Browsing by Author "Baykal, Ahmet Tarik"

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Brain region-specific amyloid plaque-associated myelin lipid loss, APOE deposition and disruption of the myelin sheath in familial Alzheimer's disease mice
(WILEY, 2020-01-01) Kaya, Ibrahim; Jennische, Eva; Lange, Stefan; Baykal, Ahmet Tarik; Malmberg, Per; Fletcher, John S.
There is emerging evidence that amyloid beta (A beta) aggregates forming neuritic plaques lead to impairment of the lipid-rich myelin sheath and glia. In this study, we examined focal myelin lipid alterations and the disruption of the myelin sheath associated with amyloid plaques in a widely used familial Alzheimer's disease (AD) mouse model
Neonatal Neurodegeneration in Alzheimer's Disease Transgenic Mouse Model
(IOS PRESS, 2018-01-01) Mazi, Aise Rumeysa; Arzuman, Aysegul Sumeyye; Gurel, Busra; Sahin, Betul; Tuzuner, Mete Bora; Ozansoy, Mehmet; Baykal, Ahmet Tarik
Alzheimer's disease (AD) is a progressive disorder characterized by a variety of molecular pathologies causing cortical dementia with a prominent memory deficit. Formation of the pathology, which begins decades before the diagnosis of the disease, is highly correlated with the clinical symptoms. Several proteomics studies were performed using animal models to monitor the alterations of the brain tissue proteome at different stages of AD. However, proteome changes in the brain regions of newborn transgenic mouse model have not been investigated yet. To this end, we analyzed protein expression alterations in cortex, hippocampus and cerebellum of transgenic mice carrying five familial AD mutations (5XFAD) at neonatal day-1. Our results indicate a remarkable difference in protein expression profile of newborn 5XFAD brain with region specific variations. Additionally, the proteins, which show similar expression alteration pattern in postmortem human AD brains, were determined. Bioinformatics analysis showed that the molecular alterations were mostly related to the cell morphology, cellular assembly and organization, and neuroinflammation. Moreover, morphological analysis revealed that there is an increase in neurite number of 5XFAD mouse neurons in vitro. We suggest that, molecular alterations in the AD brain exist even at birth, and perhaps the disease is silenced until older ages when the brain becomes vulnerable.
Platelet proteome changes in dogs with congestive heart failure
(BMC, 2020-01-01) Levent, Pinar; Kocaturk, Meric; Akgun, Emel; Saril, Ahmet; Cevik, Ozge; Baykal, Ahmet Tarik; Tanaka, Ryou; Ceron, Jose Joaquin; Yilmaz, Zeki
BackgroundPlatelets play a central role in the development of cardiovascular diseases and changes in their proteins are involved in the pathophysiology of heart diseases in humans. There is lack of knowledge about the possible role of platelets in congestive heart failure (CHF) in dogs. Thus, this study aimed to investigate the changes in global platelet proteomes in dogs with CHF, to clarify the possible role of platelets in the physiopathology of this disease. Healthy-dogs (n =10) and dogs with acute CHF due to myxomatous mitral valve disease (MMVD, n=10) were used. Acute CHF was defined based on the clinical (increased respiratory rate or difficulty breathing) and radiographic findings of pulmonary edema. Dogs Blood samples were collected into tubes with acid-citrate-dextrose, and platelet-pellets were obtained by centrifuge and washing steps. Platelet-proteomes were identified using LC-MS based label-free differential proteome expression analysis method and matched according to protein database for Canis lupus familiaris.ResultsTotally 104 different proteins were identified in the platelets of the dogs being 4 out of them were significantly up-regulated and 6 down-regulated in acute CHF dogs. Guanine-nucleotide-binding protein, apolipoproteins (A-II and C-III) and clusterin levels increased, but CXC-motif-chemokine-10, cytochrome-C-oxidase-subunit-2, cathepsin-D, serine/threonine-protein-phosphatase-PP1-gamma-catalytic-subunit, creatine-kinase-B-type and myotrophin levels decreased in acute CHF dogs. These proteins are associated with several molecular functions, biological processes, signaling systems and immune-inflammatory responses.ConclusionThis study describes by first time the changes in the protein composition in platelets of dogs with acute CHF due to MMVD. Our findings provide a resource for increase the knowledge about the proteome of canine platelets and their roles in CHF caused by MMVD and could be a tool for further investigations about the prevention and treatment of this disease.
Platelets Proteomic Profiles of Acute Ischemic Stroke Patients
(PUBLIC LIBRARY SCIENCE, 2016-01-01) Cevik, Ozge; Baykal, Ahmet Tarik; Sener, Azize
Platelets play a crucial role in the pathogenesis of stroke and antiplatelet agents exist for its treatment and prevention. Through the use of LC-MS based protein expression profiling, platelets from stroke patients were analyzed and then correlated with the proteomic analyses results in the context of this disease. This study was based on patients who post ischemic stroke were admitted to hospital and had venous blood drawn within 24 hrs of the incidence. Label-free protein expression analyses of the platelets' tryptic digest was performed in triplicate on a UPLC-ESI-qTOF-MS/MS system and ProteinLynx Global Server (v2.5, Waters) was used for tandem mass data extraction. The peptide sequences were searched against the reviewed homo sapiens database (www.uniprot.org) and the quantitation of protein variation was achieved through Progenesis LC-MS software (V4.0, Nonlinear Dynamics). These Label-free differential proteomics analysis of platelets ensured that 500 proteins were identified and 83 of these proteins were found to be statistically significant. The differentially expressed proteins are involved in various processes such as inflammatory response, cellular movement, immune cell trafficking, cell-to-cell signaling and interaction, hematological system development and function and nucleic acid metabolism. The expressions of myeloperoxidase, arachidonate 12-Lipoxygenase and histidine-rich glycoprotein are involved in cellular metabolic processes, crk-like protein and ras homolog gene family member A involved in cell signaling with vitronectin, thrombospondin 1, Integrin alpha 2b, and integrin beta 3 involved in cell adhesion. Apolipoprotein H, immunoglobulin heavy constant gamma 1 and immunoglobulin heavy constant gamma 3 are involved in structural, apolipoprotein A-I, and alpha-1-microglobulin/bikunin precursor is involved in transport, complement component 3 and clusterin is involved in immunity proteins as has been discussed. Our data provides an insight into the proteins that are involved in the platelets' activation response during ischemic stroke. It could be argued that this study lays the foundation for future mechanistic studies.
Proteins associated with neutrophil degranulation are upregulated in nasopharyngeal swabs from SARS-CoV-2 patients
(PUBLIC LIBRARY SCIENCE, 2020-01-01) Akgun, Emel; Tuzuner, Mete Bora; Sahin, Betul; Kilercik, Meltem; Kulah, Canan; Cakiroglu, Hacer Nur; Serteser, Mustafa; Unsal, Ibrahim; Baykal, Ahmet Tarik
COVID-19 or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared throughout the World and currently affected more than 9 million people and caused the death of around 470,000 patients. The novel strain of the coronavirus disease is transmittable at a devastating rate with a high rate of severe hospitalization even more so for the elderly population. Naso-oro-pharyngeal swab samples as the first step towards detecting suspected infection of SARS-CoV-2 provides a non-invasive method for PCR testing at a high confidence rate. Furthermore, proteomics analysis of PCR positive and negative naso-oropharyngeal samples provides information on the molecular level which highlights disease pathology. Samples from 15 PCR positive cases and 15 PCR negative cases were analyzed with nanoLC-MS/MS to identify the differentially expressed proteins. Proteomic analyses identified 207 proteins across the sample set and 17 of them were statistically significant. Protein-protein interaction analyses emphasized pathways like Neutrophil degranulation, Innate Immune System, Antimicrobial Peptides. Neutrophil Elastase (ELANE), Azurocidin (AZU1), Myeloperoxidase (MPO), Myeloblastin (PRTN3), Cathepsin G (CTSG) and Transcobalamine-1 (TCN1) were found to be significantly altered in naso-oropharyngeal samples of SARS-CoV-2 patients. The identified proteins are linked to alteration in the innate immune system specifically via neutrophil degranulation and NETosis.
Proteomic Analysis of Kidney Preservation Solutions Prior to Renal Transplantation
(PUBLIC LIBRARY SCIENCE, 2016-01-01) Coskun, Abdurrahman; Baykal, Ahmet Tarik; Kazan, Dilek; Akgoz, Muslum; Senal, Merve Oztug; Berber, Ibrahim; Titiz, Izzet; Bilsel, Gokhan; Kilercik, Hakan; Karaosmanoglu, Kubra; Cicek, Muslum; Yurtsever, Ilknur; Yazici, Cevat
One of the main issues in kidney transplantation is the optimal functional preservation of the organ until its transplantation into the appropriate recipient. Despite intensive efforts, the functional preservation period remains limited to hours. During this time, as a result of cellular injury, various proteins, peptides, and other molecules are released by the organ into the preservation medium. In this study, we used proteomic techniques to analyze the protein profiles of preservation solutions in which organs had been preserved prior to their transplantation. Samples were obtained from the preservation solutions of 25 deceased donor kidneys scheduled for transplantation. The protein profiles of the solutions were analyzed using 2D gel electrophoresis/MALDI-TOF and LC-MS/MS. We identified and quantified 206 proteins and peptides belonging to 139 different groups. Of these, 111 proteins groups were belonging to kidney tissues. This study used proteomic techniques to analyze the protein profiles of organ preservation solutions. These findings will contribute to the development of improved preservation solutions to effectively protect organs for transplantation.
Proteomic profiling of HBV infected liver biopsies with different fibrotic stages
(BMC, 2017-01-01) Katrinli, Seyma; Ozdil, Kamil; Sahin, Abdurrahman; Ozturk, Oguzhan; Kir, Gozde; Baykal, Ahmet Tarik; Akgun, Emel; Sarac, Omer Sinan; Sokmen, Mehmet; Doganay, H. Levent; Doganay, Gizem Dinler
Background: Hepatitis B virus (HBV) is a global health problem, and infected patients if left untreated may develop cirrhosis and eventually hepatocellular carcinoma. This study aims to enlighten pathways associated with HBV related liver fibrosis for delineation of potential new therapeutic targets and biomarkers. Methods: Tissue samples from 47 HBV infected patients with different fibrotic stages (F1 to F6) were enrolled for 2D-DIGE proteomic screening. Differentially expressed proteins were identified by mass spectrometry and verified by western blotting. Functional proteomic associations were analyzed by EnrichNet application. Results: Fibrotic stage variations were observed for apolipoprotein A1 (APOA1), pyruvate kinase PKM (KPYM), glyceraldehyde 3-phospahate dehydrogenase (GAPDH), glutamate dehydrogenase (DHE3), aldehyde dehydrogenase (ALDH2), alcohol dehydrogenase (ALDH1A1), transferrin (TRFE), peroxiredoxin 3 (PRDX3), phenazine biosynthesis-like domain-containing protein (PBLD), immuglobulin kappa chain C region (IGKC), annexin A4 (ANXA4), keratin 5 (KRT5). Enrichment analysis with Reactome and Kegg databases highlighted the possible involvement of platelet release, glycolysis and HDL mediated lipid transport pathways. Moreover, string analysis revealed that HIF-1 alpha (Hypoxia-inducible factor 1-alpha), one of the interacting partners of HBx (Hepatitis B X protein), may play a role in the altered glycolytic response and oxidative stress observed in liver fibrosis. Conclusions: To our knowledge, this is the first protomic research that studies HBV infected fibrotic human liver tissues to investigate alterations in protein levels and affected pathways among different fibrotic stages. Observed changes in the glycolytic pathway caused by HBx presence and therefore its interactions with HIF-1a can be a target pathway for novel therapeutic purposes.
Proteomics analysis of mitochondrial dysfunction triggered by complex specific electron transport chain inhibitors reveals common pathways involving protein misfolding in an SH-SY5Y in vitro cell model
(TUBITAK SCIENTIFIC \& TECHNICAL RESEARCH COUNCIL TURKEY, 2017-01-01) Sahin, Betul; Baykal, Ahmet Tarik
Mitochondrial dysfunction has been previously identified in neurodegenerative diseases such as Alzheimer disease, Huntington disease, and Parkinson disease. Chemical inhibition of the mitochondrial electron transport chain (ETC) was shown to trigger symptoms in animal models similar to those observed in human neurodegenerative diseases. In order to understand the effect of mitochondrial dysfunction on the proteome level, LC-MSE-based bottom-up, label-free differential proteomics expression analysis was used to monitor protein level changes in SH-SY5Y neuroblastoma cells induced by ETC-specific inhibitors (MPTP, 3-NP, sodium azide, antimycin A, and oligomycin). A total of 379 proteins were identified across the sample set and 75 of them were found to be differentially expressed (>30\% fold change). Complex-specific inhibition of the five ETS complexes were expected to result in the aberrant regulation of different molecular pathways, but the bioinformatics analysis of the LC-MSMS data showed that the differentially expressed proteins were mostly involved in similar metabolic processes. The findings suggest that the complex-specific alterations may not be directly linked to neurodegenerative pathways, but could be considered contributors. Moreover, the proteins that showed the highest protein expression difference (>60\% fold change) are involved in pathways regarding protein-folding and response to unfolded proteins. The results indicate that protein misfolding pathways might have a central role in the genesis and progression of neurodegenerative diseases and that label-free LC-MSMS proteomics analysis is an invaluable approach for studying of molecular pathways in neurodegeneration.
Serum Proteomic Changes in Dogs with Different Stages of Chronic Heart Failure
(MDPI, 2022-01-01) Saril, Ahmet; Kocaturk, Meric; Shimada, Kazumi; Uemura, Akiko; Akgun, Emel; Levent, Pinar; Baykal, Ahmet Tarik; Prieto, Alberto Munoz; Agudelo, Carlos Fernando; Tanaka, Ryou; Ceron, Jose Joaquin; Koch, Jorgen; Yilmaz, Zeki
Simple Summary Canine MMVD is a progressive chronic disease with variable clinical signs, with some patients remaining completely asymptomatic while others develop CHF. Here, the aims of the pilot study were to evaluate serum proteins by proteomic analysis in dogs at different stages of chronic heart failure (CHF) due to degenerative mitral valve disease (MMVD), and how these proteins can change after a conventional treatment. Study revealed 157 different proteins
Transcriptomics and Proteomics Analyses Reveal JAK Signaling and Inflammatory Phenotypes during Cellular Senescence in Blind Mole Rats: The Reflections of Superior Biology
(MDPI, 2022-01-01) Inci, Nurcan; Akyildiz, Erdogan Oguzhan; Bulbul, Abdullah Alper; Turanli, Eda Tahir; Akgun, Emel; Baykal, Ahmet Tarik; Colak, Faruk; Bozaykut, Perinur
The blind mole rat (BMR), a long-living subterranean rodent, is an exceptional model for both aging and cancer research since they do not display age-related phenotypes or tumor formation. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling is a cytokine-stimulated pathway that has a crucial role in immune regulation, proliferation, and cytokine production. Therefore, the pathway has recently attracted interest in cellular senescence studies. Here, by using publicly available data, we report that JAK-STAT signaling was suppressed in the BMR in comparison to the mouse. Interestingly, our experimental results showed upregulated Jak1/2 expressions in BMR fibroblasts during the replicative senescence process. The transcriptomic analysis using publicly available data also demonstrated that various cytokines related to JAK-STAT signaling were upregulated in the late passage cells, while some other cytokines such as MMPs and SERPINs were downregulated, representing a possible balance of senescence-associated secretory phenotypes (SASPs) in the BMR. Finally, our proteomics data also confirmed cytokine-mediated signaling activation in senescent BMR fibroblasts. Together, our findings suggest the critical role of JAK-STAT and cytokine-mediated signaling pathways during cellular senescence, pointing to the possible contribution of divergent inflammatory factors to the superior resistance of aging and cancer in BMRs.
Tumor necrosis factor-alpha induced caspase-3 activation-related iNOS gene expression in ADP-activated platelets
(TUBITAK SCIENTIFIC \& TECHNICAL RESEARCH COUNCIL TURKEY, 2017-01-01) Cevik, Ozge; Adiguzel, Zelal; Baykal, Ahmet Tarik; Sener, Azize
Platelets are sensitive cells and are easily activated by different stimulants in the circulation system. It is known that tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine and plays a role in inflammation. The role of TNF-a in the apoptotic process in blood platelets is unknown. In order to study the formation of apoptosis in platelets after incubation with TNF-alpha and/or ADP, several biomarkers were chosen: phosphatidylserine (PS) exposure and P-selectin binding