scholarly journals Long-Term Walnut Oligopeptides Prevents Memory Loss in Aged SAMP8 Mice by Decreasing Oxidative Stress and Down-rRgulating the PI3K/Akt Signaling Pathway in Hippocampus

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 92-92 ◽  
Author(s):  
Meihong Xu ◽  
Qian Du ◽  
Yuntao Hao ◽  
Rui Fan ◽  
Yong Li
Keyword(s):  
Signaling Pathway ◽  
Memory Loss ◽  
Optimal Dose ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Memory Ability ◽  
Beneficial Effects ◽  
Funding Sources ◽  
Underlying Mechanisms ◽  
Samp8 Mice

Abstract Objectives Walnut Oligopeptides (WOPs), the effective component of walnut, has been reported to have a neuron protective effect, but the preventive effect on Alzheimer's disease (AD) related memory loss and the underlying mechanisms have not been well determined. Methods The senescence-accelerated mouse (SAM) is a useful model of AD-related memory impairment. In the present study, SAMP8 mice aged 4 months were chronically treated with ginsenoside (3 dose groups were given WOPs in diet for 6 months). The three groups were treated with WOPs 110, 220 and 440 mg/kg · bw per day, respectively. Placebo-treated aged mice and young ones (4 months old) were used as controls. In addition, SAMR1 mice were used as “normal aging” control. Results The beneficial role of WOPs was manifested in the prevention of memory loss in aged SAMP8 mice. The optimal dose of WOPs is 220 or 440 mg/kg per day. WOPs as found to significantly improve the memory ability of AD rats and anti-oxidase level significantly increased in serum. WOPs also reduced the content of Aβ and p-tau and improved the expression of PI3K and p-Akt/Akt in the hippocampus. Conclusions In conclusion, WOPs could improve the memory ability and reduce the content of Aβ and p-tau in SAMP8. The beneficial effects of WOPs were in part mediated by PI3K/Akt signaling pathway activation. Funding Sources This research was funded by the Bioactive Peptide Innovation Platform in Jilin province.

Contribution of Akt and endothelial nitric oxide synthase to diazoxide-induced late preconditioning

2004 ◽  
Vol 287 (3) ◽  
pp. H1125-H1131 ◽  
Author(s):  
Yigang Wang ◽  
Nauman Ahmad ◽  
Mitsuhiro Kudo ◽  
Muhammad Ashraf
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Fold Increase ◽  
Akt Signaling ◽  
Pi3 Kinase ◽  
No Production ◽  
Akt Signaling Pathway ◽  
Antiapoptotic Effect ◽  
Beneficial Effects ◽  
Late Preconditioning

The opening of mitochondrial ATP-sensitive K+ (mitoKATP) channels has a significant role in delayed ischemic preconditioning, and nitric oxide (NO) is a well-known trigger for its activation. However, the source of NO remains unknown. Phosphorylation of endothelial NO synthase (eNOS) increases NO production and reduces apoptosis through the Akt signaling pathway. To elucidate the Akt signaling pathway involved in the opening and antiapoptotic effect of mitoKATP channel during delayed pharmacological preconditioning, the mitoKATP channel opener diazoxide (DE, 7 μg/kg ip) alone or DE plus Nω-nitro-l-arginine methyl ester (l-NAME, 30 μg/kg iv), an inhibitor of NOS, or wortmannin (WTN, 15 μg/kg iv), an inhibitor of phosphatidylinositol 3′-kinase (PI3 kinase), was administered to wild-type (WT) or eNOS−/− mice during DE treatment. Twenty-four hours later, hearts were isolated and subjected to 40 min ischemia and 30 min reperfusion (I/R). The effect of DE and other interventions on hemodynamic, terminal dUTP nick-end labeling staining and biochemical changes during I/R was assessed in mouse hearts. Treatment with DE resulted in a 2.2-fold increase in phosphorylation of Akt and a significant increase in eNOS and inducible NOS (iNOS) proteins. Akt is upstream of NOS and the mitoKATP channel as simultaneous pretreatment of WTN with DE abolished phosphorylation of Akt, which was not affected by l-NAME and 5-hydroxydecanoate. In hearts treated with DE, cardiac function was significantly improved after I/R, and apoptosis was also significantly decreased. WTN abolished the antiapoptotic effect of DE. Similarly, S-methylisothiourea, a specific iNOS inhibitor, when given to eNOS−/− mice that were pretreated with DE completely abolished the beneficial effects of DE on reduction of apoptotic death. DE was partially effective in eNOS−/− mice against the ischemic injury. It is concluded that DE activates Akt through the PI3 kinase signaling pathway and iNOS and eNOS is downstream of Akt.

scholarly journals ACSL1 Inhibits ALV-J Replication by IFN-Ⅰ Signaling and PI3K/Akt Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Qihong Zhang ◽  
Tingting Xie ◽  
Guodong Mo ◽  
Zihao Zhang ◽  
Ling Lin ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Akt Signaling ◽  
Akt Pathway ◽  
Akt Signaling Pathway ◽  
Hematopoietic Malignancy ◽  
Interferon Stimulated Genes ◽  
Primary Monocyte ◽  
Chain Acyl ◽  
Underlying Mechanisms ◽  
Long Chain

J subgroup avian leukosis virus (ALV-J) infection causes serious immunosuppression problems, leading to hematopoietic malignancy tumors in chicken. It has been demonstrated that interferon-stimulated genes (ISGs) could limit ALV-J replication; nevertheless, the underlying mechanisms remain obscure. Here, we demonstrate that Long-chain Acyl-CoA synthetase 1 (ACSL1) is an interferon (IFN)-stimulated gene that specifically restricts the replication of ALV-J due to the higher IFN-I production. More importantly, ACSL1 induces primary monocyte-derived macrophages (MDMs) to pro-inflammatory phenotypic states during ALV-J infection, and ACSL1 mediates apoptosis through the PI3K/Akt signaling pathway in ALV-J-infected primary monocyte-derived macrophages (MDMs). Overall, these results provide evidence that ACSL1 contributes to the antiviral response against ALV-J.

scholarly journals Integrated Genomic Analysis Highlights the Impaired PI3K-Akt Signaling Pathway in Alzheimer’s Disease

2021 ◽  
Vol 12 (2) ◽  
pp. 2332-2339
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Signaling Pathway ◽  
Meta Analysis ◽  
Temporal Cortex ◽  
Genomic Analysis ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Underlying Mechanisms ◽  
Treatment And Diagnosis

Alzheimer’s disease (AD), a leading cause of dementia, remained incurable, despite many advances in our knowledge about AD pathogenesis, underlying mechanisms are poorly understood. Transcriptome analysis showed efficiency in exploring these mechanisms; however, data are generated at a higher pace than interpreted and are almost inconsistent. Therefore we performed this meta-analysis to extract new knowledge from existing data and find the mechanisms involved in AD. Five temporal cortex transcriptomics datasets from 187 AD patients and 167 healthy controls were analyzed. Our analysis showed that the PI3K-Akt signaling pathway is significantly impaired in AD brains and was common among all datasets. Moreover, miRs targeting genes involved in the PI3K-Akt signaling pathway were identified. In conclusion, our results highlight the impaired PI3K-Akt signaling pathway in AD and suggested related miRs as the potential targets for early treatment and diagnosis of AD.

scholarly journals Tizanidine hydrochloride exhibits a cytotoxic effect on osteosarcoma cells through the PI3K/AKT signaling pathway

2019 ◽  
Vol 47 (8) ◽  
pp. 3792-3802
Author(s):  
Xue-Wu Xing ◽  
Yu-Fu Sun ◽  
Jun Zhao ◽  
Zi-Xiang Pan ◽  
Wen-Xue Jiang
Keyword(s):  
Signaling Pathway ◽  
Adrenergic Receptors ◽  
Akt Signaling ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Akt Signaling Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Expression Levels ◽  
Underlying Mechanisms

Objectives α2-adrenergic receptors are reportedly involved in cancer cell proliferation, invasion, and apoptosis through regulation of diverse molecules, which implies that it contributes to tumor progression. However, the functional significance of α2-adrenergic receptors in osteosarcoma (OS) is unclear. Tizanidine hydrochloride (THC), an α2-adrenergic receptor agonist, is often used to alleviate symptoms of spasticity. This study investigated the functional implications of THC treatment on human OS cells and the underlying mechanisms of resulting changes. Methods The proliferation of U2 OS cells was assessed by Cell Counting Kit-8; the migration and invasion capacities of U2 OS cells were then analyzed by transwell assay. Moreover, apoptosis in U2 OS cells was evaluated by flow cytometry and western blot analyses. Additionally, expression levels of key proteins in the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway were measured. Results THC inhibited the proliferation, migration, and invasion of U2 OS cells, but promoted apoptosis within these cells. Expression levels of p-AKT, p-mTOR, and p-P70S6K were reduced by exposure to THC, suggesting involvement of PI3K/AKT signaling in THC-induced cytotoxicity within OS cells. Conclusions THC may play a novel role in OS cell cytotoxicity, and these findings suggest a potent therapeutic strategy for OS treatment.

scholarly journals Administration of rCTRP9 Attenuates Neuronal Apoptosis Through AdipoR1/PI3K/Akt Signaling Pathway after ICH in Mice

2019 ◽  
Vol 28 (6) ◽  
pp. 756-766 ◽  
Author(s):  
Lianhua Zhao ◽  
John H. Zhang ◽  
Prativa Sherchan ◽  
Paul R. Krafft ◽  
Wei Zhao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Neuronal Apoptosis ◽  
Molecular Mechanisms ◽  
Neuroprotective Effect ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Western Blots ◽  
Short And Long Term ◽  
Underlying Mechanisms

Targeting neuronal apoptosis after intracerebral hemorrhage (ICH) may be an important therapeutic strategy for ICH patients. Emerging evidence indicates that C1q/TNF-Related Protein 9 (CTRP9), a newly discovered adiponectin receptor agonist, exerts neuroprotection in cerebrovascular disease. The aim of this study was to investigate the anti-apoptotic role of CTRP9 after experimental ICH and to explore the underlying molecular mechanisms. ICH was induced in mice via intrastriatal injection of bacterial collagenase. Recombinant CTRP9 (rCTRP9) was administrated intranasally at 1 h after ICH. To elucidate the underlying mechanisms, adiponectin receptor1 small interfering ribonucleic acid (AdipoR1 siRNA) and selective PI3 K inhibitor LY294002 were administered prior to rCTRP9 treatment. Western blots, neurofunctional assessments, immunofluorescence staining, and Fluoro-Jade C (FJC) staining experiments were performed. Administration of rCTRP9 significantly improved both short- and long-term neurofunctional behavior after ICH. RCTRP9 treatment significantly increased the expression of AdipoR1, PI3 K, p-Akt, and Bcl-2, while at the same time was found to decrease the expression of Bax in the brain, which was reversed by inhibition of AdipoR1 and PI3 K. The neuroprotective effect of rCTRP9 after ICH was mediated by attenuation of neuronal apoptosis via the AdipoR1/PI3K/Akt signaling pathway; therefore, rCTRP9 should be further evaluated as a potential therapeutic agent for ICH patients.

scholarly journals Cardiac Shock Wave Therapy Improves Ventricular Function by Relieving Fibrosis Through PI3K/Akt Signaling Pathway: Evidence From a Rat Model of Post-infarction Heart Failure

2021 ◽  
Vol 8 ◽  
Author(s):  
Luqiao Wang ◽  
Xin Tian ◽  
Yuting Cao ◽  
Xuejuan Ma ◽  
Leilei Shang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Shock Wave ◽  
Cardiac Function ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Shock Wave Therapy ◽  
Beneficial Effects ◽  
Cardiac Shock ◽  
Cardiac Shock Wave Therapy

Objection: Cumulative studies have identified the effectiveness of cardiac shock wave therapy (CSWT) in treating heart failure after acute myocardial infarction (AMI), but little have been discussed with regard to the beneficial effects of CSWT on anti-fibrosis along with the underlying mechanism. In this study, we investigated whether CSWT could reduce post-AMI fibrosis and further explored the molecular mechanism.Methods: Rat heart failure (HF) models induced by ligating the left anterior descending coronary artery were established and validated by echocardiography. Eligible animals were randomly categorized into five groups: the sham group, the HF group, the HF + CSWT group, the HF + LY294002 group, and the HF + CSWT + LY294002 group. The cardiac weight, serum level of BNP, NT-pro BNP and echocardiography parameters were measured to assess cardiac function in different groups. Masson's trichrome staining was used to assess the proportions of the fibrotic area. The expression level of CD34, αSMA was measured by RT-PCR, Immunohistochemistry and Immunofluorescent analyses and the level of PI3K/Akt was quantified by Immunohistochemistry and Western blotting.Results: The application of CSWT significantly improved cardiac function and reduced myocardial fibrosis and level of CD34 and αSMA, compared to the HF group. CSWT led to significant elevations of p-PI3K and p-Akt expression levels compared to that of the HF group and the inhibition of the PI3K/Akt pathway abolished the observed beneficial effects of CSWT.Conclusion: CSWT can facilitate the alleviation of cardiac fibrosis induced by AMI through the activation of PI3K/Akt signaling pathway.

scholarly journals Luteolin Ameliorates Experimental Pulmonary Arterial Hypertension via Suppressing Hippo-YAP/PI3K/AKT Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Wanyun Zuo ◽  
Na Liu ◽  
Yunhong Zeng ◽  
Zhenghui Xiao ◽  
Keke Wu ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Flavonoid Compound ◽  
Dependent Manner ◽  
Akt Signaling Pathway ◽  
Pulmonary Arterial ◽  
Underlying Mechanisms ◽  
And Migration

Luteolin is a flavonoid compound with a variety of pharmacological effects. In this study, we explored the effects of luteolin on monocrotaline (MCT) induced rat pulmonary arterial hypertension (PAH) and underlying mechanisms. A rat PAH model was generated through MCT injection. In this model, luteolin improved pulmonary vascular remodeling and right ventricular hypertrophy, meanwhile, luteolin could inhibit the proliferation and migration of pulmonary artery smooth muscle cells induced by platelet-derived growth factor-BB (PDGF-BB) in a dose-dependent manner. Moreover, our results showed that luteolin could downregulate the expression of LATS1 and YAP, decrease YAP nuclear localization, reduce the expression of PI3K, and thereby restrain the phosphorylation of AKT induced by PDGF-BB. In conclusion, luteolin ameliorated experimental PAH, which was at least partly mediated through suppressing HIPPO-YAP/PI3K/AKT signaling pathway. Therefore, luteolin might become a promising candidate for treatment of PAH.

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