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1.
To verify the antioxidative role of SelW in oxidant-induced chicken splenic lymphocyte, in this report, the influence of selenite supplementation and SelW gene silence on H 2O 2-mediated cell viability and cell apoptosis in cultured splenic lymphocyte derived from spleen of chicken were examined. The cultured cells were treated with sodium selenite and H 2O 2, or knocked down SelW with small interfering RNAs (siRNAs). The lymphocytes were examined for cell viability, cell apoptosis and mRNA expression levels of SelW and apoptosis-related genes (Bcl-2, Bax, Bak-1, caspase-3 and p53). The results show that the mRNA expression of SelW were effectively increased after treatment with sodium selenite, and H 2O 2-induced cell apoptosis was significantly decreased and cell viability was significantly increased. 20 μM H 2O 2 was found to induce cell apoptosis and decrease cell viability, which was alleviated obviously when cells were pretreated with sodium selenite before exposure to 20 μM H 2O 2. Meanwhile, H 2O 2 induced a significantly up-regulation of the Bax/Bcl-2 ratio, Bax, Bak-1, caspase-3 and p53 and down-regulation of Bcl-2 ( P < 0.05). When lymphocytes were pretreated with Se before treated with H 2O 2, the Bax/Bcl-2 ratio and mRNA expression of those genes were significantly decreased, and Bcl-2 was increased ( P < 0.05). SelW siRNA-transfected cells were more sensitive to the oxidative stress induced by treatment of H 2O 2 than control cells. Silencing of the lymphocyte SelW gene decreased their cell viability, and increased their apoptosis rate and susceptibility to H 2O 2. Silencing of SelW significantly up-regulated the Bax/Bcl-2 ratio, Bax, Bak-1, caspase-3 and p53 and down-regulated Bcl-2 ( P < 0.05). The present study demonstrates that SelW plays an important role in protection of splenic lymphocyte of birds from oxidative stress. 相似文献
2.
BackgroundSelenoprotein W (SelW) was thought to play an antioxidant role in mammals. Because chicken SelW has no cysteine (Cys) at the residue 37 (Cys37) that is required for the presumed antioxidant function in mammals, this study was conducted to determine whether chicken SelW possessed the same function. MethodsSmall interfering RNAs (siRNAs) technology was applied to suppress the SelW expression in chicken embryonic myoblasts. Thereafter, these myoblasts were treated with different concentrations of H 2O 2 and assayed for cell viability, apoptosis rate, reactive oxygen species (ROS) status, and expression levels of apoptosis-related genes and proteins (Bax, Bcl-2, and caspase-3). ResultsSilencing of the myoblast SelW gene decreased their cell viability, and increased their apoptosis rate and susceptibility to H 2O 2. While the knockout down of SelW up-regulated Bax and caspase-3 and down-regulated Bcl-2, the induced oxidative injuries were alleviated by treatment with a ROS scavenger, N-acetyl-l-cysteine (NAC). ConclusionChicken SelW protected embryonic myoblasts against cell apoptosis mediated by endogenous and exogenous H 2O 2. General significanceChicken SelW possesses antioxidant function similar to the mammalian homologues despite the lack of Cys37 in the peptide. 相似文献
3.
Oxidative stress induces miR-200c, the predominant microRNA (miRNA) in lung tissues; however, the antioxidant role and biochemistry of such induction have not been clearly defined. Therefore, a lung adenocarcinoma cell line (A549) and a normal lung fibroblast (MRC-5) were used as models to determine the effects of miR-200c expression on lung antioxidant response. Hydrogen peroxide (H 2O 2) upregulated miR-200c, whose overexpression exacerbated the decrease in cell proliferation, retarded the progression of cells in the G2/M-phase, and increased oxidative stress upon H 2O 2 stimulation. The expression of three antioxidant proteins, superoxide dismutase (SOD)-2, haem oxygenase (HO)-1, and sirtuin (SIRT) 1, was reduced upon H 2O 2 stimulation in miR-200c-overexpressed A549 cells. This phenomenon of increased oxidative stress and antioxidant protein downregulation also occurs simultaneously in miR-200c overexpressed MRC-5 cells. Molecular analysis revealed that miR-200c inhibited the gene expression of HO-1 by directly targeting its 3′-untranslated region. The downregulation of SOD2 and SIRT1 by miR-200c was mediated through zinc finger E-box-binding homeobox 2 (ZEB2) and extracellular signal-regulated kinase 5 (ERK5) pathways, respectively, where knockdown of ZEB2 or ERK5 decreased the expression of SOD2 or SIRT1 in A549 cells. LNA anti-miR-200c transfection in A549 cells inhibited the endogenous miR-200c expression, resulting in increased expressions of antioxidant proteins, reduced oxidative stress and recovered cell proliferation upon H 2O 2 stimulation. These findings indicate that miR-200c fine-tuned the antioxidant response of the lung cells to oxidative stress through several pathways, and thus this study provides novel information concerning the role of miR-200c in modulating redox homeostasis of lung. 相似文献
4.
This study aimed to elucidate the effect of 6- n-propylthiouracil (PTU)-induced hypothyroidism on oxidative stress parameters and expression of antioxidant enzymes in cerebral cortex of rat brain during postnatal development. A significant decrease in levels of lipid peroxidation and H 2O 2 were seen in 7 and 30 days old PTU-treated rats with respect to their controls. Significantly decreased activities of superoxide dismutase (SOD) and catalase (CAT) along with the translated products of SOD1 and SOD2 were observed in 7, 15 and 30 days old PTU-treated rats as compared to their respective controls. However, increase in translated product of CAT was seen in all age groups of PTU-treated rats. Glutathione peroxidase activity was decreased in 7 days and increased in 15 days old PTU-treated rats with respect to their control groups. Histological sections clearly show a decline in neuronal migration with neurons packed together in the hypothyroid group as compared to the control. 相似文献
5.
Uric acid (UA) is a potent scavenger of oxidants in most mammalian and avian species. The aim of this study was to obtain more comprehensive information regarding the relationship between different concentrations of UA and oxidative balance in chicken cardiac cells. First, oxidative damage parameters were measured in chicken cardiac cells treated with different concentrations of UA. UA concentrations within the normal physiological range had no effect, while treatment with a high level of UA, i.e. 1200?μM, increased the malondialdehyde (MDA) and protein carbonyl contents, decreased the superoxide dismutase (SOD) and catalase (CAT) activities, and had no effect on glutathione (GSH) in cardiac muscle cells. In addition, the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway was stimulated in cells treated with 1200?μM UA. Next, the role of UA in protecting cells from oxidative damage was investigated in hydrogen peroxide (H 2O 2)-damaged chicken cardiac cells. Treatment with UA within the normal physiological range reduced the increased MDA and protein carbonyl contents and SOD enzymatic activity induced by H 2O 2 exposure to some extent and inhibited reactive oxygen species (ROS) formation, presumably as a result of the Nrf2 pathway activation in H 2O 2-damaged cells. By contrast, the MDA and protein carbonyl contents were increased, SOD enzymatic activity was depressed, and the Nrf2 pathway was further down-regulated in H 2O 2-damaged cells treated with 1200?μM UA. In conclusion, the results indicated that physiological UA concentration partially alleviated oxidative stress in chicken cardiac muscle cells treated with H 2O 2. However, supraphysiological UA concentrations promoted oxidative damages directly in primary cultured chicken cardiac muscle cells and aggravated oxidative stress in H 2O 2-damaged cells. 相似文献
6.
Oxidative stress has been shown to cause either apoptosis or stress-induced premature senescence (SIPS) in different cell types. At present, it is generally accepted that stem cells have high resistance to oxidative stress; however, data reported by various authors are disputed. In this study, we investigated stress responses of human embryonic stem cells (hESC) and human mesenchymal stem cells (hMESC) derived from desquamated endometrium to hydrogen peroxide (H 2O 2). Cell viability was evaluated by MTT assay. LD 50 were determined as 300–350, 370–400, and 600–700 μM for hESC, human embryonic fibroblasts, and hMESC, respectively. Thus, of the studied cell lines, hMESC exhibited the greatest resistance to increased H 2O 2 concentration. We found for the first time that a sublethal concentration of H 2O 2 induced premature senescence phenotype in hMESC, like in HEF, that was characterized by increased expression of cyclin-dependent kinase inhibitor p21 Waf1/Cip1, an irreversible cell cycle arrest, the permanent loss of proliferative potential, cell hypertrophy, and the SA-β-Gal staining. Whereas the sublethal H 2O 2 concentration (200 μM) promoted in hMESC only SIPS, higher H 2O 2 concentrations also induced apoptosis in a small part of the cell population. On the contrary, in hESC, H 2O 2, regardless of the tested concentrations (from 50 to 500 μM), triggered apoptosis, which was the only pronounced response of these cells to oxidative damage. The obtained data demonstrate that stem cells of different origins under conditions of oxidative stress use different protective mechanisms: hESC rapidly eliminate damaged cells through apoptosis, whereas hMESC are subjected to premature senescence. 相似文献
7.
Reactive oxygen species and oxidative stress are associated with neuronal cell death in many neurodegenerative conditions. However, the exact molecular mechanisms triggered by oxidative stress in neurodegeneration are still unclear. This study used the B65 rat neuroblastoma cell line as a model to study the molecular events that occur after H 2O 2 treatment. Treatment of B65 cells with H 2O 2 rapidly up-regulated the DNA damage pathway involved in double-strand breakage. Subsequently, proteins involved in p53 regulation, such as sirtuin 1 and STAT1, were modified. In addition, H 2O 2 treatment altered the pattern of cell cycle protein expression. Specifically, a decrease was found in the expression of cyclin D1, cdk4 and surprisingly the levels of cyclin A and the retinoblastoma protein phosphorylated at ser780 were increased. Furthermore, this study shows that pre-treatment of B65 cells with 50 µM trolox confers almost total protection against apoptotic cell death and restores the cell cycle. Likewise, the increase in retinoblastoma phosphorylation was attenuated by KU-55993, a selective ATM inhibitor, and also by trolox. These observations indicate that DNA damage and oxidative stress are responsible for cell cycle regulation. In summary, this study describes the molecular mechanisms involved in cell cycle alterations induced by oxidative stress in B65 cells. These findings highlight the relevance of ATM in the regulation of cell cycle after oxidative stress. 相似文献
8.
It is known that oxidative stress may cause neuronal injury and several experimental models showed that As2O3 exposure causes oxidative stress. Lycopene, a carotenoid, has been shown to have protective effect in neurological disease models due to antioxidant activity, but its effect on As2O3-induced neurotoxicity is not identified yet. The aim of this study is to investigate the effects of lycopene on As2O3-induced neuronal damage and the related mechanisms. Cell viability was determined by the MTT assay. Lycopene was administrated with different concentrations (2, 4, 6 and 8 µM) one hour before 2 µM As2O3 exposure in SH-SY5Y human neuroblastoma cells. The anti-oxidant effect of lycopene was determined by measuring superoxide dismutase (SOD), catalase (CAT) hydrogen peroxide (H2O2), malondialdehyde (MDA), total antioxidant status (TAS) and total oxidant status (TOS). MTT results and LDH cytotoxicity analyses showed that pretreatment with 8 µM lycopene significantly improved the toxicity due to As2O3 exposure in SH?SY5Y neuroblastoma cells. Pretreatment with lycopene significantly increased the activities of anti?oxidative enzymes as well as total antioxidant status and decreased total oxidative status in As2O3 exposed cells. The results of this study indicate that lycopene may be a potent neuroprotective against oxidative stress and could be used to prevent neuronal injury or death in several neurological diseases. 相似文献
9.
Ataxia telangiectasia (AT) is caused by mutational inactivation of the ataxia telangiectasia mutated ( Atm) gene, which is involved in DNA repair. Increased oxidative stress has been shown in human AT cells and neuronal tissues of Atm-deficient mice. Heme oxygenase-1 (HO-1) is an inducible antioxidant enzyme and protects cells against oxidative stress. The purpose of this study is to determine whether ATM induces antioxidant enzyme HO-1 and protects cells from oxidative stress-mediated apoptosis by driving the activation of PKC-δ and NF-κB, by increasing cell viability, and by downregulating DNA fragmentation and apoptotic indicators (apoptosis-inducing factor and cleaved caspase-3). AT fibroblasts stably transfected with human full-length ATM cDNA (YZ5 cells) or the empty vector (MOCK cells) were treated with H 2O 2 as a source of reactive oxygen species (ROS). As a result, transfection with ATM inhibited ROS-induced cell death and DNA fragmentation in MOCK cells. Transfection with ATM induced expression of HO-1 which was mediated by PKC-δ and NF-κB in H 2O 2-treated MOCK cells. ZnPP, an HO-1 inhibitor, and transfection with HO-1 siRNA increased ROS levels and apoptosis, whereas hemin, an HO-1 activator, reduced ROS levels and apoptosis in H 2O 2-treated YZ5 cells. Rottlerin, a PKC-δ inhibitor, inhibited NF-κB activation and HO-1 expression in H 2O 2-treated YZ5 cells. MOCK cells showed increased cell death, DNA fragmentation, and apoptotic indicators compared to YZ5 cells exposed to H 2O 2. In addition, transfection with p65 siRNA increased ROS levels and DNA fragmentation, but decreased HO-1 protein levels in H 2O 2-treated YZ5 cells. In conclusion, ATM induces HO-1 expression via activation of PKC-δ and NF-κB and inhibits oxidative stress-induced apoptosis. A loss of HO-1 induction may explain why AT patients are vulnerable to oxidative stress. 相似文献
10.
Oxidative stress can induce neuronal apoptosis via the production of superoxide and hydroxyl radicals. This process is as a major pathogenic mechanism in neurodegenerative disorders. In this study, we aimed to clarify whether theaflavins protect PC12 cells from oxidative stress damage induced by H 2O 2. A cell model of PC12 cells undergoing oxidative stress was created by exposing cells to 200 μM H 2O 2 in the presence or absence of varying concentrations of theaflavins (5, 10, and 20 μM). Cell viability was monitored using the MTT assay and Hoechst 33258 staining, showing that 10 μM theaflavins enhanced cell survival following 200 μM H 2O 2 induced toxicity and increased cell viability by approximately 40?%. Additionally, we measured levels of intracellular reactive oxygen species (ROS) and antioxidant enzyme activity. This suggested that the neuroprotective effect of theaflavins against oxidative stress in PC12 cells is derived from suppression of oxidant enzyme activity. Furthermore, Western blot analyses indicated that theaflavins downregulated the ratio of pro-apoptosis/anti-apoptosis proteins Bax/Bcl-2. Theaflavins also downregulated the expression of caspase-3 compared with a H 2O 2-treated group that had not been treated with theaflavins. Interestingly, this is the first study to report that the four main components of theaflavins found in black tea can protect neural cells (PC12) from apoptosis induced by H 2O 2. These findings provide the foundations for a new field of using theaflavins or its source, black tea, in the treatment of neurodegenerative diseases caused by oxidative stress. 相似文献
11.
Neurological diseases such as Alzheimer’s and Parkinson’s diseases are incurable progressive neurological disorders caused by the degeneration of neuronal cells and characterized by motor and non-motor symptoms. Curcumin, a turmeric product, is an anti-inflammatory agent and an effective reactive oxygen and nitrogen species scavenging molecule. Hydrogen peroxide (H 2O 2) is the main source of oxidative stress, which is claimed to be the major source of neurological disorders. Hence, in this study we aimed to investigate the effect of curcumin on Ca 2+ signaling, oxidative stress parameters, mitochondrial depolarization levels and caspase-3 and -9 activities that are induced by the H 2O 2 model of oxidative stress in SH-SY5Y neuronal cells. SH-SY5Y neuronal cells were divided into four groups namely, the control, curcumin, H 2O 2, and curcumin?+?H 2O 2 groups. The dose and duration of curcumin and H 2O 2 were determined from published data. The cells in the curcumin, H 2O 2, and curcumin?+?H 2O 2 groups were incubated for 24?h with 5?µM curcumin and 100?µM H 2O 2. Lipid peroxidation and cytosolic free Ca 2+ concentrations were higher in the H 2O 2 group than in the control group; however, their levels were lower in the curcumin and curcumin?+?H 2O 2 groups than in the H 2O 2 group alone. Reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) values were lower in the H 2O 2 group although they were higher in the curcumin and curcumin?+?H 2O 2 groups than in the H 2O 2 group. Caspase-3 activity was lower in the curcumin group than in the H 2O 2 group. In conclusion, curcumin strongly induced modulator effects on oxidative stress, intracellular Ca 2+ levels, and the caspase-3 and -9 values in an experimental oxidative stress model in SH-SY5Y cells. 相似文献
12.
Anthocyanins (AC) from Coreopsis tinctoria possesses strong antioxidant properties, while the effects of AC on cells damage induced by reactive oxygen species (ROS) in diabetes mellitus diseases progression have not been reported. The present study was carried out to evaluate the protective property of AC against cellular oxidative stress with an experimental model, H 2O 2‐exposed MIN6 cells. AC could reverse the decrease of cell viability induced by H 2O 2 and efficiently suppressed cellular ROS production and cell apoptosis. In addition, Real‐time PCR and Western blot analyses indicated that AC could protect MIN6 cells against oxidative injury through increasing the translocation of Nrf2 into nuclear, decreasing the phosphorylation level of p38 and up‐regulating the protein expression of antioxidant enzyme (SOD1, SOD2 and CAT). Thus, this study provides evidence to support the beneficial effect of AC in inhibiting MIN6 cells from H 2O 2‐induced oxidative injury. 相似文献
13.
Acanthamoeba castellanii ( A. castellanii) is an important opportunistic parasite. Induction of oxidative stress by the host immune system is one of the most important defense strategies against parasites. Hence, parasites partly deal with oxidative stress by different mechanisms. Identifying resistance mechanisms of A. castellanii parasites against oxidative stress is important to achieve a new therapeutic approach. Thus, this study aimed to understand the resistance mechanisms of A. castellanii, against oxidative stress. Trophozoites of A. castellanii were treated with different concentrations of H 2O 2. The half maximal inhibitory concentration (IC 50) of H 2O 2 was determined using the MTT assay. The induction of oxidative stress was confirmed by flow cytometer. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) were determined. The gene expression levels of CAT and SOD were measured by qRT-PCR. Furthermore, 3-amino-1:2:4-triazole (3-AT) and potassium cyanide (KCN) were used as specific inhibitors of CAT and SOD, respectively. Cell cycle assay and the apoptosis were evaluated by flow cytometer. The activities of SOD, CAT, GR, and GPx, showed an increase in oxidative stress. The cell cycle analysis revealed that most of the cellular population was in G0 and G1 phases. The apoptosis increased in oxidative stress conditions. Moreover, the apoptosis significantly increased after the specific inhibition of CAT and SOD under oxidative stress. The gene expression levels of CAT and SOD significantly increased under oxidative stress. A. castellanii can resist the host immune system through various mechanisms, including evoking its antioxidant enzymes. Therefore, by reducing or inhibiting the activity of the parasite's antioxidant enzymes such as SOD and CAT, it is possible to cope with A. castellanii. 相似文献
14.
Peroxiredoxins (Prxs) are ubiquitous thiol-specific antioxidant enzymes that are critically involved in cell defense and protect cells from oxidative damage. In this study, a putative Type II Prx (ThPrx1) was identified and characterized from Tamarix hispida. The expression of ThPrx1 is highly induced in response to hydrogen peroxide (H 2O 2) and methyl viologen (MV) stresses. When expressed ectopically, ThPrx1 showed enhanced tolerance against oxidative stress in yeast and Arabidopsis. In addition, transgenic Arabidopsis plants overexpressing ThPrx1 displayed improved seedling survival rates and increased root growth and fresh weight gain under H 2O 2 and MV treatments. Moreover, transgenic Arabidopsis plants showed decreased accumulation of H 2O 2, superoxide (O 2??) and malondialdehyde (MDA), increased superoxide dismutase (SOD) activity compared to wild-type (WT) plants under oxidative stress. Moreover, transgenic plants maintained higher photosynthesis efficiency and lower electrolyte leakage rates than that of WT plants under stress conditions. These results clearly indicated that ThPrx1 plays an important role in cellular redox homeostasis under stress conditions, leading to the maintenance of membrane integrity and increased tolerance to oxidative stress. 相似文献
15.
Potamogeton crispus L. ( P. crispus) is the type of a widely distributed perennial herbs, which is rich in rhodoxanthin. In this research work, five antioxidant indexes in vitro were selected to study the antioxidant activity of rhodoxanthin from P. crispus (RPC). A model of hydrogen peroxide (H 2O 2) -induced oxidative damage in RAW264.7 cells was established to analyze the antioxidant effect and potential mechanism of RPC. The levels of ROS, MDA and the activities of oxidation related enzymes by H 2O 2 were determined by enzyme linked immunosorbent assay (ELISA). The mRNA expression of Nrf-2, HO-1, SOD1 and SOD2 was measured by qRT-PCR assay. According to the results, RPC had free radical scavenging ability for 2, 2-diphenyl-1-trinitrohydrazine (DPPH), 2,2’-azinobis(3-ethylbenzo-thiazoline-6-sulfonic acid radical ion) (ABTS), hydroxyl radical and superoxide anion. RPC significantly decreased the level of MDA and ROS and LDH activity, while increased GSH level and activities of SOD, GSH−Px and CAT. It was showed that RPC could increase the mRNA expression of Nrf-2, HO-1, SOD1 and SOD2 in RAW264.7 cells in a dose-dependently manner. In summary, RPC treatment could effectively attenuate the H 2O 2-induced cell damage rate, and the mechanism is related to the reduction of H 2O 2 induced oxidative stress and the activation of Nrf-2 pathway. 相似文献
16.
Photoreceptor degeneration (PD) refers to a group of heterogeneous outer retinal dystrophies characterized by the death of photoreceptors. Both oxidative stress and inflammation are involved in the pathogenesis of PD. We investigate whether vitamin D has a potential for the treatment of PD by evaluating the anti‐oxidative stress and anti‐inflammatory properties of the active form of vitamin D 3, 1,α, 25‐dihydroxyvitamin D 3, in a mouse cone cell line, 661W. Mouse cone cells were treated with H 2O 2 or a mixture of H 2O 2 and vitamin D; cell viability was determined. The production of reactive oxygen species (ROS) in treated and untreated cells was measured. The expression of key anti‐oxidative stress and inflammatory genes in treated and untreated cells was determined. Treatment with vitamin D significantly increased cell viability and decreased ROS production in 661W cells under oxidative stress induced by H 2O 2. H 2O 2 treatment in 661W cells can significantly down‐regulate the expression of antioxidant genes and up‐regulate the expression of neurotoxic cytokines. Vitamin D treatment significantly reversed these effects and restored the expression of antioxidant genes. Vitamin D treatment also can block H 2O 2 induced oxidative damages. The data suggested that vitamin D may offer a therapeutic potential for patients with PD. 相似文献
17.
Human mesenchymal stem cells are a promising cell source for tissue engineering. During transplantation, they may be subjected to oxidative stress due to unfavorable cellular microenvironment characterized by an increased level of reactive oxygen species. Recently, we have demonstrated that oxidative stress response of human mesenchymal stem cells derived from endometrium (hMESCs) depends on the oxidizer concentration. The duration of cell treatment with an oxidizer also may play an important role. In this study, we investigated the dependence of the cell response on H 2O 2 treatment duration. The effects of high H 2O 2 doses on hMESCs and human lung embryonic fibroblasts were compared. In both cell types, H 2O 2 treatment for 60 min caused multiphase cell cycle arrest, with dose-dependent cell death occurring equally in all phases of the cell cycle. However, the cell death dynamics in hMESCs and fibroblasts were different. Interestingly, in both cell types, shortening of H 2O 2 treatment from 60 to 10 min induced growth retardation, G1-phase cell accumulation, and cell size increase. Collectively, these findings suggest that there is induction of premature senescence. Thus, shortening of oxidative stress induced in human endometrial stem cells and embryonic fibroblasts by high H 2O 2 doses enables one to modulate cellular response as both cell death and premature senescence. 相似文献
18.
We previously reported that autophagy is upregulated in Prnp-deficient ( Prnp0/0) hippocampal neuronal cells in comparison to cellular prion protein (PrP C)-expressing ( Prnp+/+) control cells under conditions of serum deprivation. In this study, we determined whether a protective mechanism of PrP C is associated with autophagy using Prnp0/0 hippocampal neuronal cells under hydrogen peroxide (H 2O 2)-induced oxidative stress. We found that Prnp0/0 cells were more susceptible to oxidative stress than Prnp+/+ cells in a dose- and time-dependent manner. In addition, we observed enhanced autophagy by immunoblotting, which detected the conversion of microtubule-associated protein 1 light chain 3 β (LC3B)-I to LC3B-II, and we observed increased punctate LC3B immunostaining in H 2O 2-treated Prnp0/0 cells compared with H 2O 2-treated control cells. Interestingly, this enhanced autophagy was due to impaired autophagic flux in the H 2O 2-treated Prnp0/0 cells, while the H 2O 2-treated Prnp+/+ cells showed enhanced autophagic flux. Furthermore, caspase-dependent and independent apoptosis was observed when both cell lines were exposed to H 2O 2. Moreover, the inhibition of autophagosome formation by Atg7 siRNA revealed that increased autophagic flux in Prnp+/+ cells contributes to the prosurvival effect of autophagy against H 2O 2 cytotoxicity. Taken together, our results provide the first experimental evidence that the deficiency of PrP C may impair autophagic flux via H 2O 2-induced oxidative stress. 相似文献
20.
Oxidative stress is recognized as one of the pathogenic mechanisms involved in neurodegenerative disease. However, recent evidence has suggested that regulation of cellular fate in response to oxidative stress appears to be dependent on the stress levels. In this study, using HT22 cells, we attempted to understand how an alteration in the oxidative stress levels would influence neuronal cell fate. HT22 cell viability was reduced with exposure to high levels of oxidative stress, whereas, low levels of oxidative stress promoted cell survival. Erk1/2 activation induced by a low level of oxidative stress played a role in this cell protective effect. Intriguingly, subtoxic level of H 2O 2 induced expression of a growth factor, progranulin (PGRN), and exogenous PGRN pretreatment attenuated HT22 cell death induced by high concentrations of H 2O 2 in Erk1/2-dependent manner. Together, our study indicates that two different cell protection mechanisms are activated by differing levels of oxidative stress in HT22 cells. 相似文献
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