Deficiency in Neuroserpin Exacerbates CoCl2 Induced Hypoxic Injury in the Zebrafish Model by Increased Oxidative Stress

Sha, Han; Zhang, Dongyang; Dong, Qiang; Wang, Xu; Wang, Liang

doi:10.3389/fphar.2021.632662

Cited by 13 publications

(6 citation statements)

References 51 publications

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“…In our experiment, we observed the location of Nrf2 protein by laser confocal microscope, and found that Nrf2 protein exists in the cytoplasm of hippocampal neuronal cells under normoxia state, while neuronal cells undergo oxidative stress under hypoxia state after CoCl2 treatment. These results were consistent with previous studies 37 . In addition, our results showed that Nrf2 protein enters the nucleus, and the level of ROS increases significantly, which is similar with some researches 38 .…”

Section: Discussionsupporting

confidence: 94%

Imperatorin exerts antioxidant effects in vascular dementia via the Nrf2 signaling pathway

Liao

Min

Zhong

et al. 2023

Sci Rep

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Imperatorin, an active ingredient extracted from Angelica and Qianghuo, has anti-inflammatory, anti-oxidative stress damage, blocking calcium channels, and other properties. Our preliminary findings revealed the protective role of imperatorin in the treatment of vascular dementia, we further explored the underlying mechanisms concerning the neuroprotection function of imperatorin in vascular dementia. The cobalt chloride (COCl2)-induced chemical hypoxia and hypoglycemia of hippocampal neuronal cells was applied as in vitro vascular dementia model. Primary neuronal cells was isolated from the hippocampal tissue of SD suckling rats within 24 h of birth. Hippocampal neurons were identified by immunofluorescence staining of microtubule-associated protein 2. Silencing or overexpression of Nrf2 was conducted by transfection of corresponding plasmids in hippocampal neuronal cells. Cell viability was detected by MTT assay to determine the optimal modeling concentration of CoCl2. Mitochondrial membrane potential, intracellular reactive oxygen species and apoptosis rate was measured by flow cytometry. The expression of anti-oxidative proteins was detected by quantitative real-time PCR and western blot, including Nrf2, NQO-1 and HO-1. Nrf2 nuclear translocation was detected using laser confocal microscopy. The modeling concentration of CoCl2 was 150umol/l, and the best interventional concentration of imperatorin was 7.5umol/l. Significantly, imperatorin facilitated the nuclear localization of Nrf2, promoted the expressions of Nrf2, NQO-1, and HO-1 relative to the model-control group. Moreover, imperatorin reduced the mitochondrial membrane potential and ameliorated CoCl2-induced hypoxic apoptosis in hippocampal neurons. On the contrary, silencing Nrf2 completely abrogated the protective effects of imperatorin. Imperatorin might be an effective drug for preventing and treating vascular dementia.

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Section: Discussionsupporting

confidence: 94%

Imperatorin exerts antioxidant effects in vascular dementia via the Nrf2 signaling pathway

Liao

Min

Zhong

et al. 2023

Sci Rep

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“…Such phenotype was observed on knockdown of jnk2 morpholino, which resulted in 9% of the embryos displaying a complete lack of a tail. The hypoxia‐inducing effect of CoCl 2 in zebrafish is evident from several studies and results in increased expression of angiogenesis and its growth factors (Han et al, 2021; Vivek et al, 2015; Wu et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Noscapine modulates hypoxia‐induced angiogenesis and hemodynamics: Insights from a zebrafish model investigation

Nathan,

Shameera,

Sivakumar

et al. 2024

Drug Development Research

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We investigated the angiogenesis‐modulating ability of noscapine in vitro using osteosarcoma cell line (MG‐63) and in vivo using a zebrafish model. MTT assay and the scratch wound healing assay were performed on the osteosarcoma cell line (MG‐63) to analyze the cytotoxic effect and antimigrative ability of noscapine, respectively. We also observed the antiangiogenic ability of noscapine on zebrafish embryos by analyzing the blood vessels namely the dorsal aorta, and intersegmental vessels development at 24, 48, and 72 h postfertilization. Real‐time polymerase chain reaction was used to analyze the hypoxia signaling molecules' gene expression in MG‐63 cells and zebrafish embryos. The findings from the scratch wound healing demonstrated that noscapine stopped MG‐63 cancer cells from migrating under both hypoxia and normoxia. Blood vessel development and the heart rate in zebrafish embryos were significantly reduced by noscapine under both hypoxia and normoxia which showed the hemodynamics impact of noscapine. Noscapine also downregulated the cobalt chloride (CoCl2) induced hypoxic signaling molecules' gene expression in MG‐63 cells and zebrafish embryos. Therefore, noscapine may prevent MG‐63 cancer cells from proliferating and migrating, as well as decrease the formation of new vessels and the production of growth factors linked to angiogenesis in vivo under both normoxic and hypoxic conditions.

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“…Cells were then subcultured or inoculated into 96-well plates according to experimental design. Cobalt chloride (CoCl 2 ) is used as a common chemical hypoxic agent to simulate hypoxic/ischemic conditions in a variety of cells (Pecoraro, Pinto, & Popolo, 2018;Han, Zhang, Dong, Wang, & Wang, 2021). Based on the results of the CCK-8 assay, Nar and CoCl 2 concentrations were determined.…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

The cardioprotective effects and mechanisms of naringenin in myocardial ischemia based on network pharmacology and experiment verification

Yang

Chen

et al. 2022

Front. Pharmacol.

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Naringenin (Nar) is a natural flavonoid extracted from citrus fruits with abundant pharmacological properties against cardiac diseases, but existing studies are unsystematic and scattered. The present research systematically investigates the mechanism of action of Nar in the treatment of myocardial ischemia (MI). Network pharmacology was used to analyze the relevant targets of Nar against MI as well as the biological mechanisms. The protective effect of Nar was initially assessed in H9c2 cells induced by CoCl2. In acutely isolated rat cardiomyocytes, Nar was further explored for effects on L-type Ca2+ currents, cell contractility and Ca2+ transients by using patch-clamp technique and Ion Optix system. Network pharmacology analysis indicated that Nar improved apoptosis, mitochondrial energy metabolism, inflammation and oxidative stress. Experimental validation demonstrated that Nar decreased ROS and MDA levels and increased antioxidant activity (e.g., GSH-PX, SOD, and CAT), mitochondrial membrane potential, ATP and Ca2+-ATPase contents. Nar also markedly reduced inflammatory factor levels, apoptosis, and intracellular Ca2+ concentrations in H9c2 cells. Based on the experimental results, it is speculated that Ca2+ signals play an essential role in the process of Nar against MI. Thus, we further confirmed that Nar significantly inhibited the L-type Ca2+ currents, contractility and Ca2+ transients in acutely isolated cardiomyocytes. The inhibition of Ca2+ overload by Nar may be a novel cardioprotective mechanism. The present study may serve as a basis for future clinical research, and Nar as a Ca2+ channel inhibitor may provide new perspectives for the treatment of myocardial ischemic diseases.

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Deficiency in Neuroserpin Exacerbates CoCl2 Induced Hypoxic Injury in the Zebrafish Model by Increased Oxidative Stress

Cited by 13 publications

References 51 publications

Imperatorin exerts antioxidant effects in vascular dementia via the Nrf2 signaling pathway

Imperatorin exerts antioxidant effects in vascular dementia via the Nrf2 signaling pathway

Noscapine modulates hypoxia‐induced angiogenesis and hemodynamics: Insights from a zebrafish model investigation

The cardioprotective effects and mechanisms of naringenin in myocardial ischemia based on network pharmacology and experiment verification

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