Iron accumulation in the brain is associated with the pathogenesis of Parkinson's disease(PD),Misexpression of some iron transport and storage proteins is related to iron dyshorneostasis.Iron regulatory proteins(I...Iron accumulation in the brain is associated with the pathogenesis of Parkinson's disease(PD),Misexpression of some iron transport and storage proteins is related to iron dyshorneostasis.Iron regulatory proteins(IRPs)including IRP1 and IRP2 are cytosolic proteins that play important roles in maintaining cellular iron homeostasis.F-box and leucine-rich repeat protein 5(FBXL5)is involved in the regulation of iron metabolism by degrading IRP2 through the ubiquitin-proteasome system.Nitric oxide(NO)enhances the binding activity of IRP 1,but its effect on IRP2 is ambiguous.Therefore,in the present study,we aim to determine whether sodium nitroprusside(SNP),a NO donor,regulates FBXL5 and IRP2 expression in cultured SH-SY5Y cells.MTT assay revealed that treat-ment of SNP attenuated the cell viability in a dose-dependent manner.Flow cytometry test showed that 100 and 300 ttmol/L SNP administration significantly reduced the mitochondrial membrane potential by 45%and 60%,respectively.Moreover,Western blotting analysis demonstrated that 300 txmol/L SNP significantly increased FBXL5 expression by about 39%,whereas the expression of IRP2 was decreased by 46%,correspondingly.These findings provide evidence that SNP could induce mitochondrial dysfunction,enhance FBXL5 expression and decrease IRP2 expression in SH-SY5Y cells.展开更多
基金supported by the National Natural Science Foundation of China(No.31471114,31500837 and 31540075)Taishan Scholarship,the Key Research and Development Program of Shandong Province,China(No.2016GSF201053)+1 种基金Qingdao Municipal Science and Technology Project(No.16-6-2-2-nsh)the Shandong Provincial Natural Science Foundation of China(No.BS2015SW022)
文摘Iron accumulation in the brain is associated with the pathogenesis of Parkinson's disease(PD),Misexpression of some iron transport and storage proteins is related to iron dyshorneostasis.Iron regulatory proteins(IRPs)including IRP1 and IRP2 are cytosolic proteins that play important roles in maintaining cellular iron homeostasis.F-box and leucine-rich repeat protein 5(FBXL5)is involved in the regulation of iron metabolism by degrading IRP2 through the ubiquitin-proteasome system.Nitric oxide(NO)enhances the binding activity of IRP 1,but its effect on IRP2 is ambiguous.Therefore,in the present study,we aim to determine whether sodium nitroprusside(SNP),a NO donor,regulates FBXL5 and IRP2 expression in cultured SH-SY5Y cells.MTT assay revealed that treat-ment of SNP attenuated the cell viability in a dose-dependent manner.Flow cytometry test showed that 100 and 300 ttmol/L SNP administration significantly reduced the mitochondrial membrane potential by 45%and 60%,respectively.Moreover,Western blotting analysis demonstrated that 300 txmol/L SNP significantly increased FBXL5 expression by about 39%,whereas the expression of IRP2 was decreased by 46%,correspondingly.These findings provide evidence that SNP could induce mitochondrial dysfunction,enhance FBXL5 expression and decrease IRP2 expression in SH-SY5Y cells.
