PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7645
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Article Citation - WoS: 13Citation - Scopus: 15The Role of Cycloastragenol at the Intersection of Nrf2/Are, Telomerase, and Proteasome Activity(Elsevier, 2022) Yılmaz, Sinem; Bedir, Erdal; Ballar Kırmızıbayrak, PetekAging is well-characterized by the gradual decline of cellular functionality. As redox balance, proteostasis, and telomerase systems have been found to be associated with aging and age-related diseases, targeting these systems with small compounds has been considered a promising therapeutic approach. Cycloastragenol (CA), a small molecule telomerase activator obtained from Astragalus species, has been reported to positively affect several age-related pathophysiologies, but the mechanisms underlying CA activity have yet to be reported. Here, we presented that CA increased NRF2 nuclear localization and activity leading to upregulation of cytoprotective enzymes and attenuation of oxidative stress-induced ROS levels. Furthermore, CA-mediated induction of telomerase activity was found to be regulated by NRF2. CA not only increased the expression of hTERT but also its nuclear localization via upregulating the Hsp90-chaperon complex. In addition to modulating nuclear hTERT levels at unstressed conditions, CA alleviated oxidative stress-induced mitochondrial hTERT levels while increasing nuclear hTERT levels. Concomitantly, H2O2-induced mitochondrial ROS level was found to be significantly decreased by CA administration. Our data also revealed that CA strongly enhanced proteasome activity and assembly. More importantly, the proteasome activator effect of CA is dependent on the induction of telomerase activity, which is mediated by NRF2 system. In conclusion, our results not only revealed the cross-talk among NRF2, telomerase, and proteasome systems but also that CA functions at the intersection of these three major aging-related cellular pathways.Article Citation - WoS: 9Citation - Scopus: 10Characterization of Long Living Yeast Deletion Mutants That Lack Mitochondrial Metabolism Genes Dss1, Ppa2 and Afg3(Elsevier, 2019) Muid, Khandaker Ashfaqul; Kimyon, Önder; Reza, Shahadat Hasan; Karakaya, Hüseyin Çağlar; Koç, AhmetMolecular mechanisms of aging and longevity are still mostly unknown. Mitochondria play central roles in cellular metabolism and aging. In this study, we identified three deletion mutants of mitochondrial metabolism genes (ppa2 Delta, dss1 Delta, and afg3 Delta) that live longer than wild-type cells. These long-lived cells harbored significantly decreased amount of mitochondria] DNA (mtDNA) and reactive oxygen species (ROS). Compared to the serpentine nature of wild-type mitochondria, a different dynamics and distribution pattern of mitochondria were observed in the mutants. Both young and old long-lived cells produced relatively low but adequate levels of ATP for cellular activities. The status of the retrograde signaling was checked by expression of CIT2 gene and found activated in long-lived mutants. The mutant cells were also profiled for their gene expression patterns, and genes that were differentially regulated were determined. All long-lived cells comprised similar pleiotropic phenotype regarding mitochondrial dynamics and functions. Thus, this study suggests that DSS1, PPA2, and AFG3 genes modulate the lifespan by altering the mitochondrial morphology and functions.Article Citation - WoS: 28Citation - Scopus: 31Sustainable Recovery of Waste Vegetable Cooking Oil and Aged Bitumen: Optimized Modification for Short and Long Term Aging Cases(Elsevier, 2020) Uz, Volkan Emre; Gökalp, İslamBitumen ages in the short and long-term due to environmental conditions. As the bitumen ages, it loses its original properties and flexibility. Hardened bitumen causes certain distresses in pavement that may endanger traffic safety and reduce travel comfort. Bitumen is one of recoverable material, however some techniques may not be ecological due to considerable energy, time, and cost. On the other hand, recovering of aged bitumen might be eco-friendlier, energy-efficient, and economic by using bio-based waste materials such as waste vegetable cooking oils (WVCO). In this perspective, this paper was established on the idea of sustainable recovery of aged bitumen and WVCO. Base bitumen was aged in case of short-term (ST) and long-term (LT) in laboratory condition and modified with WVCO ranging from 2 to 10% by weight of bitumen. To determine the effect of WVCO modification on aged bitumen conventional and rheological test methods were utilized. To find the optimum rate of WVCO for full recovery of aged bitumen, an index called Pure Rejuvenation Index (PRI) was specified and applied for each test results. It can be concluded from PRI analyses that WVCO can be used as rejuvenator to recover aged bitumen and approximately 3% and 6% of WVCO are required for ST and LT aged bitumen cases, respectively. However, different test methods yield different optimum rates of WVCO for ST and LT aged bitumen. Recovering of WVCO and aged bitumen by using together may provide environmental protection and conservation of resources.Article Citation - WoS: 19Citation - Scopus: 22Absence of Superoxide Dismutase Activity Causes Nuclear Dna Fragmentation During the Aging Process(Academic Press Inc., 2014) Muid, Khandaker Ashfaqul; Karakaya, Hüseyin Çaglar; Koç, AhmetSuperoxide dismutases (SOD) serve as an important antioxidant defense mechanism in aerobic organisms, and deletion of these genes shortens the replicative life span in the budding yeast Saccharomyces cerevisiae. Even though involvement of superoxide dismutase enzymes in ROS scavenging and the aging process has been studied extensively in different organisms, analyses of DNA damages has not been performed for replicatively old superoxide dismutase deficient cells. In this study, we investigated the roles of SOD1, SOD2 and CCS1 genes in preserving genomic integrity in replicatively old yeast cells using the single cell comet assay. We observed that extend of DNA damage was not significantly different among the young cells of wild type, sod1Δ and sod2Δ strains. However, ccs1Δ mutants showed a 60% higher amount of DNA damage in the young stage compared to that of the wild type cells. The aging process increased the DNA damage rates 3-fold in the wild type and more than 5-fold in sod1Δ, sod2Δ, and ccs1Δ mutant cells. Furthermore, ROS levels of these strains showed a similar pattern to their DNA damage contents. Thus, our results confirm that cells accumulate DNA damages during the aging process and reveal that superoxide dismutase enzymes play a substantial role in preserving the genomic integrity in this process.Article Citation - WoS: 12Citation - Scopus: 12Identification of Respiratory Chain Gene Mutations That Shorten Replicative Life Span in Yeast(Elsevier Ltd., 2012) Hacıoğlu, Elise; Demir, Ayşe Banu; Koç, AhmetAging is the progressive accumulation of alterations in cells that elevates the risk of death. The mitochondrial theory of aging postulates that free radicals produced by the mitochondrial respiratory system contribute to the aging process. However, the roles of individual electron transfer chain (ETC) components in cellular aging have not been elucidated. In this study, we analyzed the replicative life span of 73 yeast deletion mutants lacking the genes of the mitochondrial electron transfer chain system, and found that nine of these mutants (δ nde1, δ tcm62, δ rip1, δ cyt1, δ qrc8, δ pet117, δ cox11, δ atp11, δ fmc1) had significantly shorter life spans. These mutants had lower rates of respiration and were slightly sensitive to exogenous administration of hydrogen peroxide. However, only two of them, δ nde1 and δ fmc1, produced higher amounts of intrinsic superoxide radicals in the presence of glucose compared to that of wild type cells. Interestingly, there were no significant alterations in the mitochondrial membrane potentials of these mutants. We speculate that the shorter life spans of ETC mutants result from multiple mechanisms including the low respiration rate and low energy production rather than just a ROS-dependent path. © 2011 Elsevier Inc.Article Citation - WoS: 7Citation - Scopus: 7The Roles of Thiol Oxidoreductases in Yeast Replicative Aging(Elsevier Ltd., 2010) Hacıoğlu, Elise; Esmer, Işıl; Fomenko, Dmitri E.; Gladyshev, Vadim N.; Koç, AhmetThiol-based redox reactions are involved in the regulation of a variety of biological functions, such as protection against oxidative stress, signal transduction and protein folding. Some proteins involved in redox regulation have been shown to modulate life span in organisms from yeast to mammals. To assess the role of thiol oxidoreductases in aging on a genome-wide scale, we analyzed the replicative life span of yeast cells lacking known and candidate thiol oxidoreductases. The data suggest the role of several pathways in controlling yeast replicative life span, including thioredoxin reduction, protein folding and degradation, peroxide reduction, PIP3 signaling, and ATP synthesis. © 2010 Elsevier Ireland Ltd.Article Citation - WoS: 29Citation - Scopus: 29Methionine Sulfoxide Reduction and the Aging Process(John Wiley and Sons Inc., 2007) Koç, Ahmet; Gladyshev, Vadim N.Aging has been described for multicellular and asymmetrically dividing organisms, but the mechanisms are poorly understood. Oxidation of proteins is considered to be one of the major factors that leads to aging. Oxidative damage to proteins results in the oxidation of certain amino acid residues, among which oxidation of sulfur-containing amino acids, methionine and cysteine, is notable because of the susceptibility of these residues to damage, and occurrence of repair mechanisms. Methionine sulfoxide reductases, MsrA and MsrB, are thioredoxin-dependent oxidoreductases that reduce oxidized forms of methionine, methionine sulfoxides, in a stereospecific manner. These enzymes are present in all cell types and have shown to be regulating life spans in mammals, insects, and yeast. Here, their roles in modulating yeast life span are discussed.Article Citation - WoS: 59Citation - Scopus: 60Effects of Deleting Mitochondrial Antioxidant Genes on Life Span(John Wiley and Sons Inc., 2007) Ünlü, Ercan Selçuk; Koç, AhmetReactive oxygen species (ROS) damage biomolecules, accelerate aging, and shorten life span, whereas antioxidant enzymes mitigate these effects. Because mitochondria are a primary site of ROS generation and also a primary target of ROS attack, they have become a major focus area of aging studies. Here, we employed yeast genetics to identify mitochondrial antioxidant genes that are important for replicative life span. In our studies, it was found that among the known mitochondrial antioxidant genes (TTR1, CCD1, SOD1, GLO4, TRR2, TRX3, CCS1, SOD2, GRX5, PRX1), deletion of only three genes, SOD1 (Cu, Zn superoxide dismutase), SOD2 (Manganese-containing superoxide dismutase), and CCS1 (Copper chaperone), shortened the life span enormously. The life span decreased 40% for Δsod1 mutant, 72% for Δsod2 mutant, and 50% for Δccs1 mutant. Deletion of the other genes had little or no effect on life span.