ABSTRACT
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 dyshomeostasis. 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 IRP1, 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 treatment of SNP attenuated the cell viability in a dose-dependent manner. Flow cytometry test showed that 100 and 300 μmol/L SNP administration significantly reduced the mitochondrial membrane potential by 45% and 60%, respectively. Moreover, Western blotting analysis demonstrated that 300 μmol/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.
Subject(s)
Humans , Cell Line , Cell Survival , F-Box Proteins , Metabolism , Homeostasis , Iron Regulatory Protein 2 , Metabolism , Nitric Oxide , Metabolism , Nitroprusside , Pharmacology , Proteasome Endopeptidase Complex , Ubiquitin , Metabolism , Ubiquitin-Protein Ligase Complexes , MetabolismABSTRACT
ATP-sensitive potassium channels (K), as an inward rectifying potassium channel, are widely distributed in many types of tissues. Kare activated by the depletion of ATP level and the increase in oxidative stress in cells. The activity of Kcouples cell metabolism with electrical activity and results in membrane hyperpolarization. Kare ubiquitously distributed in the brain, including substantia nigra, hippocampus, hypothalamus, cerebral cortex, dorsal nucleus of vagus and glial cells, and participate in neuronal excitability, mitochondria homeostasis and neurotransmitter release. Accumulating lines of evidence suggest that Kare the major contributing factors in the pathogenesis of Parkinson's disease (PD). This review discussed the association of Kwith the pathogenic processes of PD by focusing on the roles of Kon the degeneration of dopaminergic neurons, the functions of mitochondria, the firing pattern of dopaminergic neurons in the substantia nigra, the α-synuclein secretion from striatum, and the microglia activation.
Subject(s)
Humans , Dopaminergic Neurons , KATP Channels , Mitochondria , Oxidative Stress , Parkinson Disease , Synaptic TransmissionABSTRACT
Neural stem cells (NSCs) offer great promise for the treatment of multiple neurodegenerative diseases. However, the survival and differentiation rates of grafted cells in the host brain need to be enhanced. In this regard, understanding of the underlying mechanism of NSCs survival and death is of great importance for the implications of stem cell-based therapeutic application in the treatments of neurological disorders. Autophagy is a conserved proteolytic mechanism required for maintaining cellular homeostasis, which can affect NSCs fate through regulating their biological behaviors, such as survival and proliferation. In this mini-review, we will summarize the effects of autophagy on NSCs fate including survival, apoptosis, proliferation and differentiation, as well as the underlying mechanisms.