| The lives organisms undergo progressive deleterious alterations called"aging"or"senescence". Alterations that accompany the aging phenotype are ultimately lead to structural disorganization ,functional decline and increased probability of diseases and death.There were many literature reported many neurodegenerative disease are related to aging.Including Alzheimer's disease, Parkinson's disease and Motor Neuron disease. But the exact molecule mechanism is indistinct. There were multiplicity evidience confirmed that it exist oxidative stress and iron abnomal deposite during aging and degenerative disease of the central nervous system.By understanding the proceeding and mechanism of the central nervous system aging can help us better understand of these correlated disease clinicial situation and progress.Iron is the most abundant trace element in the human body,and because of its unique chemical reactivity,it plays important roles in the maintenance of celluar and organic normal metabolic process, such as delivery of oxygen,mitoch- ondrial oxidative reaction ,the synthesis of neurotransmitter and DNA. But free iron can generate highly reactivitve hydroxy radicals through Fenton reaction,lead to oxidative stress, and damage some basic components of organism, such as lipids,proteins,DNA,and result in celluar injury. So maintanice of celluar iron balance is very important to body.Outside the brain, the balance of iron in the cell and tissue was many depend on two proteins: transferrin receptor and ferritin which were controled by celluar iron. The organism can regulate the express of thess two proteins by conjunct of intracytoplasmic iron regulatoryprotein and iron response element in the transferrin receptor and ferritin mRNA when the iron concentratoin changes in cell, so the celluar iron can main the normal degree.The express of transferrin receptor was increse and ferritin was decrese when the iron decrese,instead the anti.It has been confirmed that these exist the transferrin receptor and ferritin in the brain,and these regulate were also controled by IRP-IRE mechanism.Oxidative stress is very importand during aging which refer to the the free radical and its production in the body exceed the organism antioxidation defense mechanism,it is usually because of the internal free radical increse significant and/or the decrease of organism antioxidation defense function.Nrf2/ARE system was indispensable to resist environmental stress and endogenous stress.Nuclear-factor erythroid 2-related factor 2(Nrf2) is a kind of nuclear factor that have leucine zipper struct which exist in intracytoplasm in normal,keap1 can specific combine in N-terminal of Nrf2,so that the activity of Nrf2 is inhibit.Nrf2 can phosphorylation and diversion to cellular nucleus when inductor exist. Nrf2 in cellular nucleus can combine with antioxident response element (ARE) which is a section enhancer sequence of cis-acting element.Many detoxication enzyme and antioxidase exist ARE sequence in gene order,so ARE mediate the activation of genetic transcription that participate in oxidative stress in the cell,so the reinforce express of Nrf2/ARE system can upregulation the express of many antioxidation and detoxication enzyme and enhence corpuscular antioxidation and detoxication capability. Heme oxygenase (Ho) is a kind of protease that exist in mammal histiocyte .Ho can catalyze haem to produce biliverdin,co and iron.Biliverdin re-formation heam,both of them are drastic free radical scavenger in vivo.Co educe significant signal transduction effect in cell function and report regulation.Ho is a kind of conservative gene in evolution and have two isozyme :ho1 and ho2.Ho1 is induction type and its express can be induced by various kinds stimulus ,hypoxia ,heam,transition metal and so on. The express of ho1 can enhence corpuscular antioxidation capability protect the cell.Nicotinamide-adenine dinucleotide phosphate NADPH: quinone oxidoreductase 1(NQO1) is a kind of flavoprotein enzyme which exist in most eukaryote.Most NQO1 exist in cytoplasm,but its active also can be detect in the corpusculus,mitochondria and Golgis body. NQO1 belongto detoxication enzyme which can catalyze reduction reaction of quinone chemical compound in body by NADH or NADPH as electron donor so protect the damage made by quinone chemical compond .NQO1 participate in antioxidation reaction mediated by vitamin E which can be hold in reduction state. NQO1 also act as a reducing enzyme of CoQ which can be hold in reduction state to protect the cellular membrance.Objective:This experiment were used ICR mice as study object to investigate the change of ferritin-H,TfR,Nrf2,HO1, NQO1 in spinal cord of mice at different age to understand the proceeding and mechanism of aging in central nervous system,and help us better understand the clinical appearance and progression of these correlated disease.Methods:1 The animals were divided into 3 groups,they were respectivily 1 month,5 month and 13 month male ICR mice. Each group has 6 mice, the total was 18.2 They were sacrificed at 1 month,5 month and 13 month. Using 10% chloral hydrate anesthesia the mice,then decapitate, extract spinal cord, put it into liquid nitrogen for frozing, then stored in -80℃.3 Extract the protein of spinal cord using the kit , then measured the density of protein carries on western blotting analysis.4 The experiment data was demenstrate as mean±standard deviation ( (x|-)±s) , statistical analysis was used SAS software , statistical result is remarkable difference when P<0.05.Results:1 The express of ferritin was upregulation and TfR was downregulation in aging.Ferritin in spinal cord of mice incresed in the 13 month compare with the 1 month and 5 month(p<0.05). Ferritin in the spinal cord of mice incresed in the 5 month compare with the 1 month,but have no statistical significance. TfR in the spinal cord of mice incresed in the 13 month and 5 month compare with the 1 month (p<0.05).But the mice in the 5 month compare with the 13 month have no statistical significance.2 The express of Nrf2/ARE system downregulation in aging. Nrf2 in the spinal cord of mice decreased in the 13 month compare with the 5 month(p<0.05),the remaining group compared with each other have no statistical significance.HO1 in spinal cord of mice decrese in 5 month and 13 month compare with 1 month(p<0.05), the remaining group compared with each other have no statistical significance.NQO1 have no statistical significance in each group.Conclusions: The express of ferritin was upregulation and TfR wasl down regulation in the spinal cord of aging mice ,we presume this was the protective reaction to iron overladen.The express of Nrf2,HO1 was downregulation during aging,which wass the mark of the decrease of organism antioxidation capability.This illustrate these existed the iron metabolic disorder and oxidative stress in aging. |
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