FOOD RESEARCH INTERNATIONAL
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2014
·
IF 3.05
Cunliu Zhou,Huiqiong Ye,Tadayuki Nishiumi,Hao Qin,Conggui Chen
The objective of this investigation was to evaluate the effects of l -histidine on the stability of porcine hemoglobin concentrates during storage. The results indicated that the addition of l -histidine increased the oxyhemoglobin content and a* values but decreased the methemoglobin content and free iron content (P < 0.05) during storage. The addition of iron cation decreased both the oxyhemoglobin content and a* values but increased both the methemoglobin content and free iron concentration (P < 0.05). CD spectra revealed that the free iron content induced the transformation of the hemoglobin secondary structure from an α-helix (close structure) to a β-pleated, β-turn, and random coil arrangement (loose structure), while l -histidine weakened this behavior of the free iron. Infrared spectra demonstrated that the l -histidine coordinated with the free iron (Fe 2 + or Fe 3 + ) to give the corresponding complex at 25 °C and pH 7.3. Therefore, l -histidine enhanced the stability of hemoglobin concentrates by coordinating with free iron.
研究领域:
生物化学
·
医学工程
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DOI
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2022
·
IF 3.322
Xuan Ma,Hui Chen,Lixing Cao,Shuang Zhao,Chong Zhao,Shutao Yin,Lihong Fan,Hongbo Hu
Ferroptosis is a new form of iron-dependent cell death . A growing body of evidence suggests that abnormal ferroptosis is involved in developing neurodegenerative diseases. 18β-glycyrrhetinic acid (GA) is a major bioactive component of licorice with multiple biological activities including neuroprotection. Give the role of ferroptosis in the neurodegenerative diseases, we hypothesized that the neuroprotective effect of GA might be associated with its ability to protect neuro-cells from ferroptosis. Results demonstrated that GA was able to prevent a well-known ferroptosis inducer ferroptosis inducer 56 (FIN56)-triggered ferroptosis in HT22 mouse neuronal cell. Further mechanistic investigation revealed that the protection of GA on ferroptosis is attributed its inhibiting effect on cellular labile iron accumulation and up-regulating coenzyme Q10 (CoQ10) levels. The findings of the present study uncovered a novel mechanism involved in the neuroprotective effect of GA, and imply that GA could be developed as a novel agent to manage ferroptosis-related diseases.
研究领域:
神经科学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2024
·
IF 4.7
Yan-Ting Lv,Tian-Bin Liu,Yue Li,Zhen-Yong Wang,Cai-Yu Lian,Lin Wang
Cadmium (Cd), a prevalent environmental contaminant, has attracted widespread attention due to its serious health hazards. Ferroptosis is a form of iron-dependent oxidative cell death that contributes to the development of various kidney diseases. However, the mechanisms underlying the occurrence of ferroptosis in Cd-induced renal tubular epithelial cells (TECs) have not been fully elucidated. Hereby, both in-vitro and in-vivo experiments were established to elucidate this issue. In this study, we found that Cd elicited accumulation of lipid peroxides due to intracellular ferrous ion (Fe 2+ ) overload and glutathione depletion, contributing to ferroptosis. Inhibition of ferroptosis via chelation of Fe 2+ or reduction of lipid peroxidation can significantly mitigate Cd-induced cytotoxicity. Renal transcriptome analysis revealed that the activation of heme oxygenase 1 (HO-1) was closely related to ferroptosis in Cd-induced TECs injury . Cd-induced ferroptosis and resultant TECs injury are significantly alleviated due to HO-1 inhibition, demonstrating the crucial role of HO-1 in Cd-triggered ferroptosis. Further studies showed that accumulation of lipid peroxides due to iron overload and mitochondrial ROS (mtROS) generation was responsible for HO-1-triggered ferroptosis in Cd-induced cytotoxicity. In conclusion, the current study demonstrates that excessively upregulating HO-1 promotes iron overload and mtROS overproduction to trigger ferroptosis in Cd-induced TECs injury, highlighting that targeting HO-1-mediated ferroptosis may provide new ideas for preventing Cd-induced nephrotoxicity .
研究领域:
毒理学
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细胞生物学
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肾脏生理学
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产品关联
DOI
PubMed
高影响因子
Theranostics
·
2025
·Vol. 15
·期 17
·9131
·
IF 13.3
Minghao Li,Qiwei Yang,Jie Gao,Xudong Liu,Jihua Shi,Wenzhi Guo,Yi Zhang,Qiwen Yu,Xinzhi Sun,Shuijun Zhang
Background : Acute liver injury (ALI), a highly perilous clinical condition triggered by diverse etiological factors, frequently progresses to acute liver failure with life-threatening consequences. However, due to the limited intervention time window for ALF, donor shortages, challenges in utilizing marginal grafts, surgical complexity and risks, and the high economic burden, developing novel therapeutic strategies targeting ALI-induced ALF has become imperative. Methods : Through transcriptome analysis, we determined that ferroptosis is a key driver in the pathogenesis of ALI. To combat hepatocyte ferroptosis, we designed a novel mitochondria-targeted nanotuner (CPTD) for regulating mitochondrial oxidative stress and iron homeostasis imbalance during ALI. This nanotuner features a cerium oxide (CeO₂) nanozyme core with a polydopamine (PDA) coating, functionalized with triphenylphosphonium (TPP) for mitochondrial targeting and deferoxamine (DFO) for iron chelation. In vitro and in vivo experiments evaluated CPTD's ability to target mitochondria and the labile iron pool (LIP). Results : The nanotuner demonstrates dual regulatory capacity by effectively accumulating in hepatic mitochondria to concurrently scavenge reactive oxygen species (ROS) and sequester labile iron ions, thereby rectifying mitochondrial oxidative stress and iron dyshomeostasis. Comprehensive evaluations across multiple ALI models, mainly including hepatic ischemia-reperfusion injury and acetaminophen-induced hepatotoxicity, revealed that CPTD robustly inhibits ferroptosis, mitigates oxidative damage, attenuates inflammatory responses, and preserves hepatic function. Conclusions : Our findings establish this dual-targeting nanotuner as a promising therapeutic strategy for ALI, providing novel insights into mitochondrial redox and iron homeostasis modulation.
研究领域:
纳米医学
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肝脏病学
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氧化还原生物学
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线粒体生物学
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药物纳米技术
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2021
·Vol. 8
·期 10
·2004680
·
IF 16.806
Jingyi Guo,Lifan Duan,Xueying He,Shengbiao Li,Yi Wu,Ge Xiang,Feixiang Bao,Liang Yang,Hongyan Shi,Mi Gao,Lingjun Zheng,Huili Hu,Xingguo Liu
Mitochondrial DNA depletion syndrome (MDS) is a group of severe inherited disorders caused by mutations in genes, such as deoxyribonucleoside kinase (DGUOK). A great majority of DGUOK mutant MDS patients develop iron overload progressing to severe liver failure. However, the pathological mechanisms connecting iron overload and hepatic damage remains uncovered. Here, two patients’ skin fibroblasts are reprogrammed to induced pluripotent stem cells (iPSCs) and then corrected by CRISPR/Cas9. Patient-specific iPSCs and corrected iPSCs-derived high purity hepatocyte organoids (iHep-Orgs) and hepatocyte-like cells (iHep) are generated as cellular models for studying hepatic pathology. DGUOK mutant iHep and iHep-Orgs, but not control and corrected one, are more sensitive to iron overload-induced ferroptosis, which can be rescued by N-Acetylcysteine (NAC). Mechanically, this ferroptosis is a process mediated by nuclear receptor co-activator 4 (NCOA4)-dependent degradation of ferritin in lysosome and cellular labile iron release. This study reveals the underlying pathological mechanisms and the viable therapeutic strategies of this syndrome, and is the first pure iHep-Orgs model in hereditary liver diseases.
研究领域:
干细胞生物学
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分子遗传学
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细胞病理学
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肝病学
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DOI
PubMed
高影响因子
Food & Function
·
2023
·Vol. 14
·期 2
·1087-1098
·
IF 6.1
Chengzhu Song,Dongning Li,Jie Zhang,Xiaoyan Zhao
Imatinib mesylate (IMA) belonging to the selective tyrosine kinase inhibitor family has been proven to induce cardiotoxic effects along with therapeutic strategies. Nrf2-dependent ferroptosis has been implicated in the cardiotoxicity induced by IMA. The present study was designed to investigate the protective effects of berberine hydrochloride (Ber) on cardiac injuries induced by IMA and to explore its potential mechanisms. In H9c2 cells, cell viability, the generation of reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and labile iron pool (LIP) levels were measured. In a mouse model of IMA-induced cardiomyopathy, serum biomarkers and cardiac tissues were examined. A western blot assay was performed to evaluate the expression of ferroptosis-related proteins in vitro and in vivo. Our results indicated that Ber increased cell viability and MMP and decreased cellular ROS and iron levels in comparison to the IMA group of H9c2 cells. In mice, Ber significantly improved cardiac status and attenuated the level of ferroptosis biomarkers including malonaldehyde (MDA) and iron content. Additionally, Ber downregulated the expression of transferrin receptor (TfR) and P53 and upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase-1 (NQO1), ferritin heavy chain-1 (FTH1), and glutathione peroxidase 4 (GPX4) in H9c2 cells and mice. The present data indicated that Ber has the potential to protect against IMA-induced cardiotoxicity, partly via inhibiting Nrf2-dependent ferroptosis.
研究领域:
药理学
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心脏病学
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毒理学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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