共查询到20条相似文献,搜索用时 33 毫秒
1.
Transient Receptor Potential (TRP) channels are mostly Ca 2+ permeable cation channels. Transient Receptor Potential Melastatin-like 2 (TRPM2) is expressed in neurological tissues such as brain, dorsal root ganglia (DRG) neurons, hippocampus and also liver, heart and kidney. The SH-SY5Y cells are mostly used as a cellular model of neurodegenerative diseases, Alzheimer's and Parkinson's diseases. Curcumin, shows phenolic structure, synthesized by Curcuma longa L. (turmeric), has powerful non-enzymatically antioxidant effects compared with Vitamin E. Hence, we aimed to investigate that effects of curcumin on TRPM2 cation channel currents using the whole-cell Patch-Clamp method, Ca 2+ signaling, apoptosis and cell viability (MTT) assays, reactive oxygen species (ROS) production, mitochondrial membrane potential levels, caspase 3 and caspase 9 activities in TRPM2 transfected SH-SY5Y neuroblastoma cells. For this aim, we designed four experimental groups named; control, curcumin, transfected and transfected?+?curcumin groups. Cytosolic free calcium concentrations were higher in transfected group compared with curcumin and transfected?+?curcumin group. Moreover, these data examined with whole-cell Patch-Clamp recordings of single cells in all groups. ROS levels were significantly higher in transfected group than in transfected?+?curcumin group. Apoptosis levels in transfected?+?curcumin group were lower than in transfected group. Procaspase 9 and procaspase 3 levels measured by western blotting and caspase 3 and caspase 9 levels by spectrophotometric methods show that TRPM2 transfected cells are more tended to apoptosis. In conclusion, curcumin strongly induces modulator effects on TRPM2-mediated Ca 2+ influx caused by ROS and caspase 3 and 9 processes in SH-SY5Y neuroblastoma cells. 相似文献
2.
AbstractExogenous hydrogen peroxide (H 2O 2) can easily penetrate into biological membranes and enhance the formation of other reactive oxygen species (ROS). In the present study, we have investigated the neuroprotective effects of insulin on H 2O 2-induced toxicity of retinoic acid (RA)-differentiated SH-SY5Y cells. To measure the changes in the cell viability of SH-SY5Y cells at different concentrations of H 2O 2 for 24?h, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT)-based assay was used and a 100?µM H 2O 2 was selected to establish a model of H 2O 2-induced oxidative stress. Further assays showed that 24?h of 100?µM H 2O 2-induced significant changes in the levels of lactate dehydrogenase (LDH), nitric oxide (NO), ROS, and calcium ion (Ca 2+) in neuronal cells, but insulin can effectively diminish the H 2O 2-induced oxidative damages to these cells. Moreover, cells treated with insulin increased H 2O 2-induced suppression of glutathione levels and exerted an apparent suppressive effect on oxidative products. The results of insulin treatment with SH-SY5Y cells increased the Bcl-2 levels and decreased the Akt levels. The treatment of insulin had played a protective effect on H 2O 2-induced oxidative stress related to the Akt/Bcl-2 pathways. 相似文献
3.
Oxidative stress-induced neuronal apoptosis plays an important role in many neurodegenerative disorders. In this study, we have shown that indirubin-3-oxime, a derivative of indirubin originally designed for leukemia therapy, could prevent hydrogen peroxide (H 2O 2)-induced apoptosis in both SH-SY5Y cells and primary cerebellar granule neurons. H 2O 2 exposure led to the increased activities of glycogen synthase kinase 3β (GSK3β) and extracellular signal-regulated kinase (ERK) in SH-SY5Y cells. Indirubin-3-oxime treatment significantly reversed the altered activity of both the PI3-K/Akt/GSK3β cascade and the ERK pathway induced by H 2O 2. In addition, both GSK3β and mitogen-activated protein kinase inhibitors significantly prevented H 2O 2-induced neuronal apoptosis. Moreover, specific inhibitors of the phosphoinositide 3-kinase (PI3-K) abolished the neuroprotective effects of indirubin-3-oxime against H 2O 2-induced neuronal apoptosis. These results strongly suggest that indirubin-3-oxime prevents H 2O 2-induced apoptosis via concurrent inhibiting GSK3β and the ERK pathway in SH-SY5Y cells, providing support for the use of indirubin-3-oxime to treat neurodegenerative disorders caused or exacerbated by oxidative stress. 相似文献
4.
Many lines of evidence suggest that microgravity results in increased oxidative stress in the nervous system. In order to
protect neuronal cells from oxidative damage induced by microgravity, we selected some flavonoids that might prevent oxidative
stress because of their antioxidant activities. Among the 20 flavonoids we examined, we found that isorhamnetin and luteolin
had the best protective effects against H 2O 2 or SIN-1-induced cytotoxicity in SH-SY5Y cells. Using a clinostat to simulate microgravity, we found that isorhamnetin and
luteolin treatment protected SH-SY5Y cells by preventing microgravity-induced increases in reactive oxygen species (ROS),
nitric oxide (NO) and 3-nitrotyrosine (3-NT) levels, and a decrease in antioxidant power (AP). Moreover, isorhamnetin and
luteolin treatment downregulated the expression of inducible nitric oxide synthase (iNOS), and oxidative stress was significantly
inhibited by an iNOS inhibitor in SH-SY5Y cells exposed to simulated microgravity (SMG). These results indicate that isorhamnetin
and luteolin could protect against microgravity-induced oxidative stress in neuroblastoma SH-SY5Y cells by inhibiting the
ROS-NO pathway. These two flavonoids may have potential for preventing oxidative stress induced by space flight or microgravity. 相似文献
5.
Oxidative stress is an established event in the pathology of neurobiological diseases. Previous studies indicated that store-operated Ca 2+ entry (SOCE) has been involved in oxidative stress. The present study was carried out to investigate the effects of SOCE inhibition on neuronal oxidative stress injury induced by hydrogen peroxide (H 2O 2) in HT22 cells, a murine hippocampal neuronal model. H 2O 2 insult induced significant intracellular Ca 2+ overload, mitochondrial dysfunction and cell viability decrease. Inhibition of SOCE by pharmacological inhibitor and STIM1 RNAi significantly alleviated intracellular Ca 2+ overload, restored the mitochondrial membrane potential (MMP), decreased cytochrome C release and eventually inhibited H 2O 2-induced cell apoptosis. These findings suggest that SOCE inhibition exhibited neuroprotection against oxidative stress induced by H 2O 2 and SOCE might be a useful therapeutic target in neurobiological disorders. 相似文献
6.
Increasing evidence suggests that Alzheimer’s disease is associated with mitochondrial dysfunction and oxidative damage. To
develop a cellular model of Alzheimer’s disease, we investigated the effects of thioredoxin (Trx) expression in the response
to mitochondrial dysfunction-enhanced oxidative stress in the SH-SY5Y human neuroblastoma cells. Treatment of SH-SY5Y cells
with 15 mM of NaN 3, an inhibitor of cytochrome c oxidase (complex IV), led to alteration of mitochondrial membrane potential but no significant changes in cell viability.
Therefore, cells were first treated with 15 mM NaN 3 to induce mitochondrial dysfunction, then, exposed to different concentrations of H 2O 2. Cell susceptibility was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and morphological
observation. Expressions of Trx mRNA and protein were determined by RT-PCR; and Western-blot analysis, respectively. It was
found that the SH-SY5Y cells with mitochondrial impairment had lower levels of Trx mRNA and protein, and were significantly
more vulnerable than the normal cells after exposure to H 2O 2 while no significant changes of Trx mRNA and protein in SH-SY5Y cells exposed to H 2O 2 but without mitochondrial complex IV inhibition. These results, together with our previous study in primary cultured neurons,
demonstrated that the increased susceptibility to oxidative stress is induced at least in part by the down-regulation of Trx
in SH-SY5Y human neuroblastoma cells with mitochondrial impairment and also suggest the mitochondrial dysfunction-enhanced
oxidative stress could be used as a cellular model to study the mechanisms of Alzheimer’s disease and agents for prevention
and treatment. 相似文献
7.
It has been widely suggested that selenium (Se) deficiency play an important role in the pathophysiology of epilepsy. It has been reported that Se provides protection against the neuronal damage in patients and animals with epilepsy by restoring the antioxidant defense mechanism. The neuroprotective effects of topiramate (TPM) have been reported in several studies but the putative mechanism of action remains elusive. We investigated effects of Se and TPM in neuronal PC12 cell by evaluating Ca 2+ mobilization, lipid peroxidation and antioxidant levels. PC12 cells were divided into eight groups namely control, TPM, Se, H 2O 2, TPM + H 2O 2, Se + H 2O 2, Se + TPM and Se + TPM + H 2O 2. The toxic doses and times of H 2O 2, TPM and Se were determined by cell viability assay which is used to evaluate cell viability. Cells were incubated with 0.01 mM TPM for 5 h and 500 nM Se for 10 h. Then, the cells were exposed to 0.1 mM H 2O 2 for 10 h before analysis. The cells in all groups except control, TPM and Se were exposed to H 2O 2 for 15 min before analysis. Cytosolic Ca 2+ release and lipid peroxidation levels were higher in H 2O 2 group than in control, Se and TPM combination groups although their levels were decreased by incubation of Se and TPM combination. However, there is no difference on Ca 2+ release in TPM group. Glutathione peroxidase activity, reduced glutathione and vitamin C levels in the cells were lower in H 2O 2 group than in control, Se and TPM groups although their values were higher in the cells incubated with Se and TPM groups than in H 2O 2 groups. In conclusion, these results indicate that Se induced protective effects on oxidative stress in PC12 cells by modulating cytosolic Ca 2+ influx and antioxidant levels. TPM modulated also lipid peroxidation and glutathione and vitamin C concentrations in the cell system. 相似文献
8.
The Na+ and Ca 2+-permeable melastatin related transient receptor potential 2 (TRPM2) channels can be gated either by ADP-ribose (ADPR) in
concert with Ca 2+ or by hydrogen peroxide (H 2O 2), an experimental model for oxidative stress, binding to the channel’s enzymatic Nudix domain. Since the mechanisms that
lead to TRPM2 gating in response to ADPR and H 2O 2 are not understood in neuronal cells, I summarized previous findings and important recent advances in the understanding of
Ca 2+ influx via TRPM2 channels in different neuronal cell types and disease processes. Considering that TRPM2 is activated by
oxidative stress, mediated cell death and inflammation, and is highly expressed in brain, the channel has been investigated
in the context of central nervous system. TRPM2 plays a role in H 2O 2 and amyloid β-peptide induced striatal cell death. Genetic variants of the TRPM2 gene confer a risk of developing Western
Pacific amyotropic lateral sclerosis and parkinsonism-dementia complex and bipolar disorders. TRPM2 also contributes to traumatic
brain injury processes such as oxidative stress, inflammation and neuronal death. There are a limited number of TRPM2 channel
blockers and they seem to be cell specific. For example, ADPR-induced Ca 2+ influx in rat hippocampal cells was not blocked by N-(p-amylcinnomoyl)anthralic acid (ACA), the IP 3 receptor inhibitor 2-aminoethoxydiphenyl borate or PLC inhibitor flufenamic acid (FFA). However, the Ca 2+ entry in rat primary striatal cells was blocked by ACA and FFA. In conclusion TRPM2 channels in neuronal cells can be gated
by either ADPR or H 2O 2. It seems to that the exact relationship between TRPM2 channels activation and neuronal cell death still remains to be determined. 相似文献
9.
BackgroundWhen redox balance is lost in the brain, oxidative stress can cause serious damage that leads to neuronal loss, in congruence with neurodegenerative diseases. Aucubin (AU) is an iridoid glycoside and that is one of the active constituents of Eucommia ulmoides, has many pharmacological effects such as anti-inflammation, anti-liver fibrosis, and anti-atherosclerosis. PurposeThe present study aimed to evaluate the inhibitory effects of AU on cell oxidative stress against hydrogen peroxide (H 2O 2)-induced injury in SH-SY5Y cells in vitro. MethodsSH-SY5Y cells were simultaneously treated with AU and H 2O 2 for 24 h. Cell viability was measured by CCK-8. Additionally, mitochondrial membrane depolarization, reactive oxygen species (ROS) generation, and cell apoptosis were measured by flow cytometry. ResultsThe results showed that AU can significantly increase the H 2O 2-induced cell viability and the mitochondrial membrane potential, decrease the ROS generation, malondialdehyde (MDA), and increase glutathione (GSH) contents and the superoxide dismutase (SOD) activity. We also found that H 2O 2 stimulated the production of nitric oxide (NO), which could be reduced by treatment with AU through inhibiting the inducible nitric oxide synthase (iNOS) protein expression. In H 2O 2-induced SH-SY5Y cells, the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) content and cell apoptosis were significantly reduced by AU treatment through nuclear factor E2-related factor 2/hemo oxygenase-1 (Nrf2/HO-1) activation, inhibiting the expression of p-NF-κB/NF-κB and down-regulating MAPK and Bcl-2/Bax pathways. ConclusionThese results indicate that AU can reduce inflammation and oxidative stress through the NF-κB, Nrf2/HO-1, and MAPK pathways. 相似文献
10.
Oxidative stress is involved in the development of aging-related diseases, such as neurodegenerative diseases. Dietary antioxidants that can protect neuronal cells from oxidative damage play an important role in preventing such diseases. Previously, we reported that water-soluble fractions purified from defatted sesame seed flour exhibit good antioxidant activity in vitro. In the present study, we investigated the protective effects of white and gold sesame seed water-soluble fractions (WS-wsf and GS-wsf, respectively) against 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH) and hydrogen peroxide (H 2O 2) induced oxidative stress in human neuroblast SH-SY5Y cells. Pretreatment with WS-wsf and GS-wsf did not protect cells against AAPH-induced cytotoxicity, while simultaneous co-treatment with AAPH significantly improved cell viability and inhibited membrane lipid peroxidation. These results suggest that WS-wsf and GS-wsf protect cells from AAPH-induced extracellular oxidative damage via direct scavenging of peroxyl radicals. When oxidative stress was induced by H 2O 2, pretreatment WS-wsf and GS-wsf significantly enhanced cell viability. These results suggest that in addition to radical scavenging, WS-wsf and GS-wsf enhance cellular resistance to intracellular oxidative stress by activation of the Nrf-2/ARE pathway as confirmed by the increased Nrf2 protein level in the nucleus and increased heme oxygenase 1 (HO-1) mRNA expression. The roles of ferulic and vanillic acids as bioactive antioxidants in these fractions were also confirmed. In conclusion, our results indicated that WS-wsf and GS-wsf, which showed antioxidant activity in vitro, are also efficient antioxidants in a cell system protecting SH-SY5Y cells against both extracellular and intracellular oxidative stress. 相似文献
11.
The present work was conducted to investigate the antioxidant activity and neuroprotective effects of Tripterygium regelii extract (TRE) on H 2O 2-induced apoptosis in human dopaminergic cells, SH-SY5Y. TRE possessed considerable amounts of phenolics (282.73 mg tannic
acid equivalents/g of extract) and flavonoids (101.43 mg naringin equivalents/g of extract). IC 50 values for reducing power and DPPH radical scavenging activity were 52.51 and 47.83 μg, respectively. The H 2O 2 scavenging capacity of TRE was found to be 57.68 μM × μg −1 min −1. By examining the effects of TRE on SH-SY5Y cells injured by H 2O 2, we found that after incubation of cells with TRE prior to H 2O 2 exposure, the H 2O 2 induced cytotoxicity was significantly reversed and the apoptotic features such as change in cellular morphology, nuclear
condensation and DNA fragmentation was inhibited. Moreover, TRE was very effective attenuating the disruption of mitochondrial
membrane potential and apoptotic cell death induced by H 2O 2. TRE extract effectively suppressed the up-regulation of Bax, Caspase-3 and -9, and down-regulation of Bcl-2. Moreover, TRE
pretreatment evidently increased the tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF) in SH-SY5Y cells.
These findings demonstrate that TRE protects SH-SY5Y cells against H 2O 2-induced injury and antioxidant properties may account for its neuroprotective actions and suggest that TRE might potentially
serve as an agent for prevention of neurodegenerative disease associated with oxidative stress. 相似文献
12.
An increase in oxidative stress is a key factor responsible for neurotoxicity induction and cell death leading to neurodegenerative diseases including Parkinson’s and Alzheimer’s diseases. Plant phenolics exert diverse bioactivities i.e., antioxidant, anti-inflammatory, and neuroprotective effects. Herein, phenolic compounds, namely protocatechuic aldehyde (PCA) constituents of Hydnophytum formicarum Jack. including vanillic acid (VA) and trans-ferulic acid (FA) found in Spilanthes acmella Murr., were explored for anti-neurodegenerative properties using an in vitro model of oxidative stress-induced neuroblastoma SH-SY5Y cells. Exposure of the neuronal cells with H 2O 2 resulted in the decrease of cell viability, but increasing in the level of reactive oxygen species (ROS) together with morphological changes and inducing cellular apoptosis. SH-SY5Y cells pretreated with 5 µM of PCA, VA, and FA were able to attenuate cell death caused by H 2O 2-induced toxicity, as well as decreased ROS level and apoptotic cells after 24 h of treatment. Pretreated SH-SY5Y cells with phenolic compounds also helped to upregulate H 2O 2-induced depletion of the expressions of sirtuin-1 (SIRT1) and forkhead box O (FoxO) 3a as well as induce the levels of antioxidant (superoxide dismutase (SOD) 2 and catalase) and antiapoptotic B-cell lymphoma 2 (Bcl-2) proteins. The findings suggest that these phenolics might be promising compounds against neurodegeneration. 相似文献
13.
Hydrogen peroxide (H 2O 2) is a major Reactive Oxygen Species (ROS), which has been implicated in many neurodegenerative conditions including Parkinson’s
disease (PD). Rosmarinus officinalis ( R. officinalis) has been reported to have various pharmacological properties including anti-oxidant activity. In this study, we investigated
the neuroprotective effects of R. officinalis extract on H 2O 2-induced apoptosis in human dopaminergic cells, SH-SY5Y. Our results showed that H 2O 2-induced cytotoxicity in SH-SY5Y cells was suppressed by treatment with R. officinalis. Moreover, R. officinalis was very effective in attenuating the disruption of mitochondrial membrane potential and apoptotic cell death induced by
H 2O 2. R. officinalis extract effectively suppressed the up-regulation of Bax, Bak, Caspase-3 and -9, and down-regulation of Bcl-2. Pretreatment
with R. officinalis significantly attenuated the down-regulation of tyrosine hydroxylase (TH), and aromatic amino acid decarboxylase (AADC) gene
in SH-SY5Y cells. These findings indicate that R. officinalis is able to protect the neuronal cells against H 2O 2-induced injury and suggest that R. officinalis might potentially serve as an agent for prevention of several human neurodegenerative diseases caused by oxidative stress
and apoptosis. 相似文献
14.
N 6-(4-hydroxybenzyl) adenine riboside (NHBA), isolated from Gastrodia elata Blume, has been demonstrated to show great pharmacological effects. The present study aimed to synthesize and identify the metabolites of NHBA, and to determine their neuroprotective potentials in vitro. After incubation with rat liver microsomes in the presence of NADPH, two metabolites were detected, which were further semisynthesized and identified as N 6-(4-hydroxylbenzyl) purine (NHBP) and N 6-(3,4-dihydroxylbenzyl) adenine riboside (ONHBA) by UPLC-QTOF-MS, 1H NMR and 13C NMR. Furthermore, the neuroprotective activities of NHBA and two metabolites were evaluated in SH-SY5Y cells. Our results demonstrated that NHBA substantially protected against H 2O 2-induced neuronal death in SH-SY5Y cells. Moreover, both ONHBA and NHBP could significantly prevent Aβ oligomers- and H 2O 2-induced neuronal death in SH-SY5Y cells. These results suggested that NHBA and its metabolites, ONHBA and NHBP, might be suitable for the development of new drugs in the treatment of neurodegenerative diseases, including Alzheimer’s disease in particular. 相似文献
15.
Iron accumulation and oxidative stress are associated with neurodegenerative disease. Labile iron is known to catalyze free radical generation and subsequent neuronal damage, whereas the role of oxidative stress in neuronal iron accumulation is less well understood. Here, we examined the effect of hydrogen peroxide (H 2O 2) treatment on cellular iron-uptake, -storage, and -release proteins in the neuroblastoma cell line SH-SY5Y. We found no detectable change in the iron-uptake proteins transferrin receptor-1 and divalent metal ion transporter. In contrast, H 2O 2 treatment resulted in significant degradation of the iron-exporter ferroportin (Fpn). A decrease in Fpn is expected to increase the labile iron pool (LIP), reducing the iron-regulatory protein (IRP)–iron-responsive element interaction and increasing the expression of ferritin-H (Ft-H) for iron storage. Instead, we detected IRP1 activation, presumably due to oxidative stress, and a decrease in Ft-H translation. A reduction in Ft-H mRNA was also observed, probably dependent on an antioxidant-response element present in the Ft-H enhancer. The decrease in Fpn and Ft-H upon H 2O 2 treatment led to a time-dependent increase in the cellular LIP. Our study reveals a complex regulation of neuronal iron-release and iron-storage components in response to H 2O 2 that may explain iron accumulation detected in neurodegenerative diseases associated with oxidative stress. 相似文献
16.
Oxidative stress is a critical route of damage in various psychological disorders such as schizophrenia, although fish oil
and risperidone (RISP) induce antioxidant effects in the human body. However, the mechanisms behind these effects remain elusive.
We investigated the effects of fish oil and RISP in the PC12 cell line by evaluating Ca 2+ mobilization, lipid peroxidation (LP) and antioxidant levels. PC12 cells were divided into eight flasks: control, fish oil,
RISP, H 2O 2, fish oil + H 2O 2, RISP + H 2O 2, fish oil + RISP and fish oil + RISP + H 2O 2. Cells were incubated with fish oil and RISP for 24 and 48 h, respectively. Then, cells were exposed to H 2O 2 for 15 min before analysis. Ca 2+ release and LP levels were higher in the H 2O 2 group than in the control, RISP and fish oil groups, although their levels were decreased by incubation of cells in fish
oil and RISP. Glutathione peroxidase activity, reduced glutathione and vitamin C levels in the cells were lower in the H 2O 2 group than in the control, RISP and fish oil groups, although levels were higher in cells incubated with fish oil and RISP
than in those in the H 2O 2 groups. In conclusion, these results indicate that RISP and fish oil induced protective effects on oxidative stress in PC12
cells by modulating cytosolic Ca 2+ release and antioxidant levels. 相似文献
17.
The transient receptor potential (TRP) protein superfamily is a diverse group of voltage-independent calcium-permeable cation
channels expressed in mammalian cells. These channels have been divided into six subfamilies, and two of them, TRPC and TRPM,
have members that are widely expressed and activated by oxidative stress. TRPC3 and TRPC4 are activated by oxidants, which
induce Na + and Ca 2+ entry into cells through mechanisms that are dependent on phospholipase C. TRPM2 is activated by oxidative stress or TNFα,
and the mechanism involves production of ADP-ribose, which binds to an ADP-ribose binding cleft in the TRPM2 C-terminus. Treatment
of HEK 293T cells expressing TRPM2 with H 2O 2 resulted in Ca 2+ influx and increased susceptibility to cell death, whereas coexpression of the dominant negative isoform TRPM2-S suppressed
H 2O 2-induced Ca 2+ influx, the increase in [Ca 2+] i, and onset of apoptosis. U937-ecoR monocytic cells expressing increased levels of TRPM2 also exhibited significantly increased
[Ca 2+] i and increased apoptosis after treatment with H 2O 2 or TNFα. A dramatic increase in caspase 8, 9, 3, 7, and PARP cleavage was observed in TRPM2-expressing cells, demonstrating
a downstream mechanism through which cell death is mediated. Inhibition of endogenous TRPM2 function through three approaches,
depletion of TRPM2 by RNA interference, blockade of the increase in [Ca 2+] i through TRPM2 by calcium chelation, or expression of the dominant negative splice variant TRPM2-S protected cell viability.
H 2O 2 and amyloid β-peptide also induced cell death in primary cultures of rat striatal cells, which endogenously express TRPM2.
TRPM7 is activated by reactive oxygen species/nitrogen species, resulting in cation conductance and anoxic neuronal cell death,
which is rescued by suppression of TRPM7 expression. TRPM2 and TRPM7 channels are physiologically important in oxidative stress-induced
cell death. 相似文献
18.
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
19.
The role of the kinase ataxia-telangiectasia mutated (ATM), a well-known protein engaged in DNA damage repair, in the regulation of neuronal responses to oxidative stress remains unexplored. Thus, the neuroprotective efficacy of KU-55933, a potent inhibitor of ATM, against cell damage evoked by oxidative stress (hydrogen peroxide, H 2O 2) has been studied in human neuroblastoma SH-SY5Y cells and compared with the efficacy of this agent in models of doxorubicin (Dox)- and staurosporine (St)-evoked cell death. KU-55933 inhibited the cell death induced by H 2O 2 or Dox but not by St in undifferentiated (UN-) and retinoic acid-differentiated (RA)-SH-SY5Y cells, with a more pronounced effect in the latter cell phenotype. Furthermore, this ATM inhibitor attenuated the Dox- but not H 2O 2-induced caspase-3 activity in both UN- and RA-SH-SY5Y cells. Although KU-55933 inhibited the H 2O 2- and Dox-induced activation of ATM, it attenuated the toxin-induced phosphorylation of the proteins H2AX and p53 only in the latter model of cell damage. Moreover, the ATM inhibitor prevented the H 2O 2-evoked increases in calpain and cathepsin D activity and attenuated cell damage to a similar degree as inhibitors of calpain (MDL28170) and cathepsin D (pepstatin A). Finally, we confirmed the neuroprotective potential of KU-55933 against the H 2O 2- and Dox-evoked cell damage in primary mouse cerebellar granule cells and in the mouse hippocampal HT-22 cell line. Altogether, our results extend the neuroprotective portfolio of KU-55933 to a model of oxidative stress, with this effect not involving inhibition of the γH2AX/p-p53/caspase-3 pathway and instead associated with the attenuation of calpain and cathepsin D activity. 相似文献
20.
Propofol (2,6-diisopropylphenol) is a widely used general anesthetic with anti-oxidant activities. This study aims to investigate protective capacity of propofol against hydrogen peroxide (H 2O 2)-induced oxidative injury in neural cells and whether the anti-oxidative effects of propofol occur through a mechanism involving the modulation of NADPH oxidase (NOX) in a manner of calcium-dependent. The rat differentiated PC12 cell was subjected to H 2O 2 exposure for 24 h to mimic a neuronal in vitro model of oxidative injury. Our data demonstrated that pretreatment of PC12 cells with propofol significantly reversed the H 2O 2-induced decrease in cell viability, prevented H 2O 2-induced morphological changes, and reduced the ratio of apoptotic cells. We further found that propofol attenuated the accumulation of malondialdehyde (biomarker of oxidative stress), counteracted the overexpression of NOX core subunit gp91 phox (NOX2) as well as the NOX activity following H 2O 2 exposure in PC12 cells. In addition, blocking of L-type Ca 2+ channels with nimodipine reduced H 2O 2-induced overexpression of NOX2 and caspase-3 activation in PC12 cells. Moreover, NOX inhibitor apocynin alone or plus propofol neither induces a significant downregulation of NOX activity nor increases cell viability compared with propofol alone in the PC12 cells exposed to H 2O 2. These results demonstrate that the protective effects of propofol against oxidative injury in PC12 cells are mediated, at least in part, through inhibition of Ca 2+-dependent NADPH oxidase. 相似文献
|