scholarly journals Effects of Carbazole Derivatives on Neurite Outgrowth and Hydrogen Peroxide-Induced Cytotoxicity in Neuro2a Cells

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1366 ◽  
Author(s):  
Yoshiko Furukawa ◽  
Atsushi Sawamoto ◽  
Mizuki Yamaoka ◽  
Makiko Nakaya ◽  
Yuhzo Hieda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Cell Death ◽  
Neurite Outgrowth ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Anti Oxidant ◽  
Neuro2a Cells ◽  
Cerebral Ischemic

Many studies have demonstrated that oxidative stress plays an important role in several ailments including neurodegenerative diseases and cerebral ischemic injury. Previously we synthesized some carbazole compounds that have anti-oxidant ability in vitro. In this present study, we found that one of these 22 carbazole compounds, compound 13 (3-ethoxy-1-hydroxy-8- methoxy-2-methylcarbazole-5-carbaldehyde), had the ability to protect neuro2a cells from hydrogen peroxide-induced cell death. It is well known that neurite loss is one of the cardinal features of neuronal injury. Our present study revealed that compound 13 had the ability to induce neurite outgrowth through the PI3K/Akt signaling pathway in neuro2a cells. These findings suggest that compound 13 might exert a neurotrophic effect and thus be a useful therapy for the treatment of brain injury.

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 Chrysanthemum indicum Prevents Hydrogen Peroxide-Induced Neurotoxicity by Activating the TrkB/Akt Signaling Pathway in Hippocampal Neuronal Cells

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3690
Author(s):  
Yun Hee Jeong ◽  
Tae In Kim ◽  
You-Chang Oh ◽  
Jin Yeul Ma
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Oxidative Damage ◽  
Neurodegenerative Diseases ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Ht22 Cells ◽  
Chrysanthemum Indicum ◽  
Antioxidant Effects

Oxidative stress-mediated neuronal damage is associated with the pathogenesis and development of neurodegenerative diseases. Chrysanthemum indicum has antioxidant properties. However, the neuroprotective effects and the cellular mechanism of C. indicum ethanol extract (CIE) against oxidative damage in hippocampal neuronal cells have not been clearly elucidated. Therefore, this study investigated whether CIE has protective effects against hydrogen peroxide (H2O2)-induced oxidative toxicity in HT22 cells. CIE pretreatment significantly improved neuronal cell viability. Moreover, the formation of intracellular reactive oxygen species and apoptotic bodies, and mitochondrial depolarization were significantly reduced in HT22 cells with H2O2-induced oxidative toxicity. Furthermore, CIE increased the phosphorylation of tropomyosin-related kinase receptor B (TrkB), protein kinase B (Akt), cAMP response element-binding protein, the expression of brain-derived neurotrophic factor, antioxidant enzymes, and the nuclear translocation of nuclear factor erythroid 2-related factor 2 by activating the TrkB/Akt signaling pathway. In contrast, the addition of K252a, a TrkB inhibitor, or MK-2206, an Akt-selective inhibitor, reduced the neuroprotective and antioxidant effects of CIE. Taken together; CIE exhibits neuroprotective and antioxidant effects against oxidative damage. Therefore, it can be a potential agent for treating oxidative stress-related neurodegenerative diseases.

Resveratrol upregulates miR-455-5p to antagonize cisplatin ototoxicity via modulating the PTEN–PI3K–AKT axis

2021 ◽  
pp. 1-11
Author(s):  
Yupeng Liu ◽  
Hui Wu ◽  
Fan Zhang ◽  
Jun Yang ◽  
Jingchun He
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Cell Injury ◽  
Auditory Brainstem ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Brainstem Response ◽  
And Oxidative Stress

Resveratrol is a non-flavonoid polyphenol compound that exists in many plants, and is considered an antitoxin. This study explores the effects from the regulation of miR-455-5p by resveratrol on cisplatin-induced ototoxicity via the PTEN–PI3K–AKT signaling pathway. For this, House Ear Institute–Organ of Corti 1 (HEI-OC1) cells were transfected with miR-455-5p inhibitor and treated with cisplatin and resveratrol, then cell proliferation, apoptosis, and oxidative stress were evaluated. A mouse model of hearing loss was established, and these mice were treated with cisplatin, resveratrol, or cisplatin combined with resveratrol, by intraperitoneal injection. The auditory brainstem response (ABR) threshold was measured, and hair cells were examined using immunofluorescence staining. The expression levels of miR-455-5p, PTEN, and PI3K/Akt proteins were examined. The results from our in-vitro experiments indicate that resveratrol promoted viability and reduced apoptosis and oxidative stress in cisplatin-induced HEI-OC1 cells. Resveratrol upregulated miR-455-5p, downregulated PTEN, and activated the PI3K–Akt axis. These effects of resveratrol were reversed by knock-down of miR-455-5p. The results from our in-vivo experiments indicate that resveratrol protected hearing and inhibited the hair-cell injury caused by cisplatin ototoxicity. Resveratrol also upregulated miR-455-5p, downregulated PTEN, and activated the PTEN–PI3K–Akt axis in cochlear tissues from cisplatin-treated mice. These results indicate that resveratrol upregulates miR-455-5p to target PTEN and activate the PI3K–Akt signaling pathway to counteract cisplatin ototoxicity.

scholarly journals Maresin 1 protects the liver against ischemia/reperfusion injury via the ALXR/Akt signaling pathway

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Da Tang ◽  
Guang Fu ◽  
Wenbo Li ◽  
Ping Sun ◽  
Patricia A. Loughran ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Serum Aminotransferase ◽  
Primary Mouse ◽  
Maresin 1

Abstract Background Hepatic ischemia/reperfusion (I/R) injury can be a major complication following liver surgery contributing to post-operative liver dysfunction. Maresin 1 (MaR1), a pro-resolving lipid mediator, has been shown to suppress I/R injury. However, the mechanisms that account for the protective effects of MaR1 in I/R injury remain unknown. Methods WT (C57BL/6J) mice were subjected to partial hepatic warm ischemia for 60mins followed by reperfusion. Mice were treated with MaR1 (5-20 ng/mouse), Boc2 (Lipoxin A4 receptor antagonist), LY294002 (Akt inhibitor) or corresponding controls just prior to liver I/R or at the beginning of reperfusion. Blood and liver samples were collected at 6 h post-reperfusion. Serum aminotransferase, histopathologic changes, inflammatory cytokines, and oxidative stress were analyzed to evaluate liver injury. Signaling pathways were also investigated in vitro using primary mouse hepatocyte (HC) cultures to identify underlying mechanisms for MaR1 in liver I/R injury. Results MaR1 treatment significantly reduced ALT and AST levels, diminished necrotic areas, suppressed inflammatory responses, attenuated oxidative stress and decreased hepatocyte apoptosis in liver after I/R. Akt signaling was significantly increased in the MaR1-treated liver I/R group compared with controls. The protective effect of MaR1 was abrogated by pretreatment with Boc2, which together with MaR1-induced Akt activation. MaR1-mediated liver protection was reversed by inhibition of Akt. Conclusions MaR1 protects the liver against hepatic I/R injury via an ALXR/Akt signaling pathway. MaR1 may represent a novel therapeutic agent to mitigate the detrimental effects of I/R-induced liver injury.

scholarly journals Nobiletin enhances the development and quality of bovine embryos in vitro during two key periods of embryonic genome activation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karina Cañón-Beltrán ◽  
Yulia N. Cajas ◽  
Serafín Peréz-Cerezales ◽  
Claudia L. V. Leal ◽  
Ekaitz Agirregoitia ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Mitochondrial Activity ◽  
Bovine Embryos ◽  
Akt Signaling Pathway ◽  
Cell Stage ◽  
Development In Vitro

AbstractIn vitro culture can alter the development and quality of bovine embryos. Therefore, we aimed to evaluate whether nobiletin supplementation during EGA improves embryonic development and blastocyst quality and if it affects PI3K/AKT signaling pathway. In vitro zygotes were cultured in SOF + 5% FCS (Control) or supplemented with 5, 10 or 25 µM nobiletin (Nob5, Nob10, Nob25) or with 0.03% dimethyl-sulfoxide (CDMSO) during minor (2 to 8-cell stage; MNEGA) or major (8 to 16-cell stage; MJEGA) EGA phase. Blastocyst yield on Day 8 was higher in Nob5 (42.7 ± 1.0%) and Nob10 (44.4 ± 1.3%) for MNEGA phase and in Nob10 (61.0 ± 0.8%) for MJEGA phase compared to other groups. Mitochondrial activity was higher and lipid content was reduced in blastocysts produced with nobiletin, irrespective of EGA phase. The mRNA abundance of CDK2, H3-3B, H3-3A, GPX1, NFE2L2 and PPARα transcripts was increased in 8-cells, 16-cells and blastocysts from nobiletin groups. Immunofluorescence analysis revealed immunoreactive proteins for p-AKT forms (Thr308 and Ser473) in bovine blastocysts produced with nobiletin. In conclusion, nobiletin supplementation during EGA has a positive effect on preimplantation bovine embryonic development in vitro and corroborates on the quality improvement of the produced blastocysts which could be modulated by the activation of AKT signaling pathway.

scholarly journals Protective Effects of Gintonin on Reactive Oxygen Species-Induced HT22 Cell Damages: Involvement of LPA1 Receptor-BDNF-AKT Signaling Pathway

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4138
Author(s):  
Yeon-Jin Cho ◽  
Sun-Hye Choi ◽  
Ra-Mi Lee ◽  
Han-Sung Cho ◽  
Hyewhon Rhim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Signaling Pathway ◽  
Reactive Oxygen ◽  
Akt Signaling ◽  
Atp Depletion ◽  
Oxygen Species ◽  
Akt Signaling Pathway ◽  
Neuroprotective Effects ◽  
Lpa1 Receptor

Gintonin is a kind of ginseng-derived glycolipoprotein that acts as an exogenous LPA receptor ligand. Gintonin has in vitro and in vivo neuroprotective effects; however, little is known about the cellular mechanisms underlying the neuroprotection. In the present study, we aimed to clarify how gintonin attenuates iodoacetic acid (IAA)-induced oxidative stress. The mouse hippocampal cell line HT22 was used. Gintonin treatment significantly attenuated IAA-induced reactive oxygen species (ROS) overproduction, ATP depletion, and cell death. However, treatment with Ki16425, an LPA1/3 receptor antagonist, suppressed the neuroprotective effects of gintonin. Gintonin elicited [Ca2⁺]i transients in HT22 cells. Gintonin-mediated [Ca2⁺]i transients through the LPA1 receptor-PLC-IP3 signaling pathway were coupled to increase both the expression and release of BDNF. The released BDNF activated the TrkB receptor. Induction of TrkB phosphorylation was further linked to Akt activation. Phosphorylated Akt reduced IAA-induced oxidative stress and increased cell survival. Our results indicate that gintonin attenuated IAA-induced oxidative stress in neuronal cells by activating the LPA1 receptor-BDNF-TrkB-Akt signaling pathway. One of the gintonin-mediated neuroprotective effects may be achieved via anti-oxidative stress in nervous systems.

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