Metilsülfonilmetan, glukozamin ve kondroitin sülfatın LPS/IFN-? ile uyarılmış RAW 264.7 makrofaj hücrelerinde apoptoz üzerine etkileri
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Date
2011
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Sağlık Bilimleri Enstitüsü
Abstract
Apoptosis 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.
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Metilsülfonilmetan, glukozamin