Ask about this productRelated genes to: KEAP1 Blocking Peptide
- Gene:
- KEAP1 NIH gene
- Name:
- kelch like ECH associated protein 1
- Previous symbol:
- -
- Synonyms:
- KIAA0132, MGC10630, MGC1114, MGC20887, MGC4407, MGC9454, INrf2, KLHL19
- Chromosome:
- 19p13.2
- Locus Type:
- gene with protein product
- Date approved:
- 2003-09-30
- Date modifiied:
- 2015-11-23
Related products to: KEAP1 Blocking Peptide
Related articles to: KEAP1 Blocking Peptide
- Low-fishmeal diets often impair feed utilization and disturb physiological homeostasis in carnivorous fish, and supplementation with umami-related amino acids may help counteract these effects. This study evaluated the effects of dietary alanine or glycine supplementation in largemouth bass (Micropterus salmoides) fed low-fishmeal diets. Seven isonitrogenous and isolipidic diets were formulated, including a low-fishmeal control diet and six diets supplemented with alanine or glycine at 0.5%, 1.0%, or 2.0%. Juvenile fish (initial body weight 4.60 ± 0.01 g) were fed these diets for 8 weeks. Compared with the control, alanine or glycine supplementation increased weight gain and specific growth rate, reduced feed conversion ratio, and decreased feeding rate. The most consistent improvements were observed with 1.0% alanine and 0.5% glycine. Moderate supplementation also improved intestinal villus morphology and was associated with more favorable hepatic biochemical and redox profiles. In the liver, alanine or glycine elevated superoxide dismutase and catalase activities and reduced malondialdehyde content, indicating improved redox status. These biochemical changes were accompanied by transcriptional responses consistent with enhanced antioxidant regulation and attenuated inflammatory signaling, including increased nuclear factor erythroid 2-related factor 2 (nrf2) and catalase (cat), decreased Kelch-like ECH-associated protein 1 (keap1) in the most responsive groups, downregulated nuclear factor kappa B (nf-κb) and interleukin-1 beta (il-1β), and upregulated interleukin-10 (il-10). Although appetite-related genes also responded to supplementation, these changes were not associated with increased feeding rate. Collectively, dietary alanine or glycine improved feed utilization and growth performance, together with coordinated gut-liver physiological responses, without a corresponding increase in feeding rate. - Source: PubMed
Publication date: 2026/05/18
Jiang XiaoChen XiaochuanXu DimeiWang QiulingLu KeWu JiaqiZeng MingWu XinruiLiang Xufang - Methotrexate (MTX) is a widely used immunosuppressive and chemotherapeutic agent known to induce cardiotoxicity through mechanisms involving oxidative stress, inflammation, and apoptosis. The present study investigated the cardioprotective effects of Ajwa date methanolic extract (AJDAE) against MTX-induced cardiac injury in rats, with emphasis on biochemical alterations, histopathological changes, immunohistochemical markers, and exploratory molecular docking. Forty male rats were randomly divided into four groups: control, AJDAE alone, MTX alone, and AJDAE pretreated with MTX. Phytochemical profiling of AJDAE using liquid chromatography-mass spectrometry (LC-MS) in both positive- and negative-ion modes revealed a complex composition rich in phenolic acids, flavonoids, vitamins, and minerals, as shown by total ion chromatograms (TICs) and base peak chromatograms (BPCs). MTX administration significantly increased cardiac injury biomarkers, pro-inflammatory cytokines, oxidative stress markers, and the apoptotic marker caspase-3, together with marked histopathological alterations, including myocardial necrosis. In addition, antioxidant defense parameters, including reduced glutathione (GSH), superoxide dismutase (SOD), and paraoxonase 1 (PON1), were significantly decreased. Pretreatment with AJDAE markedly ameliorated these changes by improving antioxidant status, reducing inflammatory and apoptotic markers, and preserving myocardial architecture. AJDAE also restored nuclear factor erythroid 2-related factor 2 (Nrf2) immunoreactivity, suggesting improved cellular antioxidant defense and tissue protection. Molecular docking provided complementary exploratory evidence of favorable predicted interactions between selected AJDAE bioactive compounds and proteins related to apoptosis and oxidative stress, including caspase-3 and the Keap1 Kelch domain as an Nrf2-regulatory target. In conclusion, these findings suggest that AJDAE exerts cardioprotective effects against MTX-induced cardiac injury through attenuation of oxidative stress, inflammation, and apoptosis. The restoration of Nrf2 immunoreactivity, together with improved antioxidant markers, suggests possible involvement of Nrf2-related antioxidant defense; however, direct activation of the canonical Nrf2/ARE pathway was not confirmed and requires further validation using downstream molecular targets. - Source: PubMed
Publication date: 2026/05/13
Mahmoud Hany SalahAbdelrazek Heba M AEl-Hak Heba Nageh GadEl-Beltagy Marwa AKhalil Waleed FEltamnany DaliaBasha Walaa AaAbdelnaeim Noha S - Does peritoneal iron overload drive fibrosis in endometriosis through Nrf2 pathway dysfunction and the resulting ferroptosis, and can electroacupuncture intervene in this process? - Source: PubMed
Publication date: 2026/02/14
Zan YanZhuang YuZhu QianHuang XiaoquanLi JunweiXia LiangjunXia Youbing - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline, memory loss, and behavioral changes, with no effective treatments currently available. Oxidative stress has been shown to be associated with AD, but the causal relationship of AD by oxidative stress remains unestablished. Activation of the Nrf2 pathway is a powerful way to counteract oxidative stress. There are lines of evidence that the pathological features, including Aβ deposition, Tau phosphorylation, neuroinflammation, and mitochondrial dysfunction, could be ameliorated by different antioxidant measures. A group of Nrf2 pathway activators, functioning as Michael acceptors, can covalently modify the Keap1 protein. Such a reaction triggers a conformational change of Keap1, facilitating the release of functional Nrf2 and its subsequent translocation into the nucleus. As a result, a cascade of antioxidant related proteins is expressed. Many plant-derived compounds with Nrf2 pathway activation properties were shown to improve the AD symptom in animal models. This review summarizes the phytochemicals and FDA-approved drugs with diverse structure, including isothiocyanates, polyphenols, phenylpropanoids, flavonoids, terpenes, and alkaloids, but all with Nrf2 pathway activation function and effects on the ameliorating effects on AD symptoms. Three of FDA-approved drugs, being Nrf2 activators, are for the disorders in nervous system. Therefore, Nrf2 could be a promising target for future drug development based on rational design or on the screening from the phytochemicals. - Source: PubMed
Yuan LieAsghar Muhammad ArifZhang YazhenYang YuanyuanZhang XiaoZhao Qinjian - Septic cardiomyopathy (SCM) is a severe complication of sepsis. The therapeutic potential of Ginsenoside Rh4 (Rh4) in SCM remains unclear. This study aimed to investigate the effects and mechanisms of Rh4 on SCM using both in vivo and in vitro approaches. In the in vivo experiments, Rh4 significantly reduced the mortality rate in SCM mice, improved ejection fraction and diastolic function, and protected myocardial cell mitochondria, thereby alleviating myocardial cell injury. Transcriptomic sequencing, ELISA, and PCR results suggested that Rh4 reduced inflammatory cytokines in myocardial tissues, likely through the inhibition of the NF-κB signaling pathway. This effect was associated with a reduction in pro-inflammatory M1 macrophages and an increase in the proportion of reparative M2 macrophages. Additionally, Rh4 alleviated myocardial cell apoptosis and attenuated myocardial fibrosis at later stages. In vitro, we found that Rh4 reduced LPS-induced macrophage polarization and promoted the polarization of macrophages into anti-inflammatory M2 macrophages. Moreover, flow cytometry analysis revealed that Rh4 decreased reactive oxygen species (ROS) production in HL-1 cardiomyocytes, with the mechanism linked to the activation of the Keap1/Nrf2/HO-1 signaling pathway. Finally, Rh4 treatment significantly inhibited the pro-apoptotic effects of LPS on HL-1 cells. In conclusion, Rh4 improves heart function by reducing macrophage polarization and ROS generation, protecting myocardial cell mitochondria, and reducing myocardial cell apoptosis. - Source: PubMed
Publication date: 2026/05/18
Huang BingxinTang YueJiang XinpengShen HongtaoYang YidiJing LingYang HangLing YunpengSong Mowei