Browsing by Author "Gorgisen, G."

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Differential Activation and Expression of Insulin Receptor Substrate 1 (Irs1) in Mononuclear Cells of Type 2 Diabetes Patients After Insulin Stimulation
(Cellular and Molecular Biology Association, 2016) Gorgisen, G.; Balci, M.K.; Celik, F.C.; Gokkaya, M.; Ozdem, S.; Ozel, D.; Ozes, O.N.
Insulin regulates the glucose homeostasis by inducing tyrosine phosphorylation of insulin receptor substrate (IRS) proteins. IRS1 is the best studied member of this family and insulin-induced Tyrosine phosphorylation of (YXXM) motifs provides docking site for SH2 domain-containing proteins. Recent studies have suggested that genetic and/or environmental factors may affect the expression and phosphorylation levels of IRS1, and these could be important for development of insulin resistance. To shed light to the molecular basis of type 2 diabetes we wanted to determine whether YXXM motifs are genetically modified in these patients. We have isolated mononuclear cells of eighteen type 2 diabetes patients and prepared genomic DNA and protein lysates from these cells. The genomic DNA was used to sequence IRS1 gene, and protein lysates were used to determine the expression and phosphotyrosine levels of IRS1 after insulin stimulation. Although, we did not detect any mutations at/or near the YXXM coding regions in patients' DNA, immunprecipitation analysis of IRS1 indicated decreased levels of expression and tyrosine phosphorylation of IRS1 in patient's samples compared to that of healthy controls. Our results suggest that mononuclear cells of patients can be used to test the levels of insulin responsiveness before therapy. © 2016 by the C.M.B. Association.
The Effects of Melatonin on Oxidative Stress and Prevention of Primordial Follicle Loss Via Activation of Mtor Pathway in the Rat Ovary
(Nature Publishing Group, 2018) Kandemir, Y. Behram; Acar, C. Aydin; Gorgisen, G.
The Effects of Melatonin on Oxidative Stress and Prevention of Primordial Follicle Loss Via Activation of Mtor Pathway in the Rat Ovary
(C M B Assoc, 2017) Kandemir, Y. Behram; Aydin, C.; Gorgisen, G.
Mammalian Target of Rapamycin (mTOR) signaling pathway has important roles in the regulation of puberty onset, gonadotropin secretion, follicular development and ovulation. Melatonin (N-acetyl-5-methoxytryptamine) is a lipophilic hormone has multiple functions in regulating the fertility. Recent studies have shown that melatonin affected the number or maturation of follicles in the ovary. The aim of this study was to investigate the effects of melatonin on mTOR expression and quantity of follicle in rat ovary. In the present study, a total of 45 female rats were randomly divided into three groups. Group 1; Control (C), Group 2: Vehicle (V) and Group 3; Melatonin (M). Melatonin was administered intraperitoneally at a dose of 50 mg/kg/day for 30 days in Melatonin group. The effects of Melatonin on the expression of mTOR and downstream components were determined by Western Blot and Reverse Transcriptase PCR analysis. Upon Western Blot and RT-PCR evaluations, we detected higher expression and activation of mTOR, P70S6K, PKCalpha, PCNA and higher numbers of primordial follicles in melatonin group compared with V and C group. In addition to this results, melatonin decreased oxidative stress markers, such as MDA, on the contrary, levels of antioxidative markers, such as CAT and GPx, were increased by melatonin in rat ovary. This study indicated that melatonin may have a significant protective effect on primordial follicles and increase the expression of mTOR and downstream components in rat ovary. Melatonin treatment may have a beneficial effect on fertility.
Evaluation of Tp53 Codon 72 Polymorphism in Esophageal Cancer Susceptibility in Eastern Anatolia Region of Turkey
(Yuzuncu Yil Universitesi Tip Fakultesi, 2021) Kaya, Z.; Almali, N.; Karan, B.M.; Gorgisen, G.
The tumor suppressor TP53 gene plays a key role in the regulation of cell cycle. Polymorphisms in this gene have been associated with many cancers including esophageal cancer (EC). Many studies in other populations have demonstrated that codon 72 polymorphism of TP53 gene contribute to the prediction of EC risk, especially in Asians. The aim of this study was to explore the effect of codon 72 polymorphism on the EC risk in eastern Turkey. The codon 72 polymorphism was genotyped by real time polymerase chain reaction (qPCR) with TaqMan SNP geno typing assay in 79 patients and 80 healthy control subjects. No statistically significant difference was observed in distribution of genotype and allele frequencies. Heterozygous Arg/Pro (CG) was the most frequent genotype in both patients and controls. Homozygous Arg/Arg (GG) genotype frequency was higher in patients than controls, but not statistically significant (p>0.05). However, tumor location in the lower part of the esophagus was significantly higher in non-C carriers (GG, Arg/Arg) compared to C-carriers (CG/CC) (p=0.01). G-carriers were also more likely to have poorer survival compared to patients with CC genotype (p=0.04). Our results suggest that the Codon 72 polymorphism was not associated with the EC in eastern Turkey. However, GG genotype (Arg/Arg) may have a role in tumor development at the lower location of the esophagus. Additionally, G carriers may exist the poorer survival compared to the non-G carriers (CC). Therefore, it is thought that individuals with CC genotype (Pro/Pro) may have better survival. © 2021, Yuzuncu Yil Universitesi Tip Fakultesi. All rights reserved.
The Role of Insulin Receptor Substrate (Irs) Proteins in Oncogenic Transformation
(C M B Assoc, 2017) Gorgisen, G.; Gulacar, I. M.; Ozes, O. N.
Insulin Receptor Substrate (IRS) proteins are the main cytoplasmic adaptor molecules involved in transducing extracellular signals from receptors to downstream proteins. This protein family have pivotal roles on maintenance, distribution and regulation of signaling networks. Since IRS1/2 interact with and transmits signals from the receptors of insulin, Insulin Like Growth Factor 1 (IGF1), prolactin, growth hormone (GH), leptin, Vascular Endothelial Growth Factor (VEGF), TrkB, ALK and integrins this promoted scientist to think that IRS1 may have functions in cell proliferation, tumorigenesis and metastasis. Therefore, over the past decade, studies on IRS proteins and their functions in cancer has been increased and these studies provided valuable results claiming the involvement of IRS1/2 in cancer development. In this review, we discuss the function and contributions of IRS1 and IRS2 in development of breast cancer.
Silibinin and Ellagic Acid Increase the Expression of Insulin Receptor Substrate 1 Protein in Ultraviolet Irradiated Rat Skin
(Taylor & Francis Ltd, 2020) Gorgisen, G.; Ozkol, H.; Tuluce, Y.; Arslan, A.; Ecer, Y.; Keskin, S.; Ragbetli, M. C.
Daily exposure to ultraviolet (UV) light induces inflammation and tumorigenesis in the skin. Silibinin and ellagic acid are natural products that exhibit anti-inflammatory and anti-tumorigenic properties. Insulin receptor substrate protein 1 (IRS1) is important for skin homeostasis and physiology, but its activity following UV radiation remains unclear. We investigated the effects of ellagic acid and silibinin on IRS1 expression in ultraviolet A (UVA) and ultraviolet B (UVB) irradiated rat skin. Forty-two female Wistar rats were divided randomly into six groups of seven animals. The dorsal skin of rats was exposed to UVA + UVB, then treated with ellagic acid and silibinin by gavage. IRS1 expression in skin tissues was determined by western blot analysis. IRS1 expression increased significantly following treatment with ellagic acid and silibinin in UVA + UVB irradiated skin compared to the UVA + UVB only group. After UVA + UVB treatment, ellagic acid effected greater induction of IRS1 expression than silibinin. Our findings suggest that the photoprotective roles of ellagic acid and silibinin may be due to induction of IRS1 expression in UVA + UVB treated rat skin.