.001). The combina-tion of additives caused a synergistic effect for this study. All data were statistically significant in the group where the probiotic and essential oil mixture was used together. It has been determined that these feed additives combination stimulates cell proliferation in the duodenum, where nutrients are absorbed and positively affect intestinal morphology.Publication Overexpression of dual-specificity phosphatases 4 and 13 attenuates transforming growth factor β1-induced migration and drug resistance in A549 cells in vitro(Academic Press Inc Elsevier Science, 2022-03-23) Güler, Sabire; Altunok, Tuğba H.; Sarıoğlu, Aybike; Zik, Berrin; Aşmaz, Deniz; Kayapunar, Nuray; Sönmez, Öner; Tepedelen, Burcu Erbaykent; Yalçın, Abdullah; GÜLER, SABİRE; Altunok, Tuğba H.; Sarıoğlu, Aybike; ZIK, BERRİN; Aşmaz, Deniz; Kayapunar, Nuray; SÖNMEZ, ÖNER; Tepedelen, Burcu Erbaykent; YALÇIN, ABDULLAH; Veteriner Fakültesi; Biyokimya Ana Bilim Dalı; 0000-0002-7367-6859; 0000-0003-1263-3799; 0000-0002-1062-332X; 0000-0001-8519-8375; 0000-0002-8287-6617; 0000-0001-6468-8535; AAH-8807-2021; KMY-2643-2024; S-2474-2018; AAH-9810-2021; HPG-0648-2023; GXM-5514-2022; DTN-7054-2022; AAH-6436-2021; ABI-4164-2020Transforming growth factor-beta (TGF beta) proteins induce an epithelial-mesenchymal transition (EMT) programme that is associated with increased invasive and drug-resistant phenotype of carcinoma cells. In addition to the canonical pathway involving SMAD proteins, the mitogen-activated kinase (MAPK) pathway via extracellular signal-regulated kinases 1/2 (ERK1/2) is also involved in promoting and maintaining a mesenchymal phenotype by tumor cells following TGF beta signal activation. As dual-specificity phosphatases (DUSPs) regulate ERK1/2 activity by dephosphorylation, we aimed to examine DUSPs' expression upon TGF beta stimulation and whether DUSPs play a role in the EMT and related phenotypes promoted by TGF beta 1 in A549 cells. We found that TGF beta 1 stimulation led to marked changes in several DUSP proteins, including significant decreases in DUSP4 and DUSP13 expressions. We then showed that the ectopic co-expression of DUSP4/13 suppresses TGF beta 1-induced ERK1/2 phosphorylation and protein levels of the EMT transcription factors Snail and Slug proteins. We then demonstrated that DUSP4/13 co-expression partially inhibited TGF beta 1-promoted migration, invasion, and chemoresistance in A549 cells. Collectively, this report provides data for the involvement of DUSP4/13 in malignant phenotypes regulated by TGF beta 1 in A549 cells. (C) 2022 Elsevier Inc. All rights reserved.Publication Effect of tamoxifen on the notch signaling pathway in ovarian follicles of mice(Taylor & Francis Ltd, 2019-08-18) ZIK, BERRİN; Güler, Sabire; GÜLER, SABİRE; Asmaz, Ender Deniz; Kurnaz, Hilal; Veteriner Fakültesi; Histoloji ve Embriyoloji Ana Bilim Dalı; 0000-0002-7367-6859; HPG-0648-2023; AAH-9810-2021We investigated the effect of tamoxifen (TAM) treatment on the Notch signaling pathway in mouse ovary. Mice were randomly divided into four groups. Control group A animals were untreated. Control group B animals were treated with the vehicle only. Animals of the 0.5 TAM group received 0.5 mg/day TAM. Animals of the 1.5 TAM group received 1.5 mg/day of TAM. TAM was injected subcutaneously for 5 days. Body weights were measured at the start and end of the experiment. Sections were stained using Crossman's modified trichrome to examine general ovarian structure. Other sections were immunostained to demonstrate Jagged 1, Ki 67 and Notch 2. The TUNEL method was used to detect apoptosis. No significant differences in body weight or ovarian weight were found among the experimental groups. The number of primordial follicles was greater in the treatment groups than in the control groups, while the number of antral follicles and corpora lutea were reduced in the treatment groups. Cell proliferation rates were decreased by TAM treatment and cystic follicles were formed in the ovarian stroma. Notch 2 expression in the granulosa cells was increased following TAM administration, but no change was found in Jagged 1 expression. TAM administration suppressed follicular development and exhibited a negative effect on ovarian morphology. Our findings suggest that the Notch pathway participates in the action of TAM. We suggest that it may be useful to use Notch pathway regulators to adjust the effects of TAM on the ovary.Publication The effect of tamoxifen on IGF signaling pathway in the mouse ovary(Ankara Üniversitesi, 2019-01-01) Asmaz, Ender Deniz; Zık, Berrin; Asmaz, Ender Deniz; ZIK, BERRİN; Veteriner Fakültesi; Histoloji ve Embriyoloji Ana Bilim Dalı; 0000-0002-1053-6250.; 0000-0001-6468; AAH-9810-2021; HPG-0648-2023; O-9669-2018Tamoxifen (TAM) is one of selective estrogen receptor modulators used in breast cancer treatment and prevention. The objective of this study was to determine whether or not insulin-like growth factor-I (IGF-1) and its receptor (IGF-1R), has any role in the effect mechanism of TAM on the ovary. Experimentally, animals were divided into three groups as control group (n=20), low dose TAM treatment group (0.5 mg/mouse/day, n=20) and high dose TAM treatment group (1.5 mg/mouse/day, n=20). TAM was injected 0.5 and 1.5 mg/mouse/day for 5 days. Ovarian sections were used to examine the general structure by trichrome staining method and to determine IGF-1 and IGF-1R expressions by immunohistochemical staining method. After the experiment, the presence of atretic follicles and small cystic structures in the TAM-treated animals was determined. Also, antral follicles and the corpus luteum were much less in the high dose TAM group than in the control. TAM did not change the expression of IGF-1 in granulosa cells, but increased the expression of IGF-1R. In TAM groups, IGF-1 and IGF-1R expression were increased in oocytes of follicles and in interstitial cells depending on TAM doses. However, while IGF-1 expression was unchanged in the corpus luteum, decreased in treatment group. TAM generally stimulated IGF-1 and IGF-1R expression in a dose-dependent manner. The results suggest that IGF-1 signaling pathway is involved in the mechanism of action of TAM on the ovary. We may assert that it may be useful to use IGF-1 signaling pathway regulators to adjust the effects of TAM on the ovary.