Publication: Investigating the effects of pharmaceuticals and endocrine disrupting chemicals on the gene expression profiles of saccharomyces cerevisiae
Abstract
Prozac olarak da bilinen fluoksetin (FLX), hedef olmayan organizmalara karşı toksisiteye sahip farmasötikal bir maddedir. Nonilfenol (NP) önemli bir endokrin bozucu kimyasal (EBK) olup endüstriyel ve tarımsal uygulamalarda yaygın olarak kullanılmaktadır. Bu çalışmada, FLX ve NP’nin model bir ökaryotik organizma olan S. cerevisiae'nin gen ekspresyon profilleri üzerine olan etkileri sırasıyla gerçek zamanlı qPCR ve RNA-Seq analizi kullanılarak araştırılmıştır. Bu kapsamda 1, 25,100 ve 200 µM FLX’e akut olarak maruz bırakılan mayada birçok gen diferansiyel şekilde ifade edilmiştir. 4 gen 25 µM FLX maruziyetin de baskılanmış, 4 genin 100 µM FLX uygulanmasında aktivitesi artmış ve 18 genin 200 µM FLX maruziyetin de aktivitesi artmıştır. Gen ekspresyon profilleri değişen bu genler, hücre döngüsü, ısı şoku, oksidatif stres, kimyasala karşı tepki ve programlanmış hücre ölümleri mekanizmaları ile ilişkilendirilmiştir. Ayrıca, 40 döngü boyunca 2 mg/ L NP'ye maruz bırakılan mayada, 948 gen (114 gen uyarılmış, 834 gen baskılanmış) diferansiyel şekilde ifade edilmiştir. Baskılanmış genlerin çoğu, hücre döngüsü, taşıma prosesi, metabolik prosesler, kimyasala karşı tepki, hücre duvarı organizasyonu/ biyogenezi, hücre döngüsünün düzenlenmesi, organel organizasyonunun düzenlenmesi, RNA polimeraz II ile transkripsiyon ile ilişkili iken, uyarılmış genlerin çoğu ise, taşıma prosesi, kimyasala karşı tepki, hücresel solunum, hücresel iyon dengesi, metabolic prosesler, öncü ara ürün ve enerji üretimi, mayotik hücre döngüsü, RNA polimeraz II ile transkripsiyon, organel organizasyonunun düzenlenmesi ile ilişkilendirilmiştir. Bu sonuçlar FLX ve NP’nin maya hücrelerini gen ifadesi seviyesinde etkilediğini kanıtlamış ve bu kimyasalların etki mekanizmalarının anlaşılmasına katkıda bulunmuştur.
Fluoxetine (FLX) which is known as Prozac is a toxic pharmaceutical for non-target organisms. Nonylphenol (NP) which is an important EDCs is widely used in industrial and agricultural applications. In this study, the effects of FLX and NP on the gene expression profiles of S. cerevisiae which is a model eukaryotic organism were investigated using qPCR and RNA-Seq analysis, respectively. Several genes were differentially expressed in yeast exposed to 1, 25, 100, and 200 µM FLX for acute exposure. 4 genes were downregulated upon exposure to 25 µM FLX and 4 genes were upregulated for 100 µM FLX treatment, while 18 genes were upregulated under 200 µM FLX exposure. These genes which change gene expression profiles are associated with cell cycle, heat shock, oxidative stress, response to the chemical and programmed cell death process. Also, 948 genes were differentially expressed (114 upregulated and 834 downregulated) in yeast exposed to 2 mg/ L NP during 40 rounds. Most downregulated genes were related to cell cycle, transport processes, metabolic process, responses to chemicals, cell wall organization/ biogenesis, regulation of cell cycle, regulation of organelle organization, transcription by RNA polymerase II, while most of the upregulated genes are associated with transport processes, responses to chemicals, cellular respiration, cellular ion homeostasis, metabolic process, generation of precursor metabolites and energy, meiotic cell cycle, transcription by RNA polymerase II, regulation of organelle organization. These results demonstrate that FLX and NP affect the yeast cells at the gene expression level and contribute to the understanding of the mechanism of action of these chemicals.
Fluoxetine (FLX) which is known as Prozac is a toxic pharmaceutical for non-target organisms. Nonylphenol (NP) which is an important EDCs is widely used in industrial and agricultural applications. In this study, the effects of FLX and NP on the gene expression profiles of S. cerevisiae which is a model eukaryotic organism were investigated using qPCR and RNA-Seq analysis, respectively. Several genes were differentially expressed in yeast exposed to 1, 25, 100, and 200 µM FLX for acute exposure. 4 genes were downregulated upon exposure to 25 µM FLX and 4 genes were upregulated for 100 µM FLX treatment, while 18 genes were upregulated under 200 µM FLX exposure. These genes which change gene expression profiles are associated with cell cycle, heat shock, oxidative stress, response to the chemical and programmed cell death process. Also, 948 genes were differentially expressed (114 upregulated and 834 downregulated) in yeast exposed to 2 mg/ L NP during 40 rounds. Most downregulated genes were related to cell cycle, transport processes, metabolic process, responses to chemicals, cell wall organization/ biogenesis, regulation of cell cycle, regulation of organelle organization, transcription by RNA polymerase II, while most of the upregulated genes are associated with transport processes, responses to chemicals, cellular respiration, cellular ion homeostasis, metabolic process, generation of precursor metabolites and energy, meiotic cell cycle, transcription by RNA polymerase II, regulation of organelle organization. These results demonstrate that FLX and NP affect the yeast cells at the gene expression level and contribute to the understanding of the mechanism of action of these chemicals.