scholarly journals TrxR2 overexpression alleviates inflammation-mediated neuronal death via reducing the oxidative stress and activating the Akt–Parkin pathway

2019 ◽  
Vol 8 (5) ◽  
pp. 641-653 ◽  
Author(s):  
Jinbao Gao ◽  
Yunjun Li ◽  
Wende Li ◽  
Haijiang Wang
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cell Viability ◽  
Western Blotting ◽  
Neuronal Death ◽  
Protective Effects ◽  
Mitochondrial Apoptosis ◽  
Inflammation Response ◽  
N2a Cells

Abstract Neuronal death caused by inflammatory cytokine-mediated neuroinflammation is being extensively explored. Thioredoxin reductase (TrxR) 2 is a novel mediator of inflammation response. In the current study, we focus on the mechanisms of TrxR2 overexpression in inflammation-mediated neuronal death. LPS was used to induce neuroinflammation in N2a cells in vitro. Adenovirus-loaded TrxR2 was transfected into N2a cells to up-regulate TrxR2 expression. Then, cell viability was determined via MTT assay and TUNEL assay. Apoptosis was measured via western blotting and ELISA. Oxidative stress was detected via ELISA and flow cytometry. A pathway inhibitor was used to verify the role of the Akt–Parkin pathway in the LPS-mediated N2a cell death in the presence of TrxR2 overexpression. With the help of immunofluorescence assay and western blotting, we found that TrxR2 expression was significantly reduced in response to LPS treatment, and this effect was associated with N2a cell death via apoptosis. At the molecular level, TrxR2 overexpression elevated the activity of the Akt–Parkin pathway, as evidenced by the increased expression of p-Akt and Parkin. Interestingly, inhibition of the Akt–Parkin pathway abolished the regulatory effect of TrxR2 on LPS-treated N2a cells, as evidenced by the decreased cell viability and increased apoptotic ratio. Besides, TrxR2 overexpression also reduced oxidative stress, inflammation factor transcription and mitochondrial apoptosis. However, inhibition of Akt–Parkin axis abrogated the protective effects of TrxR2 on redox balance, mitochondrial performance and cell survival. LPS-mediated neuronal death was linked to a drop in TrxR2 overexpression and the inactivation of the Akt–Parkin pathway. Overexpression of TrxR2 sustained mitochondrial function, inhibited oxidative stress, repressed inflammation response, and blocked mitochondrial apoptosis, finally sending a pro-survival signal for the N2a cells in the setting of LPS-mediated inflammation environment.

Effect of alpha-ketoglutarate and N-acetyl cysteine on cyanide-induced oxidative stress mediated cell death in PC12 cells

2010 ◽  
Vol 26 (5) ◽  
pp. 297-308 ◽  
Author(s):  
RM Satpute ◽  
J. Hariharakrishnan ◽  
R. Bhattacharya
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Pc12 Cells ◽  
Caspase 3 ◽  
Critical Role ◽  
Total Antioxidant Status ◽  
Protective Effects ◽  
Simultaneous Treatment ◽  
Acetyl Cysteine

Cyanide is a mitochondrial poison, which is ubiquitously present in the environment. Cyanide-induced oxidative stress is known to play a key role in mediating the neurotoxicity and cell death in rat pheochromocytoma (PC12) cells. PC12 cells are widely used as a model for neurotoxicity assays in vitro. In the present study, we investigated the protective effects of alpha-ketoglutarate (A-KG), a potential cyanide antidote, and N-acetyl cysteine (NAC), an antioxidant against toxicity of cyanide in PC12 cells. Cells were treated with various concentrations (0.625—1.25 mM) of potassium cyanide (KCN) for 4 hours, in the presence or absence of simultaneous treatment of A-KG (0.5 mM) and NAC (0.25 mM). Cyanide caused marked decrease in the levels of cellular antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). Lipid peroxidation indicated by elevated levels of malondialdehyde (MDA) was found to be accompanied by decreased levels of reduced glutathione (GSH) and total antioxidant status (TAS) of the cells. Cyanide-treated cells showed notable increase in caspase-3 activity and induction of apoptotic type of cell death after 24 hours. A-KG and NAC alone were very effective in restoring the levels of GSH and TAS, but together they significantly resolved the effects of cyanide on antioxidant enzymes, MDA levels, and caspase-3 activity. The present study reveals that combination of A-KG and NAC has critical role in abbrogating the oxidative stress-mediated toxicity of cyanide in PC12 cells. The results suggest potential role of A-KG and NAC in cyanide antagonism.

scholarly journals Hesperetin protects SH-SY5Y cells against 6- hydroxydopamine-induced neurotoxicity via activation of NRF2/ARE signaling pathways

2020 ◽  
Vol 19 (6) ◽  
pp. 1197-1201 ◽  
Author(s):  
Jing Li ◽  
Yue Liu ◽  
Li Wang ◽  
Zhaowei Gu ◽  
Zhigang Huan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Viability ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Ldh Release ◽  
6 Hydroxydopamine

Purpose: To investigation the protective effects of hesperetin against 6-hydroxydopamine (6-OHDA)- induced neurotoxicity. Methods: SH-SY5Y cells were incubated with 6-OHDA to create an in vitro model of neurotoxicity. This model was used to test the neuroprotective effects of hesperetin. Cell viability was assessed by MTT and lactate dehydrogenase (LDH) release assays. Flow cytometry and western blot were used to quantify apoptosis. Oxidative stress was evaluated by determining intracellular glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS). Results: In SH-SY5Y cells, treatment with 6-OHDA decreased cell viability and promoted LDH release. However, exogenous hesperetin protected against 6-OHDA-mediated toxicity. Similarly, although incubation with 6-OHDA induced apoptosis and increased cleaved caspase-3 and -9 levels, treatment with hesperetin protected against these effects. Treatment with 6-OHDA also led to significant oxidative stress, as indicated by reduced GSH and SOD levels and increased MDA and ROS levels in SH-SY5Y cells. However, these changes were reversed by pre-treatment with hesperetin. Of interest, hesperetin led to changes in 6-OHDA-induced expression of NRF2, heme oxygenase-1 (HO-1), glutamate-cysteine ligase (GCL) catalytic subunit (GCLC), and GCL modulatory (GCLM). Conclusion: Hesperetin protects against cell toxicity, apoptosis, and oxidative stress via activation of NRF2 pathway in a 6-OHDA-induced model of neurotoxicity. Future studies should investigate the use of hesperetin as a potential therapeutic approach for prevention or management of Parkinson’s disease. Keywords: Hesperetin, 6-OHDA, Neurotoxicity, NRF2, Parkinson’s disease

Tanshinone IIA Suppresses Hypoxia-induced Apoptosis in Medial Vestibular Nucleus Cells Via a Skp2/BKCa Axis

2020 ◽  
Vol 26 (33) ◽  
pp. 4185-4194
Author(s):  
Jing-Jing Zhu ◽  
Shu-Hui Wu ◽  
Xiang Chen ◽  
Ting-Ting Jiang ◽  
Xin-Qian Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Cell Damage ◽  
Vestibular Nucleus ◽  
Tanshinone Iia ◽  
Medial Vestibular Nucleus ◽  
Protective Effects ◽  
Induced Apoptosis

Background: The aim of the present study was to investigate the protective effects of Tanshinone IIA (Tan IIA) on hypoxia-induced injury in the medial vestibular nucleus (MVN) cells. Methods: An in vitro hypoxia model was established using MVN cells exposed to hypoxia. The hypoxia-induced cell damage was confirmed by assessing cell viability, apoptosis and expression of apoptosis-associated proteins. Oxidative stress and related indicators were also measured following hypoxia modeling and Tan IIA treatment, and the genes potentially involved in the response were predicted using multiple GEO datasets. Results: The results of the present study showed that Tan IIA significantly increased cell viability, decreased cell apoptosis and decreased the ratio of Bax/Bcl-2 in hypoxia treated cells. In addition, hypoxia treatment increased oxidative stress in MVN cells, and treatment with Tan IIA reduced the oxidative stress. The expression of SPhase Kinase Associated Protein 2 (SKP2) was upregulated in hypoxia treated cells, and Tan IIA treatment reduced the expression of SKP2. Mechanistically, SKP2 interacted with large-conductance Ca2+-activated K+ channels (BKCa), regulating its expression, and BKCa knockdown alleviated the protective effects of Tan IIA on hypoxia induced cell apoptosis. Conclusion: The results of the present study suggested that Tan IIA had a protective effect on hypoxia-induced cell damage through its anti-apoptotic and anti-oxidative activity via an SKP2/BKCa axis. These findings suggest that Tan IIA may be a potential therapeutic for the treatment of hypoxia-induced vertigo.

scholarly journals Protective Effect of Natural Antioxidant Compounds on Methimazole Induced Oxidative Stress in a Feline Kidney Epithelial Cell Line (CRFK)

2021 ◽  
Vol 8 (10) ◽  
pp. 220
Author(s):  
Flavia Girolami ◽  
Alessia Candellone ◽  
Watanya Jarriyawattanachaikul ◽  
Giorgia Meineri ◽  
Carlo Nebbia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Antithyroid Drug ◽  
Epithelial Cell Line ◽  
Antioxidant Compounds ◽  
Maximum Plasma ◽  
Dependent Manner ◽  
Protective Effects ◽  
Renal Epithelium

The treatment of choice for feline hyperthyroidism is the administration of the antithyroid drug methimazole. Both the endocrinopathy and the drug adverse reactions (e.g., hepatotoxicosis, gastrointestinal disorders, and renal injury) are partly due to oxidative stress and redox unbalance. This study investigated the free radical production and the impairment of the antioxidant barrier induced by methimazole in an in vitro model of feline renal epithelium. The protective effects of quercetin and resveratrol were also explored. CRFK cells were incubated with a methimazole concentration equivalent to the maximum plasma levels in orally treated cats (4 µM), in the presence or absence of either one of the two selected antioxidants at different time-points (up to 72 h). Cell viability, ROS production, GSH levels, and mRNA expression of antioxidant enzymes (i.e., CAT, SOD, GPx, and GST) were assessed. Methimazole impaired cell viability and increased ROS levels in a time-dependent manner. Similarly, GSH content and CAT, SOD, and GPx3 expression were higher compared with control cells. Such effects were significantly counteracted by quercetin. These results provide new insights about the mechanisms underlying the methimazole-related side effects frequently observed in hyperthyroid cats. They also support the use of quercetin in the management of feline hyperthyroidism.

Antidepressant Effects of Vaccinium bracteatum via Protection Against Hydrogen Peroxide-Induced Oxidative Stress and Apoptosis

2018 ◽  
Vol 46 (07) ◽  
pp. 1499-1518 ◽  
Author(s):  
Dool-Ri Oh ◽  
Yujin Kim ◽  
Eun-Jin Choi ◽  
Ara Jo ◽  
Jawon Shin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Cell Death ◽  
Neuronal Damage ◽  
In Vitro Models ◽  
Monoamine Oxidase A ◽  
Protective Effects ◽  
Mao A ◽  
Anti Oxidant

The present study evaluates the anti-oxidative stress activity of Vaccinium bracteatum Thunb. fruit extract (VBFW) to identify the mechanisms responsible for its antidepressant-like effects. To evaluate the antidepressant and anti-oxidant effects of VBFW, malondialdehyde (MDA), serotonin transporter (SERT), and monoamine oxidase A (MAO-A) levels were measured in a mouse model of chronic restraint stress (CRS). The underlying mechanisms preventing oxidative stress and neuronal apoptosis were investigated using in vitro models of hydrogen peroxide (H2O[Formula: see text]-induced neuronal damage. The results showed that VBFW treatment (200[Formula: see text]mg/kg) significantly reduced MDA, SERT, and MAO-A levels in the prefrontal cortex of CRS mice. Furthermore, VBFW (30[Formula: see text][Formula: see text]g/mL) exhibited protective effects against H2O2-induced cell death via inhibition of the H2O2-induced increase in Bax and decrease in Bcl-2 levels within the mitochondria of SH-SY5Y cells. Furthermore, VBFW (10 and 30[Formula: see text][Formula: see text]g/mL) exerted protective effects against H2O2-induced cell death through inhibition of key mitochondria-associated apoptotic proteins such as cytochrome c, caspase-3 and PARP. Additionally, VBFW (10 and 30[Formula: see text][Formula: see text]g/mL) could improve the activity of anti-oxidant enzymes (such as SOD and catalase) in H2O2-treated SH-SY5Y cells. These results suggest that the antidepressant and anti-oxidant effects of VBFW might be mediated by the regulation of SERT and MAO-A, and possibly associated with regulation of oxidative stress-induced apoptosis.

scholarly journals Protection Against Oxidative Stress-Induced Retinal Cell Death by Compounds Isolated From Ehretia asperula

2021 ◽  
Vol 16 (12) ◽  
pp. 1934578X2110679
Author(s):  
Tam Thi Le ◽  
Tae Kyeom Kang ◽  
Ha Thi Do ◽  
Trong Duc Nghiem ◽  
Wook-Bin Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cell Viability ◽  
Rosmarinic Acid ◽  
Retinal Cell ◽  
Published Data ◽  
Protective Effects ◽  
Chemical Structures ◽  
Wide Range ◽  
Ethanolic Extracts

Ehretia asperula ( E asperula) is a well-known traditional medicinal plant in Vietnam with potent activity against a wide range of diseases, including hepatitis B and various cancers. Although E asperula has been used in traditional medicine, the efficacy of E asperula and its bioactive components on retinal degenerative diseases has not been fully evaluated. In present this study, we found that ethanolic extracts of E asperula increased cell viability in retinal precursor cells exposed to glutamate/BSO-induced excitotoxicity/oxidative stress. The major responsible bioactive compounds were rosmarinic acid and methylrosmarinic acid. First, 10 known compounds were isolated from E asperula leaves. Their chemical structures were determined using 1D and 2D nuclear magnetic resonance, and compared with published data. Using high-performance liquid chromatography, we determined the content of 4 compounds in E asperula extract: rosmarinic acid, lithospermic acid B, astragalin, and kaempferol 3-rutinoside. The most abundant of these compounds was lithospermic acid B. The protective effects of the pure compounds and ethanolic extracts against excitotoxicity and oxidative stress-induced retinal cell death were tested in R28 cells. Both 70% and 95% ethanolic extracts of E asperula increased cell viability in these conditions. Rosmarinic acid and methyl rosmarinic acid were more effective at protecting against retinal cell death and elevated reactive oxygen species in cells subjected to glutamate/BSO-induced excitotoxicity/oxidative stress. These findings suggested that E asperula could potentially be used to treat retinal degeneration.

scholarly journals Protective effects of isothiocyanates on blood-CSF barrier disruption induced by oxidative stress

2012 ◽  
Vol 303 (1) ◽  
pp. R1-R7 ◽  
Author(s):  
Jianming Xiang ◽  
Gina N. Alesi ◽  
Ningna Zhou ◽  
Richard F Keep
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neurological Disorders ◽  
Nuclear Translocation ◽  
Normal Function ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Protective Effects ◽  
Brain Response

The choroid plexuses (CPs) form the blood-cerebrospinal fluid (CSF) barrier (BCSFB) and play an important role in maintaining brain normal function and the brain response to injury. Many neurological disorders are associated with oxidative stress that can impact CP function. This study examined the effects of isothiocyanates, an abundant component in cruciferous vegetables, on H2O2-induced BCSFB disruption and CP cell death in vitro. It further examined the potential role of a transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), in isothiocyanate-induced protection. Sulforaphane (SF) significantly reduced H2O2-induced BCSFB disruption as assessed by transepithelial electrical resistance (29 ± 7% reduction vs. 92 ± 2% decrease in controls) and [3H]mannitol permeability. Allyl-isothiocyanate (AITC) had a similar protective effect. H2O2-induced epithelial cell death was also reduced by these isothiocyanates. In primary CP cells, SF and AITC reduced cell death by 42 ± 3% and 53 ± 10%, respectively. Similar protection was found in a CP cell line Z310. Protection was only found with pretreatment for 12–48 h and not with acute exposure (1 h). The protective effects of SF and AITC were associated with Nrf2 nuclear translocation and upregulated expression of antioxidative systems regulated by Nrf2, including heme oxygenase-1, NAD(P)H quinine oxidoreductase, and cysteine/glutamate exchange transporter. Thus isothiocyanates, as diet or medicine, may be a method for protecting BCSFB in neurological disorders.

scholarly journals Thunbergia laurifolia Leaf Extract Inhibits Glutamate-Induced Neurotoxicity and Cell Death through Mitophagy Signaling

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1678
Author(s):  
Wudtipong Vongthip ◽  
Chanin Sillapachaiyaporn ◽  
Kyu-Won Kim ◽  
Monruedee Sukprasansap ◽  
Tewin Tencomnao
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Antioxidant Enzymes ◽  
Neuronal Death ◽  
Leaf Extract ◽  
Mitochondrial Protein ◽  
Dependent Manner ◽  
Protective Effects ◽  
Concentration Dependent Manner ◽  
Thunbergia Laurifolia

Oxidative stress plays a crucial role in neurodegeneration. Therefore, reducing oxidative stress in the brain is an important strategy to prevent neurodegenerative disorders. Thunbergia laurifolia (Rang-jued) is well known as an herbal tea in Thailand. Here, we aimed to determine the protective effects of T. laurifolia leaf extract (TLE) on glutamate-induced oxidative stress toxicity and mitophagy-mediated cell death in mouse hippocampal cells (HT-22). Our results reveal that TLE possesses a high level of bioactive antioxidants by LC–MS technique. We found that the pre-treatment of cells with TLE prevented glutamate-induced neuronal death in a concentration-dependent manner. TLE reduced the intracellular ROS and maintained the mitochondrial membrane potential caused by glutamate. Moreover, TLE upregulated the gene expression of antioxidant enzymes (SOD1, SOD2, CAT, and GPx). Interestingly, glutamate also induced the activation of the mitophagy process. However, TLE could reverse this activity by inhibiting autophagic protein (LC3B-II/LC3B-I) activation and increasing a specific mitochondrial protein (TOM20). Our results suggest that excessive glutamate can cause neuronal death through mitophagy-mediated cell death signaling in HT-22 cells. Our findings indicate that TLE protects cells from neuronal death by stimulating the endogenous antioxidant enzymes and inhibiting glutamate-induced oxidative toxicity via the mitophagy–autophagy pathway. TLE might have potential as an alternative or therapeutic approach in neurodegenerative diseases.

scholarly journals Resveratrol Alleviates Vascular Endothelial Damage Caused by Lower-Extremity Ischemia Reperfusion (I/R) through Regulating Keap1/Nrf2 Signaling-Mediated Oxidative Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Xiaojun Song ◽  
Zhili Liu ◽  
Rong Zeng ◽  
Jiang Shao ◽  
Yuehong Zheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lower Extremity ◽  
Cell Viability ◽  
Ischemia Reperfusion ◽  
Endothelial Damage ◽  
Pathological State ◽  
Vascular Endothelial ◽  
Protective Effects ◽  
Commercial Kits

The present study aims to investigate the protective effects of Resveratrol (RSV) against vascular endothelial damage caused by lower-extremity I/R and the underlying preliminary mechanism. The in vitro hypoxia reoxygenation (HR) model was established on HUVECs. Lower-extremity I/R model was established on rats followed by being treated with RSV and the pathological state of artery was evaluated by HE and EVG staining, while the apoptotic state of artery was detected by TUNEL assay. The cell viability was detected by MTT assay and the apoptotic state of cells was determined by Hoechst test and flow cytometry assay. DCFH-DA staining was used to measure the level of ROS and the production of MDA and SOD was measured by commercial kits. The expression level of Nrf2, Keap1, HO-1, Bcl-2, Bax, and Caspase-3 in cells was determined by Western blot. Nrf2 was knocked down by siRNA technology. Overall, our data indicated that increased cell viability, declined apoptotic rate, and alleviated oxidative stress were observed in RSV treated HR HUVECs, which were significantly reversed by knocking down Nrf2. Animal experiment revealed that the pathological and apoptotic state of femoral artery were dramatically ameliorated by the treatment of RSV, accompanied by the alleviated oxidative stress, which were abolished by the co-administration of ML385, an inhibitor of Nrf2. Taken together, our data revealed that RSV might alleviate vascular endothelial injury induced by lower-extremity I/R injury through regulating Keap1/Nrf2 signaling-mediated oxidative stress.

scholarly journals Probucol enhances the therapeutic efficiency of mesenchymal stem cells in the treatment of erectile dysfunction in diabetic rats by prolonging their survival time via Nrf2 pathway

2020 ◽  
Author(s):  
Haoran Wang ◽  
Keqin Zhang ◽  
Zheng Ruan ◽  
Dingqi Sun ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Cell Viability ◽  
Survival Time ◽  
Western Blotting ◽  
Dependent Manner ◽  
Nrf2 Pathway ◽  
Therapeutic Efficiency ◽  
Dose Dependent

Abstract Background: Intracavernous injection of mesenchymal stem cells (MSCs) is a promising method for Diabetic mellitus-induced erectile dysfunction (DMED), but short survival time of MSCs in cavernous is fatal defect for therapy. This study investigated therapeutic efficiency and potential mechanism of probucol combined with MSCs. Methods: In vivo study, total forty-eight 10-week-old male Sprague-Dawley (SD) rats were used in this study. Twelve rats received intraperitoneal injection of PBS as Sham Group; the rest received intraperitoneal injection of 60mg/kg streptozotocin to establish DM models. DM rats were randomly divided into three groups: received intracavernosal (IC) injection of either PBS (DM Group), MSCs (M Group), and administrated probucol after intracavernosal injection of MSCs (P+M Group). Erectile function was assessed by electrical stimulation of the cavernous nerves with real-time intracavernous pressure measurement. After euthanasia, penile tissue was investigated for histologic examination and Western blotting. In vitro experiment, H2O2 was used to create oxidative stress environment to detect changes in cell viability. CCK8 was used to measure cell viability of MSCs treated with or without probucol. Intracellular ROS changes were detected by flow cytometry. Autophagy and apoptosis were detected by Western blotting and confocal microscopy.Results: Recovery of erectile function was observed in the P+M Group. The combination therapy decreased fibrosis and increased endothelial function compared with MSCs therapy alone. Western blotting results confirmed the increased expression of Nrf2 and HO-1 in cavernous body. H2O2 induced high oxidative stress and reduced cell viability in vitro, which was gradually reversed with increased concentration of probucol. H2O2 reduced Nrf2 expression, which was reversed by probucol's intervention. Furthermore, the expression of Bax, Caspase3 and Cleaved-Caspase3 decreased, and the expression of Bcl-2 increased in a dose-dependent manner because of probucol's intervention. In addition, Beclin1 and LC3II both increased in a dose-dependent manner. Meanwhile, the expression of P62 decreased. In study of autophagy flux, we found probucol didn’t block it. Conclusion: Probucol enhanced therapeutic efficiency of MSCs in DMED by prolonging their survival time, which mediated through improving the transplanted microenvironment of MSCs, increasing self-antioxidant ability of MSCs, strengthening protective autophagy and inhibiting apoptosis of MSCs via Nrf2 pathway.

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