Dataset Information

Soy Isoflavones Protect Neuronal PC12 Cells against Hypoxic Damage through Nrf2 Activation and Suppression of p38 MAPK and AKT-mTOR Pathways.

ABSTRACT: Isoflavones are a class of major phenolic compounds, derived from soybeans, that possess unique therapeutic and biological properties. The possible mechanisms of isoflavone-mediated protection of neuronal PC12 cells against hypoxic damage was investigated in this study. Isoflavones showed potential neuroprotective effects by increasing cell viability, decreasing the level of reactive oxygen species (ROS), and inhibiting apoptosis and cell cycle arrest in cobalt chloride (CoCl₂)-induced hypoxic damage. A Western blot analysis indicated that isoflavones decreased apoptosis by up-regulating the Bcl-xL protein and down-regulating the Bax protein. They further reduced the S-phase fraction of the cell cycle by down-regulating the p21 protein and up-regulating the cyclin A protein levels. Additionally, isoflavones activated Nrf2 protein translocation and inhibited the p38 MAPK and AKT-mTOR pathways. A molecular docking analysis further revealed that isoflavones displayed a potential competitive interaction with the Nrf2 protein for Keap1. Our findings suggest that isoflavones could be a potent neuroprotective phytochemical in soybeans and their products.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC9598610 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Soy Isoflavones Protect Neuronal PC12 Cells against Hypoxic Damage through Nrf2 Activation and Suppression of p38 MAPK and AKT-mTOR Pathways.

Zhang Yongzhu Y Yin Liqing L Dong Jiajia J Xia Xiudong X

Antioxidants (Basel, Switzerland) 20221016 10

Isoflavones are a class of major phenolic compounds, derived from soybeans, that possess unique therapeutic and biological properties. The possible mechanisms of isoflavone-mediated protection of neuronal PC12 cells against hypoxic damage was investigated in this study. Isoflavones showed potential neuroprotective effects by increasing cell viability, decreasing the level of reactive oxygen species (ROS), and inhibiting apoptosis and cell cycle arrest in cobalt chloride (CoCl<sub>2</sub>)-induce ...[more]

PMID: 36290760

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Project description:Background and aimsAssociations between soy intake and risk of cancer have been evaluated in prospective observational studies with inconsistent results. Whether the potential anticancer effects offered by soy were attributed to soy isoflavones and soy protein still needs to be elucidated. This study aimed to comprehensively quantify the association of soy, soy isoflavones and soy protein intake with risk of cancer incidence and cancer mortality by conducting a meta-analysis of all available studies.MethodsPubMed, Embase, Web of Science, and Cochrane Library databases were searched up to 16 September 2021. Prospective cohort studies that examined the effect of soy, soy isoflavones and soy protein on cancer incidence and cancer mortality were identified. Random-effects models were used to pool the multivariable-adjusted relative risks (RRs) and corresponding 95% confidence intervals (CIs). The potential dose-response relations were explored by using generalized least-squares trend estimation.ResultsEighty one prospective cohort studies were included in the meta-analysis. A higher intake of soy was significantly associated with a 10% reduced risk of cancer incidence (RR, 0.90; 95% CI, 0.83-0.96). Each additional 25 g/d soy intake decreased the risk of cancer incidence by 4%. Intake of soy isoflavones was inversely associated with risk of cancer incidence (RR, 0.94; 95% CI, 0.89-0.99), whereas no significant association was observed for soy protein. The risk of cancer incidence was reduced by 4% with each 10 mg/d increment of soy isoflavones intake. Similar inverse associations were also found for soy in relation to site-specific cancers, particularly lung cancer (RR, 0.67; 95%CI, 0.52-0.86) and prostate cancer (RR, 0.88; 95%CI, 0.78-0.99). However, high intake of soy, soy isoflavones and soy protein were not associated with cancer mortality.ConclusionsHigher intake of soy and soy isoflavones were inversely associated with risk of cancer incidence, which suggested that the beneficial role of soy against cancer might be primarily attributed to soy isoflavones. These findings support recommendations to include soy as part of a healthy dietary pattern for the prevention of cancer.

Project description:BackgroundHypoxic pulmonary hypertension (HPH) is a chronic progressive advanced disorder pathologically characterized by pulmonary vascular remodeling. Notch4 as a cell surface receptor is critical for vascular development. However, little is known about the role and mechanism of Notch4 in the development of hypoxic vascular remodeling.MethodsLung tissue samples were collected to detect the expression of Notch4 from patients with HPH and matched controls. Human pulmonary artery smooth muscle cells (HPASMCs) were cultured in hypoxic and normoxic conditions. Real-time quantitative PCR and western blotting were used to examine the mRNA and protein levels of Notch4. HPASMCs were transfected with small interference RNA (siRNA) against Notch4 or Notch4 overexpression plasmid, respectively. Cell viability, cell proliferation, apoptosis, and migration were assessed using Cell Counting Kit-8, Edu, Annexin-V/PI, and Transwell assay. The interaction between Notch4 and ERK, JNK, P38 MAPK were analyzed by co-immunoprecipitation. Adeno-associated virus 1-mediated siRNA against Notch4 (AAV1-si-Notch4) was injected into the airways of hypoxic rats. Right ventricular systolic pressure (RVSP), right ventricular hypertrophy and pulmonary vascular remodeling were evaluated.ResultsIn this study, we demonstrate that Notch4 is highly expressed in the media of pulmonary vascular and is upregulated in lung tissues from patients with HPH and HPH rats compared with control groups. In vitro, hypoxia induces the high expression of Delta-4 and Notch4 in HPASMCs. The increased expression of Notch4 promotes HPASMCs proliferation and migration and inhibits cells apoptosis via ERK, JNK, P38 signaling pathways. Furthermore, co-immunoprecipitation result elucidates the interaction between Notch4 and ERK/JNK/P38. In vivo, silencing Notch4 partly abolished the increase in RVSP and pulmonary vascular remodeling caused by hypoxia in HPH rats.ConclusionsThese findings reveal an important role of the Notch4-ERK/JNK/P38 MAPK axis in hypoxic pulmonary remodeling and provide a potential therapeutic target for patients with HPH.

Dataset Information

Soy Isoflavones Protect Neuronal PC12 Cells against Hypoxic Damage through Nrf2 Activation and Suppression of p38 MAPK and AKT-mTOR Pathways.

Publications

Soy Isoflavones Protect Neuronal PC12 Cells against Hypoxic Damage through Nrf2 Activation and Suppression of p38 MAPK and AKT-mTOR Pathways.

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