Person: ŞAHİNTÜRK, SERDAR
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ŞAHİNTÜRK
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SERDAR
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Publication Elabela relaxes rat pulmonary artery and trachea via BKCa, KV, and KATP channels(Elsevier, 2023-04-24) Şahintürk, Serdar; ŞAHİNTÜRK, SERDAR; Tıp Fakültesi; Fizyoloji Ana Bilim Dalı; JQA-9268-2023Objective: Elabela is a newly discovered peptide hormone. This study aimed to determine the functional effects and mechanisms of action of elabela in rat pulmonary artery and trachea.Materials and methods: Vascular rings isolated from the pulmonary arteries of male Wistar Albino rats were placed in chambers in the isolated tissue bath system. The resting tension was set to 1 g. After the equilibration period, the pulmonary artery rings were contracted with 10-6 M phenylephrine. Once a stable contraction was achieved, elabela was applied cumulatively (10-10-10-6 M) to the vascular rings. To determine the vasoactive effect mechanisms of elabela, the specified experimental protocol was repeated after the incubation of signaling pathway inhibitors and potassium channel blockers. The effect and mechanisms of action of elabela on tracheal smooth muscle were also determined by a similar protocol.Results: Elabela exhibited a concentration-dependent relaxation in the precontracted rat pulmonary artery rings (p < .001). Maximal relaxation level was 83% (pEC50: 7.947 CI95(7.824-8.069)). Removal of the endothelium, indomethacin incubation, and dideoxyadenosine incubation significantly decreased the vasorelaxant effect levels of elabela (p < .001). Elabela-induced vasorelaxation levels were significantly reduced after iberiotoxin, gly-buride, and 4-Aminopyridine administrations (p < .001). L-NAME, methylene blue, apamin, TRAM-34, anan-damide, and BaCl2 administrations did not cause a significant change in the vasorelaxant effect level of elabela (p = 1.000). Elabela showed a relaxing effect on precontracted tracheal rings (p < .001). Maximal relaxation level was 73% (pEC50: 6.978 CI95(6.791-7.153)). The relaxant effect of elabela on tracheal smooth muscle was decreased significantly after indomethacin, dideoxyadenosine, iberiotoxin, glyburide, and 4-Aminopyridine in-cubations (p < .001).Conclusions: Elabela exerted a prominent relaxant effect in the rat pulmonary artery and trachea. Intact endo-thelium, prostaglandins, cAMP signaling pathway, and potassium channels (BKCa, KV, and KATP channels) are involved in the vasorelaxant effect of elabela. Prostaglandins, cAMP signaling pathway, BKCa channels, KV channels, and KATP channels also contribute to elabela-induced tracheal smooth muscle relaxant effect.Publication Potassium channels contributes to apelin-induced vasodilation in rat thoracic aorta(Bentham Science Publ Ltd, 2022-01-01) ŞAHİNTÜRK, SERDAR; İŞBİL, NACİYE; DEMİREL, SADETTİN; ÖZYENER, FADIL; Tıp Fakültesi; Fizyoloji Ana Bilim Dalı; AAH-1641-2021; AAH-3460-2021; ACQ-9887-2022Background: Apelin is a newly discovered peptide hormone and originally discovered endogenous apelin receptor ligand. Objective: In this study, we aimed to investigate the possible roles of potassium channel subtypes in the vasorelaxant effect mechanisms of apelin. Methods: The vascular rings obtained from the thoracic aortas of the male Wistar Albino rats were placed into the isolated tissue bath system. The resting tension was set to 2 g. After the equilibration period, the aortic rings were precontracted with 10-5 M phenylephrine (PHE) or 45 mM KCl. Pyroglutamyl-apelin-13 ([Pyr1]apelin-13), which is the dominant apelin isoform in the human cardiovascular tissues and human plasma, was applied cumulatively (10(-10)-10(-6) M) to the aortic rings in the plateau phase. The experimental protocol was repeated in the presence of specific K+ channel subtype blockers to determine the role of K(+)channels in the vasorelaxant effect mechanisms of apelin. Results: [Pyr1]apelin-13 induced a concentration-dependent vasorelaxation (p < 0.001). The maximum relaxation level was approximately 52%, according to PHE-induced contraction. Tetraethylammonium, iberiotoxin, 4-Aminopyridine, glyburide, anandamide, and BaCl2 statistically significantly decreased the vasorelaxant effect level of [Pyr1]apelin-13 (p < 0.001). However, apamin didn't statistically significantly change the vasorelaxant effect level of [Pyr1]apelin-13. Conclusion: In conclusion, our findings suggest that BKCa, IKCa, Kv, K-ATP, Kir, and K-2P channels are involved in the vasorelaxant effect mechanisms of apelin in the rat thoracic aorta.Publication Vascular functional effect mechanisms of elabela in rat thoracic aorta(Elsevier Science Inc, 2022-08-01) Şahintürk, Serdar; ŞAHİNTÜRK, SERDAR; ÖZYENER, FADIL; Demirel, Sadettin; İŞBİL, NACİYE; DEMİREL, SADETTİN; Tıp Fakültesi; Fizyoloji Ana Bilim Dalı; AAH-3460-2021; AAH-1641-2021; ACQ-9887-2022Background: Elabela is a recently discovered peptide hormone. The present study aims to investigate the vasorelaxant effect mechanisms of elabela in the rat thoracic aorta.Methods: The vascular rings obtained from the thoracic aortas of the male Wistar albino rats were placed in the isolated tissue bath system. Resting tension was set to 1 gram. After the equilibration period, the vessel rings were contracted with phenylephrine or potassium chloride. Once a stable contraction was achieved, elabela-32 was applied cumulatively (10(-9)-10(-6) molar) to the vascular rings. The experimental protocol was repeated in the presence of specific signaling pathway inhibitors or potassium channel blockers to determine the effect mechanisms of elabela.Results: Elabela showed a significant vasorelaxant effect in a concentration-dependent manner (P < 0.001). The vasorelaxant effect level of elabela was significantly reduced by the apelin receptor antagonist F13A, cyclooxygenase inhibitor indomethacin, adenosine monophosphate-activated protein kinase inhibitor dorsomorphin, protein kinase C inhibitor bisindolmaleimide, large-conductance calcium-activated potassium channel blocker iberiotoxin, and intermediate-conductance calcium-activated potassium channel blocker TRAM-34 (P < 0.001). However, the vasorelaxant effect level of elabela was not significantly affected by the endothelial nitric oxide synthase inhibitor nitro-L-arginine methyl ester and mitogen-activated protein kinase inhibitor U0126.Conclusions: Elabela exhibits a prominent vasodilator effect in rat thoracic aorta. Apelin receptor, prostanoids, adenosine monophosphate-activated protein kinase, protein kinase C, and calcium-activated potassium channels are involved in the vasorelaxant effect mechanisms of elabela.Publication A novel mutation in NPR2 gene in a patient with acromesomelic dysplasia, maroteaux type(Medecine Et Hygiene, 2015-01-01) Sağ, S. Özemri; Görükmez, O.; Topak, A.; Görükmez, O.; Türe, M.; Şahintürk, S.; Gülten, T.; Yakut, T.; ÖZEMRİ SAĞ, ŞEBNEM; Görükmez, Orhan; ŞAHİNTÜRK, SERDAR; Topak, Ali; Ture, Mehmet; Gulten, Tuna; Yakut, Tahsin; Tıp Fakültesi; Tıbbi Genetik Ana Bilim Dalı; 0000-0002-9241-0896; 0000-0002-9241-0896; HNQ-2791-2023; AAH-8355-2021; ACQ-9887-2022; AFZ-0764-2022; ECY-8582-2022; EYU-9227-2022; GIS-1493-2022A novel mutation in NPR2 gene in a patient with acromesomelic dysplasia, Maroteaux type: Acromesomelic dysplasia, Maroteaux type (AMDM) is a rare autosomal recessive disease characterized by disproportionate shortening of skeletal elements, predominantly affecting the middle segments (forearms and forelegs) and distal segments (hands and feet) of appendicular skeleton. Furthermore it is related to axial skeleton and leads to wedging of vertebral bodies, with shorter dorsal margins than the ventral margins. Bartels et al. defined mutations in NPR2 gene, encoding natriuretic peptide receptor B (NPR-B), underlying Acromesomelic dysplasia, type Maroteaux. We present here molecular and clinical findings of a case with AMDM. In a patient, a novel homozygous mutation c.1435C>T p.R479X in exon 7 of NPR2 gene was found. Further testing confirmed the heterozygous carrier status of the parents. Our findings expand the spectrum of causative mutations in AMDM.Publication A novel β-lactam-aminoglycoside combination in veterinary medicine: The couse of ceftiofur and gentamicin to combat resistant Escherichia coli(Hellenic Veterinary Medical Society, 2020-04-01) Cengiz, M.; Şahintürk, P.; Hepbostancı, G.; Akalın, H.; Sonal, S.; CENGİZ, MURAT; ŞAHİNTÜRK, SERDAR; AKALIN, EMİN HALİS; SONAL, SONGÜL; HEPBOSTANCI, G.; Sağlık Bilimleri Enstitüsü; 0000-0001-7530-1279; AAU-8952-2020; ABE-5935-2020The focus of this study was to evaluate the efficacy of ceftiofur+gentamicin combination to increase the success of antimicrobial inhibition against resistant Escherichia coli (E.coli) strains isolated from animals. Interaction between drugs was determined using checkerboard method and the fractional inhibitory concentration index was interpreted as synergism, antagonism and indifference. The combination was defined as bactericidal or bacteriostatic based on the minimum bactericidal test results. Mutant prevention concentration test was used to evaluate the resistance tendency suppression potential of the combination. The synergistic effect was detected for all E. coli strains by the checkerboard method; even the strains that were resistant to the individual compounds in the combination. Based on the results of minimum bactericidal concentration test, the combination exhibited bactericidal effect against all E. coli strains. In addition, the individual mutant prevention concentrations of ceftiofur and gentamicin decreased up to 125-fold by using the combination for the inhibition of resistant E. coli strains. The results indicated that killing potential of co-use of the compounds is much stronger than their individual use. The combination achieved to decrease the mutant prevention concentrations and this can reduce the risk of emergence of single mutations during treatment done with suggested doses.Publication Cilostazol induces vasorelaxation through the activation of the enos/no/cgmp pathway, prostanoids, ampk, pkc, potassium channels, and calcium channels(Elsevier Science Inc, 2023-09-25) Şahintürk, Serdar; ŞAHİNTÜRK, SERDAR; Fen Edebiyat Fakültesi; Psikoloji Bölümü; ACQ-9887-2022Objective: This study aimed to investigate vasoactive effect mechanisms of cilostazol in rat thoracic aorta.Materials and methods: The vessel rings prepared from the thoracic aortas of the male rats were placed in the chambers of the isolated tissue bath system. The resting tone was adjusted to 1 g. Following the equilibration phase, potassium chloride or phenylephrine was used to contract the vessel rings. When achieving a steady contraction, cilostazol was applied cumulatively (10(- 8)-10(-4) M). In the presence of potassium channel blockers or signaling pathway inhibitors, the same experimental procedure was performed.Results: Cilostazol exhibited a significant vasorelaxant effect in a concentration-dependent manner (pD2: 5.94 +/- 0.94) (p < .001). The vasorelaxant effect level of cilostazol was significantly reduced by the endothelial nitric oxide synthase inhibitor L-NAME (10(-4) M), soluble guanylate cyclase inhibitor methylene blue (10 mu M), cyclooxygenase 1/2 inhibitor indomethacin (5 mu M), adenosine monophosphate-activated protein kinase inhibitor compound C (10 mu M), non-selective potassium channel blocker tetraethylammonium chloride (10 mM), large -conductance calcium-activated potassium channel blocker iberiotoxin (20 nM), voltage-gated potassium channel blocker 4-Aminopyridine (1 mM), and inward-rectifier potassium channel blocker BaCl2 (30 mu M) (p < .001). Moreover, incubation of cilostazol (10(-4) M) significantly reduced caffeine (10 mM), cyclopiazonic acid (10 mu M), and phorbol 12-myristate 13-acetate-induced (100 mu M) vascular contractions (p < .001).Conclusions: In the rat thoracic aorta, the vasodilator action level of cilostazol is quite noticeable. The vaso-relaxant effects of cilostazol are mediated by the eNOS/NO/cGMP pathway, prostanoids, AMPK pathway, PKC, potassium channels, and calcium channels.Publication Metformin relaxes rat thoracic aorta via nitric oxide, AMPK, potassium channels, and PKC(Mashhad Univ Med Sciences, 2023-09-01) Şahintürk, Serdar; ŞAHİNTÜRK, SERDAR; Tıp Fakültesi; Fizyoloji Ana Bilim Dalı; ACQ-9887-2022Objective(s): The present research aimed to identify the functional effects and underlying mechanisms of metformin on the rat thoracic aorta.Materials and Methods: Thoracic aorta segments of Wistar Albino rats were put in the chambers of an isolated tissue bath system. The resting tone was adjusted to 1 g. Following the equilibration time, potassium chloride or phenylephrine was used to contract the vascular segments. The vessel segments were cumulatively treated with metformin (10-7-10-3 M) when a steady contraction was achieved. The described experimental approach was repeated after incubations with signaling pathway inhibitors and selective blockers of potassium channels to identify the effect mechanisms of metformin.Results: Metformin had a potent vasorelaxant effect in a concentration-dependent way (P<0.001). After the endothelium was removed, the vasorelaxant effect level of metformin was significantly reduced. The level of vasorelaxant effect of metformin was increased by the maintenance of perivascular adipose tissue. Following administrations of L-NAME, methylene blue, compound C, BIM-I, and potassium channel blockers, the level of vasodilatory action of metformin was significantly reduced (P<0.001). Conclusion: According to the results of this investigation, metformin significantly relaxes the thoracic aorta segments of rats. Metformin-mediated vasorelaxation involves the activation of numerous subtypes of potassium channels, including BKCa, IKCa, Kv, Kir, and K2p channels, as well as endothelium-dependent processes, including AMPK and eNOS/NO/sGS signaling pathways. Moreover, metformin-induced vasorelaxation is mediated through PVAT activation and the PKC signaling pathway.Publication A novel mutation in the fras1 gene in a patient with fraser syndrome(Medecine Et Hygiene, 2015-01-01) Sağ, S. Özemri; Görukmez, O.; Türe, M.; Şahintürk, S.; Topak, A.; Gülten, T.; Schanze, D.; Yakut, T.; Zenker, M.; ÖZEMRİ SAĞ, ŞEBNEM; Görükmez, Orhan; Türe, Mehmet; ŞAHİNTÜRK, SERDAR; Topak, Ali; Gülten, Tuna; Yakut, Tahsin; Tıp Fakültesi; Tıbbi Genetik Ana Bilim Dalı; 0000-0002-9241-0896; AAH-8355-2021; HNQ-2791-2023; ACQ-9887-2022; AFZ-0764-2022; ECY-8582-2022; EYU-9227-2022; GIS-1493-2022A novel mutation in the FRAS1 gene in a patient with Fraser syndrome: Fraser Syndrome (FS) is a rare disease with autosomal recessive inheritance characterized by cryptophthalmus, cutaneous syndactyly, laryngeal and urogenital anomalies. Mutations in the genes FRAS1 and FREM2 encoding components of a protein complex of the extracellular matrix, and recently also mutations in GRIP1 have been found to be causative for FS. We present here molecular and clinical findings of a patient with FS who was found to have a novel homozygous frameshift mutation c.9739delA, p.(T3247Pfs*44) in exon 63 of FRAS1 gene. Further testing confirmed the heterozygous carrier status of parents.Publication A fertile patient with 45X/47XXX mosaicism(Medecine Et Hygiene, 2015-01-01) Şahintürk, Serdar; Sağ, Şebnem Özemri; Türe, Mehmet; Görükmez, Orhan; Topak, Ali; Yakut, T.; Gülten, T.; ŞAHİNTÜRK, SERDAR; ÖZEMRİ SAĞ, ŞEBNEM; Türe, Mehmet; Görükmez, Orhan; Topak, Ali; Yakut, T.; Gülten, T.; Tıp Fakültesi; Genetik Bölümü; 0000-0002-9241-0896; ACQ-9887-2022; AAH-8355-2021; HNQ-2791-2023; ECY-8582-2022; FZW-2060-2022; GIS-1493-2022; EYU-9227-2022A fertile patient with 45X/47XXX mosaicism: Turner syndrome (TS) is a sex chromosome abnormality with a frequency of 1/2,000-3,000 among female live births. Characteristic findings are short stature and gonadal dysgenesis. Short and webbed neck, low posterior hairline, broad chest, widespread nipples, cubitus valgus, short 4th and 5th metacarpals, multiple pigmented nevi, primary amenorrhea, lack of secondary sexual characteristics, cardiovascular and renal anomalies are the most common presentations. Most of the cases are infertile. Spontaneous pregnancy is unusual and the risk for congenital anomaly, spontaneous abortion, stillbirth and aneuploidy is increased. Fifty percent of the patients have classical monosomy X (45,X). However mosaicism of 45,X/47,XXX is rare and accounts for 1.7% of the TS cases. Some cases may not reflect the characteristic phenotype. Some cases with normal height, normal menstrual cyclus and fertility have been defined before. The case we present herein is a 26 years old woman who was admitted to our clinic due to recurrent pregnancy loss. In her medical history she had type 1 diabetes mellitus and endometrium cancer, in her family history her mother had recurrent pregnancy loss. The patient's first, third, fourth, fifth and sixth pregnancies had resulted in spontaneous abortions in the first trimester. She had a healthy daughter with 46,XX karyotype from her second pregnancy. A 45,X[8]/47,XXX[12] karyotype was detected by conventional cytogenetic analysis of the patient who did not have dysmorphic findings. The mosaicism was confirmed by FISH analysis with CEP X probe. Of the 100 cells evaluated, 65 of them had 3 signals of X chromosome while 35 had 1 signal. We present the case because of its scarcity in the literature.Publication Irisin dilates the rat thoracic aorta via pkc, mek1/2 signaling pathway, kv channels, skca channels, and bkca channels(Wiley, 2022-02-01) Demirel, Sadettin; Şahintürk, Serdar; ŞAHİNTÜRK, SERDAR; İşbil, Naciye; İŞBİL, NACİYE; Özyener, Fadil; ÖZYENER, FADIL; Tıp Fakültesi; Fizyoloji Ana Bilim Dalı; AAH-1641-2021; AAH-3460-2021; ACQ-9887-2022