INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Pingchuan Wang,Tianming Li,Changping Niu,Siyu Sun,Dongyan Liu
Reactive oxygen species (ROS) damage to the intestinal barrier is a side effect of prolonged hyperoxia therapy in neonates, which impairs growth and development of the intestine and promotes intestinal diseases. However, the research on clinical prevention and treatment is lacking. Therefore, we investigated the molecular mechanisms of the neonate intestinal response against hyperoxia-derived ROS to find targets for intestinal barrier damage prevention. Human intestinal epithelial cells were incubated under hyperoxia (85% oxygen) to build an in vitro model. ROS and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway were inhibited to detect the MAPK/ERK pathway, nuclear factor erythroid factor 2-related factor 2 (Nrf2), hypoxia-inducible factor-1α (Hif-1α), and interleukin-17D (IL-17D) expression. Nrf2 was inhibited to detect Hif-1α and IL-17D expression. Hif-1α was inhibited to detect Nrf2, IL-17D, and tight junction proteins expression and apoptosis. Cells were treated with human recombinant IL-17D to detect TNF-α, IL-1β, IL-10, and tight junction proteins expression. ROS, Nrf2, Hif-1α, and IL-17D were upregulated and the MAPK/ERK pathway was activated under hyperoxia. But ROS inhibition downregulated the MAPK/ERK pathway, Nrf2, Hif-1α, and IL-17D. MAPK/ERK pathway inhibition downregulated Nrf2, Hif-1α, and IL-17D. Nrf2 inhibition downregulated Hif-1α and IL-17D. Hif-1α inhibition downregulated Nrf2, IL-17D, tight junction proteins, and exacerbated apoptosis. The recombinant IL-17D downregulated TNF-α, IL-1β, but upregulated IL-10 and tight junction proteins. We concluded that Hyperoxia-generated ROS activated the MAPK/ERK pathway to regulate Nrf2, Hif-1α, and IL-17D expression. Nrf2 and Hif-1α were interdependent and promoted IL-17D. Importantly, Hif-1α and IL-17D expression protected the intestinal epithelial barrier.
研究领域:
分子生物学
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细胞生物学
·
儿科
·
肠道生理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
·
2019
·Vol. 235
·期 3
·2847-2856
·
IF 4.522
Jiabing Zhang,Leili Wang,Wei Xie,Shunying Hu,Hao Zhou,Pingjun Zhu,Hang Zhu
Septic cardiomyopathy is associated with mitochondrial damage and endoplasmic reticulum (ER) dysfunction. However, the upstream mediator of mitochondrial injury and ER stress has not been identified and thus little drug is available to treat septic cardiomyopathy. Here, we explored the role of B-cell receptor-associated protein 31 (BAP31) in septic cardiomyopathy and figure out whether melatonin could attenuate sepsis-mediated myocardial depression via modulating BAP31. Lipopolysaccharide (LPS) was used to establish the septic cardiomyopathy model. Pathway analysis was performed via western blot, quantitative polymerase chain reaction and immunofluorescence. Mitochondrial function and ER stress were detected via enzyme-linked immunosorbent assay, western blot, and immunofluorescence. After exposure to LPS, cardiac function was reduced due to excessive inflammation response and extensive cardiomyocyte death. Mechanistically, melatonin treatment could dose-dependently improve cardiomyocyte viability via preserving mitochondrial function and reducing ER stress. Further, we found that BAP31 transcription was repressed by LPS whereas melatonin could restore BAP31 expression; this effect was dependent on the MAPK-ERK pathway. Inhibition of the ERK pathway and/or knockdown of BAP31 could attenuate the beneficial effects of melatonin on mitochondrial function and ER homeostasis under LPS stress. Altogether, our results indicate that ERK-BAP31 pathway could be used as a critical mediator for mitochondrial function and ER homeostasis in sepsis-related myocardial injury. Melatonin could stabilize BAP31 via the ERK pathway and thus contribute to the preservation of cardiac function in septic cardiomyopathy.
研究领域:
心脏病学
·
药理学
·
分子生物学
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DOI
PubMed
高影响因子
Biochemistry and Biophysics Reports
·
2025
·
IF 2.2
Haipeng Feng,Qianqian Qiao,Jingyan Zhang,Kang Zhang,Lei Wang,Jianxi Li
Duchesnea indica (Andr.) Focke ( DIF ), a medicinal plant from the Rosaceae family, possesses therapeutic properties such as heat-clearing and detoxification, dispersion of stasis detumescence, blood-cooling, and hemostatic effect. The latest research unveiled a diverse array of pharmacologically active compounds from DIF, showcasing a broad spectrum of pharmacological effects. However, there was limited attention given to the comprehensive investigation of its high molecular weight compounds, particularly polysaccharides. In this study, DIF extracts were prepared by water-extraction and alcohol-precipitation method and the pharmacological effect was detected. The results demonstrated that the total polysaccharide content, reducing sugar content, total flavonoid content, and total polyphenol content in DIF extracts were 32.62 ± 0.91 %, 13.41 ± 0.18 %, 1.07 ± 0.07 %, and 12.16 ± 0.27 %, respectively. Although the total antioxidant activity of DIF extracts were significantly low than that of the vitamin C group, its ability to scavenge ABTS, DPPH, and superoxide anion radicals was similar to that of the vitamin C group. Furthermore, DIF extracts demonstrated significant inhibition on NO and MDA levels while simultaneously enhancing SOD activity in LPS-stimulated RAW264.7 cells. Finally, DIF extracts significantly reduced the mRNA level of pro-inflammation cytokines interleukin ( IL )-6, IL-1β, inducible nitric oxide synthase ( iNOS ), cyclooxygenase-2 ( COX-2 ) and tumor necrosis factor ( TNF ) -α , and directly inhibited the phosphorylation level of extracellular regulated kinase and mitogen-activated protein kinase ( ERK-MAPK ) pathway. Taken together, these results indicated that DIF extracts exhibited an anti-inflammatory and antioxidant effect in LPS-induced RAW264.7 mouse macrophages by directly inhibiting ERK-MAPK signaling pathway. Based on these findings, DIF extracts provided new insights into the treatment and prevention of diseases related to oxidative stress and inflammation.
研究领域:
药理学
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免疫学
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天然产物化学
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分子生物学
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炎症与感染
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抗氧化研究
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信号转导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2023
·Vol. 30
·期 32
·79423-79436
·
IF 5.8
Zhang Jingni,Wang Hongjuan,Chen Huan,Liu Yong,Wang An,Hou Hongwei,Hu Qingyuan
Long-term use of alcohol and cigarettes is associated with millions of deaths each year, directly or indirectly. The carcinogen acetaldehyde is both a metabolite of alcohol and the most abundant carbonyl compound in cigarette smoke, and co-exposure of them is usual and primarily leads to liver and lung injury, respectively. However, few studies have explored the synchronic risk of acetaldehyde on the liver and lung. Here, we investigated the toxic effects and related mechanisms of acetaldehyde based on normal hepatocytes and lung cells. The results showed that acetaldehyde caused significant dose-dependent increases of cytotoxicity, ROS level, DNA adduct level, DNA single/double-strand breakage, and chromosomal damage in BEAS-2B cells and HHSteCs, with similar effects at the same doses. The gene and protein expression and phosphorylation of p38MAPK, ERK, PI3K, and AKT, key proteins of MAPK/ERK and PI3K/AKT pathways regulating cell survival and tumorigenesis, were significantly upregulated on BEAS-2B cells, while only protein expression and phosphorylation of ERK were upregulated significantly, the other three decreased in HHSteCs. When either the inhibitor of the four key proteins was co-treated with acetaldehyde, cell viabilities were almost unchanged in BEAS-2B cells and HHSteCs. Thus, acetaldehyde could synchronically induce similar toxic effects in BEAS-2B cells and HHSteCs, and MAPK/ERK and PI3K/AKT pathways seem to be involved in different regulatory mechanisms.
研究领域:
毒理学
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细胞生物学
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分子生物学
·
致癌机制
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产品关联
DOI
PubMed
高影响因子
Human Cell
·
2024
·
IF 3.4
Guo Xiaoli,Cao Yijuan,He Qing,Chen Linna,Wang Qing,Zhang Jingbo,Lv Wenqiang,Zhang Bei,Zhou Xueyan
Polycystic ovary syndrome (PCOS) is a complex gynaecological endocrine disease that occurs in women of childbearing age. The pathogenesis of PCOS is still unclear and further exploration is needed. Here, proteomic analysis indicated that the expression of farnesyl diphosphate synthase (FDPS) protein in ovarian tissue of PCOS mice was significantly decreased. The purpose of this study is to investigate the relationship between potential biomarkers of PCOS and granulosa cells (GCs) function. The mechanisms by which FDPS affected the proliferation of granulosa cells were also explored both in vitro and in vivo. We found that knockdown of FDPS inhibited the proliferation of KGN (human ovarian granulosa cell line), while overexpression of FDPS had the opposite effect. FDPS activated Rac1 (Rac Family Small GTPase 1) activity and regulated MAPK/ERK signalling pathway, which affecting the proliferation of KGN cells significantly. In addition, treatment with the adeno-associated virus (AAV)-FDPS reverses the dehydroepiandrosterone (DHEA)-induced PCOS-phenotype in mice. Our data indicated that FDPS could regulate the proliferation of ovarian GCs by modulating MAPK/ERK (mitogen-activated protein kinase/extracellular regulated protein kinases) pathway via activating Rac1 activity. These findings suggest that FDPS could be of great value for the regulation of ovarian granulosa cell function and the treatment of PCOS.
研究领域:
妇科学
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内分泌学
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分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2021
·Vol. 47
·期 6
·1-10
·
IF 4.101
Xinyan Ma,Ying Zhang,Mingyang Guan,Weidong Zhang,Huifang Tian,Caixiao Jiang,Xiaoxin Tan,Weijun Kang
The toxicity of chloroacetamide herbicide in embryo development remains unclear. Acetochlor (AC) is a chloroacetamide that metabolizes into 2‑ethyl‑6‑methyl-2-chloroacetanilide (CMEPA) and 6‑ethyl‑o‑toluidine (MEA). The present study determined the potential effect of AC and its metabolites on embryo development. Both HepG2 cells and zebrafish embryos were exposed to AC, CMEPA and MEA in the presence or absence of co‑treatment with anti‑reactive oxygen species (ROS) reagent N‑acetylcysteine. The generation of ROS, levels of superoxide dismutase (SOD) and glutathione (GSH) in HepG2 cells and lactate dehydrogenase (LDH) leakage from HepG2 cells were investigated. The effects of AC, CMEPA and MEA on DNA breakage, MAPK/ERK pathway activity, viability and apoptosis of HepG2 cells were examined by comet assay, western blotting, MTT assay and flow cytometry, respectively. Levels of LDH, SOD and GSH in zebrafish embryos exposed to AC, CMEPA and MEA were measured. The hatching and survival rates of zebrafish embryos exposed to AC, CMEPA and MEA, were determined, and apoptosis of hatched fish was investigated using acridine orange staining. The present data showed AC, CMEPA and MEA induced generation of ROS and decreased levels of SOD and GSH in HepG2 cells, which in turn promoted DNA breakage and LDH leakage from cells, ultimately inhibiting cell viability and inducing apoptosis, as well as phosphorylation of JNK and P38. However, co‑treatment with N‑acetylcysteine alleviated the pro‑apoptosis effect of AC and its metabolites. Moreover, exposure to AC, CMEPA and MEA lead to toxicity of zebrafish embryos with decreased SOD and GSH and increased LDH levels and cell apoptosis, ultimately decreasing the hatching and survival rates of zebrafish, all of which was attenuated by treatment with N‑acetylcysteine. Therefore, AC and its metabolites (CMEPA and MEA) showed cytotoxicity and embryo development toxicity.
研究领域:
毒理学
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分子生物学
·
发育生物学
·
环境科学
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DOI
PubMed
高影响因子
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