Effects Of Aspirin On The Expression Of Iron Metabolism Related Proteins In IL-6 Treated PC-12 Cells

Iron is a kind of trace element that human body must have.It participates in a variety of physiological metabolic activities,including the composition of various proteins and key metabolic enzymes and the transmission of electrons.Under normal physiological conditions,iron metabolism in the body is in a state of equilibrium.When iron metabolism is unbalanced,it can cause iron deficiency or accumulation in the body.Excessive iron accumulation can cause the oxidative stress and inflammation and other toxic reactions of cells,causing the cell's dysfunction and even death,thus,causing further damage to the body.In Alzheimer's Disease?Parkinson's Diseaseand other Neurodegenerative Diseases,iron accumulation and neuroinflammation are commonly found.Therefore,the reduction of iron accumulation and anti-oxidative reaction is an effective way to treat neurodegenerative diseases such as AD and PD.The current treatment of iron accumulation of drugs,including deferoxamine ? deferiprone and so have a great side effects.Aspirin is a class of non-steroidal anti-inflammatories,widely used in various diseases such as anti-inflammatory?anti-rheumatism and pain treatment,and has a neuroprotective effect.In the latest study,ASA can regulate the expression of iron-related metabolic proteins in BV-2 cells in physiological and inflammatory conditions,thereby altering the intracellular iron content.Objective: This study was to investigate the effect of ASA on the expression of iron metabolism-related proteins in PC-12 cells under physiological and inflammatory conditions,and to explore the pathways of ASA.In understanding the potential mechanism of ASA's beneficial role in the inflammatory condition of AD and other neurodegenerative diseases.Method: In this study,rat adrenergic neurotransmitters pheochromocytoma cell line PC-12 cells were used as subjects to study,the inflammation model was made with interleukin-6.Using MTT investegate the effect of ASA on pc-12 cells activity under the physiological and inflammatory conditions.The effect of ASA on the expression of Ferroportin 1,Ferritin light chain,Transferrin Receptor 1?Janus kinase 2?STAT3 and other iron metabolism-related proteins under physiological and inflammatory conditions was detected by western blotting.Real-time quantitative PCR was used to detect the effects of ASA on gene expression of hepcidin in physiological and inflammatory conditions.Result: MTT showed that ASA had no significant effect on PC-12 cell viability under physiological conditions.Under inflammatory conditions,the ASA can improve the decreased cell activity caused by il-6 and 1mM ASA has a significant improvement(P < 0.05).Under the physiological conditions WB showed that ASA could significantly increase the expression of Fpn1(P <0.01),but,there was no significant difference in the expression of TfR1?Ft-L?p STAT3 and p JAK2.Under inflammatory conditions,the ASA can significantly inhibit the low expression of Fpn1 induced by IL-6(P < 0.01),and the high expression of Ft-L(P < 0.01),pSTAT3(P < 0.05)and p JAK2(P < 0.05).The results of real-time PCR showed no significant change in the expression of Hepcidin gene under physiological conditions.Under inflammatory conditions,the ASA can significantly inhibit the high expression of Hepcidin m RNA(P < 0.05).Conclusion:.The ASA can inhibit the changes in PC-12 cell-associated ironmetabolism protein caused by inflammatory factors and the decrease in cell viability.In the inflammatory condition,ASA can negatively regulate the expression of Hepcidin through the IL-6 / JAK2 / STAT3 pathway,thus enhancing the expression of Fpn1 and the iron output capacity of the cells,thereby reducing intracellular iron accumulation and the cytotoxicity damage.