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- W448013352 abstract "Apoptoz, doku homeostazisinin duzenlenmesi gibi normal fizyolojide ve cesitli hastaliklarin patofizyolojisinde onemli rol oynayan, genetik olarak programlanmis bir hucre olum mekanizmasidir. Apoptoz, icsel ve dissal olmak uzere baslica iki yolak araciligi ile gerceklesir. Bircok hucre tipinde mikrobiyal ve viral patojenlere karsi savunma mekanizmasi olarak iNOS enziminin aktivasyonu sonucunda sentezlenen nitrik oksit, apoptozun icsel yolak aracili indukleyicileri arasinda yer almaktadir. Nitrik oksitin kontrolsuz uretimi, apoptotik yolaklarin da etkin oldugu ateroskleroz, romatoid artrit, diyabet, septik sok ve multipl skleroz gibi inflammatuvar ve immun patolojilerde rol oynamaktadir. Son yillarda, ozellikle temelinde inflamatuvar bozukluklarin yattigi artrit ve romatoid artrit tedavisinde yarar sagladigi one surulen MSM ve MSM ile kombine preparatlari bulunan GA ve CS klinikte yaygin olarak kullanilmaktadir. Literaturde MSM' nin apoptotik yolaklar uzerindeki etki mekanizmalarina iliskin yeterli bilgi bulunmamaktadir. Ayrica, klinikte bu uc kimyasal maddenin farkli kombine formlarinin kullaniliyor olusu, tek basina sergiledikleri etkilerin yani sira kombine olarak uygulanmalari durumunda sergiledikleri etkilerin belirlenmesini onemli kilmaktadir. Bu calismada, MSM, GA ve CS' nin farkli konsantrasyonlarda tek basina ve/veya kombine uygulandiklarinda LPS/IFN? ile aktive RAW 264.7 makrofajlarda apoptoz uzerine olan etkileri belirlenmistir. Bu amacla, nitrit duzeyleri ve hucre canliligi tayin edilmis ve apoptozun belirtecleri arasinda yer alan kaspaz-3 aktivitesi, mitokondri membran potansiyeli ve Ann V-PI ile akim sitometrik analizler gerceklestirilmistir. Kimyasal maddelerin tamami nitrit duzeyleri uzerinde inhibe edici etki gostermisler, en etkin inhibisyon 100 mM MSM ile gerceklesmistir. MSM' nin LPS/IFN? ile aktive RAW 264.7 makrofajlarda doz bagimli olarak apoptotik ya da antiapoptotik olarak davrandigi, GA' nin ise uygulanan butun dozlarda mitokondri membran potansiyelini arttirdigi, kaspaz-3 enzim aktivitesini azalttigi ve antiapoptotik etkiler gosterdigi belirlenmistir. CS, tek basina uygulanmasi durumunda apoptotik belirtecler uzerine etki gostermezken MSM ve GA ile kombine formlari antiapoptotik etkiler gostermistir. Kombine formlarda gozlenen antiapoptotik etkilerin buyuk olcude GA' nin etkisinden kaynaklanabilecegi dusunulmektedir. GA' nin aktive hucrelerde nitrit duzeylerinde yarattigi inhibisyonun cok guclu olmamasi nedeniyle antiapoptotik etkilerine kismen nitrit sentezi uzerine olan etkilerinin aracilik ettigi, bununla birlikte nitrik oksit bagimli olmayan yolaklarin da gorev yaptigi dusunulmektedir. MSM ve GA' nin nitrit uretimi uzerinde inhibitor etkiler sergilerken hucre canliligi ve apoptoz uzerine birbirinden farkli etkiler gostermeleri ise makrofajlarda LPS/IFN? uyarimi ile aktive olan cok sayida biyolojik sinyal yolaginin bulunmasi ve sozu gecen kimyasal maddelerin olasilikla farkli sinyal yolaklarina etkileri ile aciklanabilir. Bu nedenle MSM, GA ve CS' nin spesifik yolaklar uzerine olan etkilerini aydinlatmak uzere mekanizmaya yonelik daha ayrintili calismalarin yapilmasi gerekmektedir.AbstractApoptosis is a genetically programmed cell death mechanism which plays important role in normal physiology such as tissue homeostasis regulation and pathophsiology of various diseases. Apoptosis occurs mainly via two pathways, intrinsic and extrinsic. iNOS enzyme activation and nitric oxide synthesis in various cell types as a defense mechanism against microbial and viral pathogens plays important role in inflammatory and immune pathologies such as atherosclerosis, rheumatoid arthritis, diabetes, septic shock and multiple sclerosis, highly and uncontrolled production of nitric oxide leads to cell death. Recently, MSM and GA and CS which are acclaimed to be beneficial for inflammatory disorders arthritis and romatoid arthritis are used widely clinically. There is limited information regarding the effect mechanisms of MSM on apoptotic pathways. Furthermore as these three chemical agents are widely prescript together, it is important to analyse the effects of MSM, GA and CS both alone and in combination. In this study, effects of different concentrations of MSM, GA and CS alone or in combination were tested on LPS/IFN? activated RAW 264.7 macrophages. Fort his purpose nitrite levels, cell viability, caspase-3 activity, mitochondria membran potential and flow cytometric analysis with Annexin V-PI cell staining was performed. All of the compounds tested inhibited nitrite levels, most potent inhibition was achieved with 100 mM MSM. MSM acted as apoptotic or antiapoptotic in LPS/IFN? activated macrophages depending on the dose tested whereas GA increased mitochondrial membrane potential, decreased caspase-3 enzyme activity and exhibited antiapoptotic effects. CS did not effect any apoptotic revealers alone, however its combination with MSM and/or GA showed antiapoptotic effects which might be largely attributed to GA. As the inhibitor effect of GA on activated cells is not potent, the antiapoptotic effects of GA is partly nitric oxide dependent however nitric oxide independent pathways are thought to be responsible. MSM and GA both inhibited NO levels but they showed opposite effects in terms of cell viability and apoptosis. This can be explained with activation of various different biological signal pathways in macrophages with LPS/IFN? and the probable effects of the chemicals on different signaling pathways. In this regard, further elaborate studies are needed to clarify the effects of MSM, GA and CS on mechanisms in specific pathways." @default.
- W448013352 created "2016-06-24" @default.
- W448013352 creator A5057192574 @default.
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- W448013352 date "2011-01-01" @default.
- W448013352 modified "2023-09-23" @default.
- W448013352 title "Metilsülfonilmetan, glukozamin ve kondroitin sülfatın LPS/IFN-y ile uyarılmış RAW 264.7 makrofaj hücrelerinde apoptoz üzerine etkileri" @default.
- W448013352 doi "https://doi.org/10.1501/ankara-26759" @default.
- W448013352 hasPublicationYear "2011" @default.
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