Person: YILMAZ, BETÜL
Loading...
Email Address
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
YILMAZ
First Name
BETÜL
Name
7 results
Search Results
Now showing 1 - 7 of 7
Publication Open Access Potential role of proteasome on c-jun related signaling in hypercholesterolemia induced atherosclerosis(ELSEVIER SCIENCE BV, 2014) SÖZEN, AHMET ERDİ; Sozen, Erdi; Karademir, Betul; Yazgan, Burak; Bozaykut, Perinur; Ozer, Nesrin KartalAtherosclerosis and its complications are major causes of death all over the world. One of the major risks of atherosclerosis is hypercholesterolemia. During atherosclerosis, oxidized low density lipoprotein (oxLDL) regulates CD36-mediated activation of c-jun amino terminal kinase-1 (JNK1) and modulates matrix metalloproteinase (MMP) induction which stimulates inflammation with an invasion of monocytes. Additionally, inhibition of proteasome leads to an accumulation of c-jun and phosphorylated c-jun and activation of activator protein-1 (AP-1) related increase of MMP expression. We have previously reported a significant increase in cluster of differentiation 36 (CD36) mRNA levels in hypercholesterolemic rabbits and shown that vitamin E treatment prevented the cholesterol induced increase in CD36 mRNA expression. In the present study, our aim is to identify the signaling molecules/transcription factors involved in the progression of atherosclerosis following CD36 activation in an in vivo model of hypercholesterolemic (induced by 2% cholesterol containing diet) rabbits. In this direction, proteasomal activities by fluorometry and c-jun, phospo c-jun, JNK1, MMP-9 expressions by quantitative RT-PCR and immunoblotting were tested in aortic tissues. The effects of vitamin E on these changes were also investigated in this model. As a result, c-jun was phosphorylated following decreased proteasomal degradation in hypercholesterolemic group. MMP-9 expression was also increased in cholesterol group rabbits contributing to the development of atherosclerosis. In addition, vitamin E showed its effect by decreasing MMP-9 levels and phosphorylation of c-jun. (C) 2014 The Authors. Published by Elsevier B.V.Publication Metadata only CD36 expression in peripheral blood mononuclear cells reflects the onset of atherosclerosis(WILEY, 2018) SÖZEN, AHMET ERDİ; Yazgan, Burak; Sozen, Erdi; Karademir, Betul; Ustunsoy, Seyfettin; Ince, Umit; Zarkovic, Neven; Ozer, Nesrin KartalTogether with complex genetic and environmental factors, increased serum cholesterol and ox-LDL levels are considered as major triggering factors of atherosclerosis. Mononuclear cell infiltration to the arterial wall and uptake of ox-LDL, which is facilitated by CD36 receptor through an uncontrolled manner, play a key role in foam cell formation followed by atherogenesis development. The aim of this study was to analyze if CD36 expression in peripheral blood mononuclear cells reflect its aortic tissue level in hypercholesterolemia. In this study, CD36 protein expression was evaluated in aortic specimens of cholesterol or cholesterol plus Vitamin E treated animals in relation to the immunohistochemical analyses for the HNE-protein adducts, as well as for smooth muscle actin and vimentin. The CD36 mRNA expression was determined by RT-PCR in PBMC of hypercholesterolemic rabbits and hypercholesterolemic versus normocholesterolemic individuals. Immunohistochemistry findings revealed that smooth muscle actin, smooth muscle vimentin, HNE-protein conjugates, and CD36 protein expressions were significantly increased in aorta of hypercholesterolemic group where foam cells were present. High cholesterol diet significantly induced CD36 mRNA expression in both rabbit aorta and PBMCs, while positive correlation between aortic and PBMC CD36 expression has been found. In addition, consistent with the rabbit model, CD36 mRNA expression levels in human PBMCs were significantly higher in hypercholesterolemic patients than in normocholesterolemic individuals. Taken together, these results demonstrate that the CD36 mRNA levels of PBMCs could reflect the CD36 mRNA levels in aorta and could be used as a biomarker for diagnosis of atherosclerotic burden. (c) 2018 BioFactors, 44(6):588-596, 2018Publication Metadata only Basic mechanisms in endoplasmic reticulum stress and relation to cardiovascular diseases(ELSEVIER SCIENCE INC, 2015) SÖZEN, AHMET ERDİ; Sozen, Erdi; Karademir, Betul; Ozer, Nesrin KartalThe folding process is an important step in protein synthesis for the functional shape or conformation of the protein. The endoplasmic reticulum (ER) is the main organelle for the correct folding procedure, which maintains the homeostasis of the organism. This process is normally well organized under unstressed conditions, whereas it may fail under oxidative and ER stress. The unfolded protein response (UPR) is a defense mechanism that removes the unfolded/misfolded proteins to prevent their accumulation, and two main degradation systems are involved in this defense, including the proteasome and autophagy. Cells decide which mechanism to use according to the type, severity, and duration of the stress. If the stress is too severe and in excess, the capacity of these degradation mechanisms, proteasomal degradation and autophagy, is not sufficient and the cell switches to apoptotic death. Because the accumulation of the improperly folded proteins leads to several diseases, it is important for the body to maintain this balance. Cardiovascular diseases are one of the important disorders related to failure of the UPR. Especially, protection mechanisms and the transition to apoptotic pathways have crucial roles in cardiac failure and should be highlighted in detailed studies to understand the mechanisms involved. This review is focused on the involvement of the proteasome, autophagy, and apoptosis in the UPR and the roles of these pathways in cardiovascular diseases. (C) 2014 Elsevier Inc. All rights reserved.Publication Open Access HSP70 Inhibition Leads to the Activation of Proteasomal System under Mild Hyperthermia Conditions in Young and Senescent Fibroblasts(HINDAWI LTD, 2020-02-28) SÖZEN, AHMET ERDİ; Bozaykut, Perinur; Sozen, Erdi; Kaga, Elif; Ece, Asli; Ozaltin, Esra; Bergquist, Jonas; Ozer, Nesrin Kartal; Yilmaz, Betul KarademirAging has been characterized with the accumulation of oxidized proteins, as a consequence of progressive decline in proteostasis capacity. Among others, proteasomal system is an efficient protein turnover complex to avoid aggregation of oxidized proteins. Heat shock protein 70 (HSP70) is another critical player that is involved in some key processes including the correct folding of misfolded proteins and targeting aggregated proteins to the proteasome for rapid degradation. The aim of this study was to determine the role of proteasomal system and heat shock proteins to maintain proteome balance during replicative senescence in mild hyperthermia conditions. Our results demonstrated that HSP40/70 machinery is induced by mild hyperthermia conditions independent from senescence conditions. Since HSP70 is largely responsible for the rapidly inducible cell protection following hyperthermia, the activation of heat shock response resulted in the elevation of HSP40/70 expressions as well as the proteasome activity. Interestingly, when HSP70 expression was inhibited, increased proteasomal activation was shown to be responsive to mild hyperthermia. Since HSP70 is involved in various stress-related pathways such as oxidative and endoplasmic reticulum stress, depletion of HSP70 expression may induce proteasomal degradation to maintain proteome balance of the cell. Thus, our data suggests that in mild heat stress conditions, molecular chaperone HSP70 plays an important role to avoid protein oxidation and aggregation; however, activities of proteasomal system are induced when HSP70 expression is depleted.Publication Metadata only Effects of vitamin E on peroxisome proliferator-activated receptor gamma and nuclear factor-erythroid 2-related factor 2 in hypercholesterolemia-induced atherosclerosis(ELSEVIER SCIENCE INC, 2014) SÖZEN, AHMET ERDİ; Bozaykut, Perinur; Karademir, Betul; Yazgan, Burak; Sozen, Erdi; Siow, Richard C. M.; Mann, Giovanni E.; Ozer, Nesrin KartalAtherosclerosis and associated cardiovascular complications such as stroke and myocardial infarction are major causes of morbidity and mortality. We have previously reported a significant increase in mRNA levels of the scavenger receptor CD36 in aortae of cholesterol-fed rabbits and shown that vitamin E treatment attenuated increased CD36 mRNA expression. In the present study, we further investigated the redox signaling pathways associated with protection against atherogenesis induced by high dietary cholesterol and correlated these with CD36 expression and the effects of vitamin E supplementation in a rabbit model. Male albino rabbits were assigned to either a control group fed with a low vitamin E diet alone or a test group fed with a low vitamin E diet containing 2% cholesterol in the absence or presence of daily intramuscular injections of vitamin E (50 mg/kg). To elucidate the mechanisms by which vitamin E supplementation alters the effects of hypercholesterolemia in rabbit aortae, we measured peroxisome proliferator-activated receptor gamma (PPAR gamma), ATP-binding cassette transporter A1 (ABCA1), and matrix metalloproteinase-1 (MMP-1) mRNA levels by quantitative RT-PCR and the expression of MMP-1, nuclear factor-erythroid 2-related factor 2 (Nrf2), and glutathione S-transferase alpha (GST alpha) protein by immunoblotting. The increased MMP-1 and decreased GSTa expression observed suggests that a cholesterol-rich diet contributes to the development of atherosclerosis, whereas vitamin E supplementation affords protection by decreasing MMP-1 and increasing PPAR gamma, GSTa, and ABCA1 levels in aortae of rabbits fed a cholesterol-rich diet. Notably, protein expression of Nrf2, the antioxidant transcription factor, was increased in both the cholesterol-fed and the vitamin E-supplemented groups. Although Nrf2 activation can promote CD36-mediated cholesterol uptake by macrophages, the increased induction of Nrf2-mediated antioxidant genes is likely to contribute to decreased lesion progression. Thus, our study demonstrates that Nrf2 can mediate both pro- and antiatherosclerotic effects. (C) 2014 Elsevier Inc. All rights reserved.Publication Metadata only The role of heat stress on the age related protein carbonylation(ELSEVIER SCIENCE BV, 2013) SÖZEN, AHMET ERDİ; Bozaykut, Perinur; Sozen, Erdi; Kaga, Elif; Ece, Asli; Ozaltin, Esra; Ek, Bo; Ozer, Nesrin Kartal; Grune, Tilman; Bergquist, Jonas; Karademir, BetulSince the proteins are involved in many physiological processes in the organisms, modifications of proteins have important outcomes. Protein modifications are classified in several ways and oxidative stress related ones take a wide place. Aging is characterized by the accumulation of oxidized proteins and decreased degradation of these proteins. On the other hand protein turnover is an important regulatory mechanism for the control of protein homeostasis. Heat shock proteins are a highly conserved family of proteins in the various cells and organisms whose expressions are highly inducible during stress conditions. These proteins participate in protein assembly, trafficking, degradation and therefore play important role in protein turnover. Although the entire functions of each heat shock protein are still not completely investigated, these proteins have been implicated in the processes of protection and repair of stress-induced protein damage. This study has focused on the heat stress related carbonylated proteins, as a marker of oxidative protein modification, in young and senescent fibroblasts. The results are discussed with reference to potential involvement of induced heat shock proteins. This article is part of a Special Issue entitled: Protein Modifications. Biological significance Age-related protein modifications, especially protein carbonylation take a wide place in the literature. In this direction, to highlight the role of heat shock proteins in the oxidative modifications may bring a new aspect to the literature. On the other hand, identified carbonylated proteins in this study confirm the importance of folding process in the mitochondria which will be further analyzed in detail. (C) 2013 Elsevier B.V. All rights reserved.Publication Metadata only The role of hypercholesterolemic diet and vitamin E on Nrf2 pathway, endoplasmic reticulum stress and proteasome activity(ELSEVIER SCIENCE INC, 2014) SÖZEN, AHMET ERDİ; Perinur, Bozaykut; Erdi, Sozen; Burak, Yazgan; Betul, Karademir; Nesrin, Kartal-Ozer