Publications by authors named "F Behice Serinkan Cinemre"

8 Publications

Redox Epiphospholipidome in Programmed Cell Death Signaling: Catalytic Mechanisms and Regulation.

Front Endocrinol (Lausanne) 2020 19;11:628079. Epub 2021 Feb 19.

Exposure Assessment Branch, The National Institute for Occupational Safety and Health/Centers for Disease Control and Prevention (NIOSH/CDC), Morgantown, WV, United States.

A huge diversification of phospholipids, forming the aqueous interfaces of all biomembranes, cannot be accommodated within a simple concept of their role as membrane building blocks. Indeed, a number of signaling functions of (phospho)lipid molecules has been discovered. Among these signaling lipids, a particular group of oxygenated polyunsaturated fatty acids (PUFA), so called lipid mediators, has been thoroughly investigated over several decades. This group includes oxygenated octadecanoids, eicosanoids, and docosanoids and includes several hundreds of individual species. Oxygenation of PUFA can occur when they are esterified into major classes of phospholipids. Initially, these events have been associated with non-specific oxidative injury of biomembranes. An alternative concept is that these post-synthetically oxidatively modified phospholipids and their adducts with proteins are a part of a redox epiphospholipidome that represents a rich and versatile language for intra- and inter-cellular communications. The redox epiphospholipidome may include hundreds of thousands of individual molecular species acting as meaningful biological signals. This review describes the signaling role of oxygenated phospholipids in programs of regulated cell death. Although phospholipid peroxidation has been associated with almost all known cell death programs, we chose to discuss enzymatic pathways activated during apoptosis and ferroptosis and leading to peroxidation of two phospholipid classes, cardiolipins (CLs) and phosphatidylethanolamines (PEs). This is based on the available LC-MS identification and quantitative information on the respective peroxidation products of CLs and PEs. We focused on molecular mechanisms through which two proteins, a mitochondrial hemoprotein cytochrome (cyt ), and non-heme Fe lipoxygenase (LOX), change their catalytic properties to fulfill new functions of generating oxygenated CL and PE species. Given the high selectivity and specificity of CL and PE peroxidation we argue that enzymatic reactions catalyzed by cyt /CL complexes and 15-lipoxygenase/phosphatidylethanolamine binding protein 1 (15LOX/PEBP1) complexes dominate, at least during the initiation stage of peroxidation, in apoptosis and ferroptosis. We contrast cell-autonomous nature of CLox signaling in apoptosis correlating with its anti-inflammatory functions non-cell-autonomous ferroptotic signaling facilitating pro-inflammatory (necro-inflammatory) responses. Finally, we propose that small molecule mechanism-based regulators of enzymatic phospholipid peroxidation may lead to highly specific anti-apoptotic and anti-ferroptotic therapeutic modalities.
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http://dx.doi.org/10.3389/fendo.2020.628079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933662PMC
May 2021

Resolving the paradox of ferroptotic cell death: Ferrostatin-1 binds to 15LOX/PEBP1 complex, suppresses generation of peroxidized ETE-PE, and protects against ferroptosis.

Redox Biol 2021 01 16;38:101744. Epub 2020 Oct 16.

Children's Neuroscience Institute, University of Pittsburgh, Pittsburgh, PA, USA; Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, PA, USA; Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA; Navigational Redox Lipidomics Group, Institute for Regenerative Medicine, IM Sechenov First Moscow State Medical University, Russian Federation. Electronic address:

Hydroperoxy-eicosatetraenoyl-phosphatidylethanolamine (HpETE-PE) is a ferroptotic cell death signal. HpETE-PE is produced by the 15-Lipoxygenase (15LOX)/Phosphatidylethanolamine Binding Protein-1 (PEBP1) complex or via an Fe-catalyzed non-enzymatic radical reaction. Ferrostatin-1 (Fer-1), a common ferroptosis inhibitor, is a lipophilic radical scavenger but a poor 15LOX inhibitor arguing against 15LOX having a role in ferroptosis. In the current work, we demonstrate that Fer-1 does not affect 15LOX alone, however, it effectively inhibits HpETE-PE production by the 15LOX/PEBP1 complex. Computational molecular modeling shows that Fer-1 binds to the 15LOX/PEBP1 complex at three sites and could disrupt the catalytically required allosteric motions of the 15LOX/PEBP1 complex. Using nine ferroptosis cell/tissue models, we show that HpETE-PE is produced by the 15LOX/PEBP1 complex and resolve the long-existing Fer-1 anti-ferroptotic paradox.
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http://dx.doi.org/10.1016/j.redox.2020.101744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596334PMC
January 2021

Polymorphism of the Oxytocin Receptor (OXTR) Gene Affects the Circulating Oxytocin Receptor Levels in Late-Term Pregnancy in a Turkish Population.

Gynecol Obstet Invest 2020 12;85(4):343-351. Epub 2020 Jun 12.

Department of Obstetrics and Gynecology, Sakarya University, Faculty of Medicine, Sakarya, Turkey.

Introduction: Postterm and late-term pregnancies still remain a serious health problem, and underlying exact mechanisms are not fully elucidated. These mechanisms are influenced by many factors.

Objective: The aim of this study was to investigate the relationship between plasma oxytocin and oxytocin receptor levels and oxytocin receptor polymorphisms in term and late-term pregnant women.

Methods: Sixty-eight singleton pregnant women with late-term pregnancy and 83 singleton pregnant women with term parturition were included in this study. A comparison was performed between pregnancies and neonates born at term (37 0/7 and 41 6/7 weeks' gestation). Plasma oxytocin, oxytocin receptor, estradiol, and progesterone levels were measured by using enzyme-linked immunosorbent assay kits. TaqMan® SNP Genotyping Assays and qPCR ProbesMaster were used to investigate the polymorphisms of rs237911, rs2228485, rs53576, and rs2254298.

Results: There was not any difference in gene distributions of 4 common single-nucleotide polymorphisms of oxytocin receptor of rs237911, rs2228485, rs53576, and rs2254298 between subjects in late-term and term pregnancy groups. With rs53576 of the GG genotype, serum oxytocin levels were 21.50 ± 10.69 (ng/L) in the late-term group and 62.71 ± 18.01 (ng/L) in the term group (p = 0.049). Oxytocin receptor levels in the late-term and term pregnancy groups of the GG genotype were 17.92 ± 8.15 (pg/mL) and 45.77 ± 11.66 (pg/mL), respectively (p = 0.046).

Conclusion: Our findings suggest that the rs53576 oxytocin receptor single-nucleotide polymorphism is associated with late-term pregnancy through acting by direct modulation of oxytocin and oxytocin receptor levels.
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http://dx.doi.org/10.1159/000508074DOI Listing
February 2021

Is endocan a biochemical marker for asymptomatic target organ damage in hypertensive patients?

Anatol J Cardiol 2019 Feb;21(2):76-82

Department of Cardiology, Faculty of Medicine, Sakarya University; Sakarya-Turkey.

Objective: Identification of the asymptomatic target organ damage (AOD) helps to stratify the overall risk of cardiovascular (CV) diseases and guides a treatment decision in hypertensive patients without a symptomatic CV or renal disease. The endothelial-cell-specific molecule 1 (endocan) is regarded as a novel marker of endothelial dysfunction. Its release is increased in hypertensive patients, especially those with symptomatic CV and renal disease. In the present study, we aimed to evaluate the endocan levels in asymptomatic hypertensive patients with or without AOD.

Methods: The study included 132 asymptomatic hypertensive patients, and 101 of who had at least one AOD.

Results: Serum endocan levels did not differ between patients with and without AOD (3.81±0.78 vs. 3.83±0.63 ng/mL, p=0.88). An analysis according to the presence of any specific AOD did not show any difference between groups. No significant correlation was found between serum endocan levels and any of the continuous variables related to AOD, such as the pulse pressure, carotid intimae-media thickness, cardio-ankle vascular index, ankle-brachial index, left ventricular mass index, Sokolow-Lyon index, Cornell voltage-duration product, and estimated glomerular filtration rate.

Conclusion: Endocan may not serve as a useful biomarker at asymptomatic vascular stages of hypertension, despite its role in indicating disease severity and inflammatory activation in advanced symptomatic CV and renal disease.
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http://dx.doi.org/10.14744/AnatolJCardiol.2018.25564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457429PMC
February 2019

The correlation of serum asymmetric dimethylarginine and anti-Müllerian hormone in primary dysmenorrhea.

Kaohsiung J Med Sci 2016 Aug 27;32(8):414-9. Epub 2016 Jul 27.

Department of Cardiology, Sakarya, Sakarya University, Faculty of Medicine, Sakarya, Turkey.

In this study, we aimed to investigate the association of serum asymmetric dimethylarginine (ADMA) and anti-Müllerian hormone (AMH) levels in primary dysmenorrhea patients. The study employed a cross-sectional design. Eighty-nine female university students with primary dysmenorrhea were included in the study. All patients underwent complete clinical and laboratory investigations, including serum ADMA, AMH levels, pelvic ultrasonography, electrocardiography, and echocardiography. Pearson correlation and linear regression analysis were used to evaluate associations between continuous data. Categorical associations were evaluated using χ(2) test. Correlation analysis between serum ADMA and AMH levels in the study group showed a highly significant positive relationship (Pearson correlation = 0.978, p = 0.01). Our study has shown a significant positive correlation between serum ADMA and AMH levels in primary dysmenorrhea. Serum ADMA levels may have the potential to demonstrate ovarian reserve.
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http://dx.doi.org/10.1016/j.kjms.2016.07.001DOI Listing
August 2016