Tea Polyphenols Attenuate Methamphetamine-Induced Neuronal Damage in PC12 Cells by Alleviating Oxidative Stress and Promoting DNA Repair

Background and Objectives: Beta-amyloid (Aβ) has pivotal functions in the pathogenesis of Alzheimer’s Disease (AD). The main purpose of this study is to explore the protective role and possible mechanisms of matrine against Aβ25–35-induced neurotoxicity in PC12 cells. Materials and Methods: A vitro model that involved Aβ25–35-induced neuronal damage in PC12 cells was adopted in the present study. Cell viability and apoptosis of PC12 cells were determined by CCK-8 assay and TUNEL staining, respectively. Intracellular ROS levels were determined by DCFH-DA probe and levels of TNFα, IL-6 and IL-1β were assessed by ELISA assay. In addition, telomerase reverse transcriptase (TERT) levels were determined by ELISA assay and telomere lengths were examined by real-time quantitative PCR analysis to assess telomerase activities. Furthermore, vital proteins related to cell apoptosis and hallmarks of senescence were detected by western blot analysis. Results: Matrine (10, 20, 50 μg/ml) dose-dependently protected cell viability against Aβ25–35 cytotoxicity in PC12 cells. Meanwhile, matrine at 10, 20, 50 μg/ml markedly reduced ROS production and downregulated the levels of TNFα, IL-6 and IL-1β in Aβ25–35-injuried PC12 cells. The results also proved that matrine may restore telomerase activities and telomere lengths in Aβ25–35-injuried PC12 cells by inhibiting inflammatory responses and oxidative stress. Neuronal apoptosis induced by Aβ25–35 were reversed upon cotreatment with matrine. Moreover, matrine markedly mitigated Aβ25–35 induced cell senescence in a concentration-dependentmanner. Conclusion: Our findings demonstrated that matrine protected PC12 cells against Aβ25–35-induced cytotoxicity, oxidative stress, inflammation, neuronal apoptosis and cell senescence.

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In VitroEffects of Tea Polyphenols on Redox Metabolism, Oxidative Stress, and Apoptosis in PC12 Cells

Annals of the New York Academy of Sciences ◽

10.1196/annals.1414.037 ◽

2008 ◽

Vol 1138 (1) ◽

pp. 358-365 ◽

Cited By ~ 21

Author(s):

Haider Raza ◽

Annie John

Keyword(s):

Oxidative Stress ◽

Pc12 Cells ◽

Tea Polyphenols ◽

Redox Metabolism

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Protective Effects and Mechanism of Hyperoside in PC12 Cells Against Oxidative Stress Injury Induced by Hydrogen Peroxide

Natural Product Communications ◽

10.1177/1934578x211015126 ◽

2021 ◽

Vol 16 (5) ◽

pp. 1934578X2110151

Author(s):

Yan Feng ◽

Dongxu Wang ◽

Qi Wang ◽

Zhifeng Li ◽

Shi-Lin Yang ◽

...

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Neurodegenerative Diseases ◽

Pc12 Cells ◽

Neuronal Damage ◽

Neuroprotective Effect ◽

Natural Antioxidants ◽

Protective Effects ◽

Stress Injury ◽

Stress Damage

As the aging phenomenon continues to increase, the incidence of neurodegenerative diseases continues to increase annually. As one of the significant contributive factors of neurodegenerative diseases, oxidative stress damage has received extensive attention in recent years. Oxidative stress plays an important role in neuronal damage through various apoptotic mechanisms related to neurodegenerative diseases. The use of natural antioxidants to combat oxidative stress may be a useful approach in delaying disease progression. In this study, we explored the neuroprotective effect of hyperoside on rat pheochromoma (PC12) cells. Specifically, the antioxidant effect and mechanism of hyperoside in hydrogen peroxide (H2O2)-induced cellular cytotoxicity were investigated. Our results showed that hyperoside could significantly increase the survival rate of rat PC12 cells when exposed to H2O2. In addition, hyperoside regulated the expression of genes and proteins in the corresponding pathways by up-regulating the phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), and light chain 3β (LC3B) pathways and down-regulating the nuclear factor-ᴋ-gene binding (NF-κB), Bcl2-associated X (Bax), cysteinyl aspartate specific proteinase 3 (Caspase 3), and P62 pathways, thereby inhibiting cell apoptosis. Therefore, hyperoside can effectively inhibit H2O2-induced oxidative stress damage by regulating inflammation, autophagy, and apoptosis-related pathways.

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DNA repair protein DNA-PK protects PC12 cells from oxidative stress-induced apoptosis involving AKT phosphorylation

Molecular Biology Reports ◽

10.1007/s11033-021-06934-5 ◽

2021 ◽

Author(s):

Alessio Cardinale ◽

Serena Saladini ◽

Leonardo Lupacchini ◽

Irene Ruspantini ◽

Chiara De Dominicis ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Dna Repair ◽

Pc12 Cells ◽

Cellular Response ◽

Tumor Cell Line ◽

Dsb Repair ◽

Akt Phosphorylation ◽

Induced Apoptosis

Abstract Background Emerging evidence suggest that DNA-PK complex plays a role in the cellular response to oxidative stress, in addition to its function of double strand break (DSB) repair. In this study we evaluated whether DNA-PK participates in oxidative stress response and whether this role is independent of its function in DNA repair. Methods and results We used a model of H2O2-induced DNA damage in PC12 cells (rat pheochromocytoma), a well-known neuronal tumor cell line. We found that H2O2 treatment of PC12 cells induces an increase in DNA-PK protein complex levels, along with an elevation of DNA damage, measured both by the formation of γΗ2ΑX foci, detected by immunofluorescence, and γH2AX levels detected by western blot analysis. After 24 h of cell recovery, γΗ2ΑX foci are repaired both in the absence and presence of DNA-PK kinase inhibitor NU7026, while an increase of apoptotic cells is observed when DNA-PK activity is inhibited, as revealed by counting pycnotic nuclei and confirmed by FACS analysis. Our results suggest a role of DNA-PK as an anti-apoptotic factor in proliferating PC12 cells under oxidative stress conditions. The anti-apoptotic role of DNA-PK is associated with AKT phosphorylation in Ser473. On the contrary, in differentiated PC12 cells, were the main pathway to repair DSBs is DNA-PK-mediated, the inhibition of DNA-PK activity causes an accumulation of DNA damage. Conclusions Taken together, our results show that DNA-PK can protect cells from oxidative stress induced-apoptosis independently from its function of DSB repair enzyme. Graphical Abstract

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Neuroprotective Effects of Extracts from the Radix Curcuma aromatica on H2O2-induced Damage in PC12 Cells

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207321666181005121457 ◽

2018 ◽

Vol 21 (8) ◽

pp. 571-582 ◽

Cited By ~ 1

Author(s):

Juxiang Liu ◽

Lianli Zhang ◽

Dan Liu ◽

Baocai Li ◽

Mi Zhang

Keyword(s):

Oxidative Stress ◽

Pc12 Cells ◽

Caspase 3 ◽

Cell Damage ◽

Positive Control ◽

Neuroprotective Activity ◽

Antioxidant Enzyme Activities ◽

Morphologic Change ◽

Neuroprotective Effects ◽

Etoh Extract

Aim & Objectives: Curcuminoids are characteristic constituents in Curcuma, displaying obviously neuroprotective activities against oxidative stress. As one of the Traditional Chinese Medicines from Curcuma, the radix of Curcuma aromatica is also rich in those chemicals, but its neuroprotective activity and mechanism remain unknown. The aim of the current study is to evaluate the neuroprotective effects of extracts from the radix of C. aromatica (ECAs) on H2O2-damaged PC12 cells. Material and Methods: The model of oxidative stress damage was established by treatment of 400 µM H2O2 on PC12 to induce cell damage. After the treatment of ECWs for 24 h, the cell viability, LDH, SOD, CAT and GSH were measured to evaluate the neuroprotection of ECAs on that model. The potential action mechanism was studied by measurement of level of ROS, cell apoptosis rate, mitochondrial membrane potential (MMP), morphologic change, the intracellular Ca2+ content (F340/F380) and the expressions of Bcl-2, Bax and Caspase-3. Additionally, the constituents from tested extracts were analyzed by HPLC-DAD-Q-TOF-MS method. Results: Compared with a positive control, Vitamin E, 10 µg/ml of 95% EtOH extract (HCECA) and 75% EtOH extract (MCECA) can markedly increase the rate of cell survival and enhance the antioxidant enzyme activities of SOD, CAT, increase the levels of GSH, decrease LDH release and the level of ROS, attenuate the intracellular Ca2+ overloading, reduce the cell apoptotic rate and stabilize MMP, down-regulate Bcl-2 expression, up-regulate Bax and caspase-3 expression, and improve the change of cell morphology. The chemical analysis showed that diarylheptanoids and sesquiterpenoids are the major chemicals in tested extracts and the former were richer in HCECA and MCECA than others. Conclusions: These findings indicated that the effects of HCECA and MCECA on inhibiting the cells damage induced by H2O2 in PC12 are better than other extracts from the radix of C. aromatica, and the active constituents with neuroprotective effects consisting in those two active extracts are diarylheptanoids.

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Effect of Fluoxetine on Brain Oxidative Stress, Neuronal Damage and Behavioural Induced in the Olfactory Bulbectomy Model of Depression

Letters in Drug Design & Discovery ◽

10.2174/157018007784620013 ◽

2007 ◽

Vol 4 (4) ◽

pp. 305-310 ◽

Cited By ~ 6

Author(s):

Isaac Tunez ◽

Francisco Medina ◽

Ignacio Jimena ◽

María del Munoz

Keyword(s):

Oxidative Stress ◽

Neuronal Damage ◽

Olfactory Bulbectomy ◽

Brain Oxidative Stress

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Genetic variants and cognitive functions in patients with brain tumors

Neuro-Oncology ◽

10.1093/neuonc/noz094 ◽

2019 ◽

Vol 21 (10) ◽

pp. 1297-1309 ◽

Cited By ~ 5

Author(s):

Denise D Correa ◽

Jaya Satagopan ◽

Axel Martin ◽

Erica Braun ◽

Maria Kryza-Lacombe ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Cycle ◽

Dna Repair ◽

Brain Tumor ◽

Brain Tumors ◽

Cell Cycle Regulation ◽

Cognitive Outcome ◽

Cholesterol Transport ◽

Tumor Patients ◽

Cycle Regulation

AbstractBackgroundPatients with brain tumors treated with radiotherapy (RT) and chemotherapy (CT) often experience cognitive dysfunction. We reported that single nucleotide polymorphisms (SNPs) in the APOE, COMT, and BDNF genes may influence cognition in brain tumor patients. In this study, we assessed whether genes associated with late-onset Alzheimer’s disease (LOAD), inflammation, cholesterol transport, dopamine and myelin regulation, and DNA repair may influence cognitive outcome in this population.MethodsOne hundred and fifty brain tumor patients treated with RT ± CT or CT alone completed a neurocognitive assessment and provided a blood sample for genotyping. We genotyped genes/SNPs in these pathways: (i) LOAD risk/inflammation/cholesterol transport, (ii) dopamine regulation, (iii) myelin regulation, (iv) DNA repair, (v) blood–brain barrier disruption, (vi) cell cycle regulation, and (vii) response to oxidative stress. White matter (WM) abnormalities were rated on brain MRIs.ResultsMultivariable linear regression analysis with Bayesian shrinkage estimation of SNP effects, adjusting for relevant demographic, disease, and treatment variables, indicated strong associations (posterior association summary [PAS] ≥ 0.95) among tests of attention, executive functions, and memory and 33 SNPs in genes involved in: LOAD/inflammation/cholesterol transport (eg, PDE7A, IL-6), dopamine regulation (eg, DRD1, COMT), myelin repair (eg, TCF4), DNA repair (eg, RAD51), cell cycle regulation (eg, SESN1), and response to oxidative stress (eg, GSTP1). The SNPs were not significantly associated with WM abnormalities.ConclusionThis novel study suggests that polymorphisms in genes involved in aging and inflammation, dopamine, myelin and cell cycle regulation, and DNA repair and response to oxidative stress may be associated with cognitive outcome in patients with brain tumors.

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