GABAB Receptor-Mediated PI3K/Akt Signaling Pathway Alleviates Oxidative Stress and Neuronal Cell Injury in a Rat Model of Alzheimer’s Disease

2020 ◽  
pp. 1-14
Author(s):  
Zhiqing Sun ◽  
Lei Sun ◽  
Lixiang Tu
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Signaling Pathway ◽  
Rat Model ◽  
Cell Injury ◽  
Gabab Receptor ◽  
Neuronal Cell ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Model Of Alzheimer’S Disease

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 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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