Ask about this productRelated genes to: AKR1A1 antibody
- Gene:
- AKR1A1 NIH gene
- Name:
- aldo-keto reductase family 1 member A1
- Previous symbol:
- -
- Synonyms:
- ALR, DD3
- Chromosome:
- 1p34.1
- Locus Type:
- gene with protein product
- Date approved:
- 1998-09-29
- Date modifiied:
- 2016-10-05
Related products to: AKR1A1 antibody
Related articles to: AKR1A1 antibody
- Nitric oxide (NO•) is an important regulatory molecule in many biological processes, including immune response. During response to classical activation stimuli lipopolysaccharide (LPS) and interferon-γ (IFNγ), macrophages generate NO• via inducible nitric oxide synthase (iNOS). To comprehensively characterize the effects of NO•, we applied a multi-omic strategy integrating proteomics and transcriptomics to profile murine macrophages across conditions with or without LPS/IFNγ-activation, with or without iNOS expression or exogenous NO• donor treatment. The results showed NO• has broad, yet selected and controlled, regulatory effects, playing a key role in coordinating the systematic remodeling during macrophage classical activation. Among the proteins that are most suppressed in a NO•-dependent manner, electron transport chain (ETC) is the most enriched. NO• drives complex-specific remodeling of ETC, causing selected downregulation of complex I, II, and IV, through a different combination of transcriptional and post-transcriptional mechanisms for each complex. Among the most consistently NO•-dependent upregulated proteins are many enzymes involved in redox defense, and AKR1A1 was identified as a top hit. We found Akr1a1 induction requires both NO• and LPS/IFNγ stimulation. The S-nitroso-CoA reductase activity of AKR1A1 mitigates NO•-driven inhibition of pyruvate dehydrogenase complex by limiting the inhibitory modifications targeting its lipoyl cofactor. Knocking out Akr1a1 causes accelerated remodeling of TCA cycle, dysregulated immunoregulatory metabolite level, and altered functional gene expression and cytokine production at later stage of immune response. Thus, the NO•-dependent upregulation of AKR1A1 forms a negative regulatory loop to fine-tune NO•-mediated metabolic and functional remodeling during immune response. Together, this work provided a systems-level map of NO•-dependent regulation, revealed the crosstalk between NO• and immune signaling, and demonstrated mechanisms providing adaptation and precise control of NO•'s effects. - Source: PubMed
Publication date: 2026/04/22
Arp Nicholas LUrquiza Uzziah SMorgenstern MarcelSchrope Jonathan HVotava James AJohn Steven VStevens Jack JDeng FeliciaHuttenlocher AnnaCoon Joshua JFan Jing - Ovarian cancer (OC), characterized by a high mortality rate and limited treatment options, underscores the urgent need to identify novel therapeutic targets to advance individualized precision therapy. Exploring the potential of antidiabetic drug target genes as therapeutic candidates may expand the treatment repertoire of diverse OC subtypes. - Source: PubMed
Publication date: 2026/03/10
Tang EnyuZeng JiaShi XinlongWang YaniSun YangchunWu Lingying - Advanced glycation end products (AGEs) are a heterogeneous group of glycation-derived compounds that accumulate under metabolic stress and contribute to age-related and chronic diseases. Pentosidine (PEN), a well-characterized fluorescent AGE, increases during aging under certain pathological conditions. In particular, increased PEN levels have been observed in a subset of patients with schizophrenia and are associated with more severe clinical outcomes. Glucuronic acid (GlcA) has previously been identified as a metabolic precursor of PEN, and impaired GlcA metabolism due to reduced aldo-keto reductase family 1 member A1 (AKR1A1) activity may underlie PEN accumulation. In the present study, to investigate the neurobiological impact of endogenous PEN accumulation, we examined neurobehavioral consequences using Akr1a knockout (KO) mice, which exhibit impaired GlcA metabolism. These mice exhibited significantly elevated PEN levels in both the plasma and prefrontal cortex (Pfc), a brain region critically involved in higher-order cognitive and behavioral regulation, accompanied by increased aggression and hyperactivity-behavioral domains relevant to patients with schizophrenia. Notably, aggression measures were positively correlated with PEN concentrations, whereas PEN levels were associated with novelty-driven exploratory locomotion but not with sustained baseline locomotor activity. Transcriptomic analysis of Pfc revealed altered expression of genes involved in guanylate cyclase signaling, cytoskeletal organization, and the immune response. Cyclic guanosine monophosphate (cGMP) levels were significantly reduced, suggesting impaired downstream signaling. Together, these findings demonstrate that GlcA-driven PEN accumulation induces molecular and behavioral alterations in the brain and provides a dimensional mouse model linking glycation-related metabolic stress to aggression and hyperactivity relevant to schizophrenia. - Source: PubMed
Publication date: 2026/02/21
Iino KyokaToriumi KazuyaMiyashita MitsuhiroSuzuki KazuhiroTabata KoichiMiyata SatoshiTakahashi MotokoFujii JunichiItokawa MasanariArai Makoto - KFP-1, a kefir-fermented peptide, promotes osteoblast differentiation and bone formation while inhibiting osteoclast differentiation and bone resorption. We also confirmed the bioaccessibility of KFP-1 in bone tissue and its overall benefits for bone health. Kefir is a dairy beverage rich in bioactive peptides with diverse health benefits. We identified a kefir-fermented peptide, KFP-1 (TEVPAINTIASAEPTVH), which enhances intestinal calcium absorption and may modulate bone remodeling. This study investigated the effects of KFP-1 on osteoblast and osteoclast gene expression and differentiation in BMMSCs, MC3T3-E1, BMMs, and Raw264.7 cells. Using iodine-125 labeling, we tracked KFP-1 distribution in mice following oral and intravenous administration, and evaluated its osteoprotective effects in AKR1A1 knockout (AKR1A1-KO) osteoporotic mice. KFP-1 upregulated osteogenic markers (ALP, Col1a1, OCN, OPG, RUNX2, OSX, BMP-2, β-catenin) and promoted osteoblast differentiation and mineralization, while downregulating osteoclastic markers (CTK, CTR, DC-STAMP, TRAP, c-Fos, c-Src, NFATc1) and inhibiting osteoclast differentiation and resorption via the inhibition of NFATc1, c-Fos, and c-Jun nuclear translocation and attenuation of RANKL-induced p38 MAPK, JNK, ERK, and NF-κB signaling. Biodistribution analysis showed KFP-1 reached femur and tibia at approximately 0.4% (oral) and 1% (intravenous) of the administered dose. In AKR1A1-KO mice, oral KFP-1 prevented bone loss, with additional calcium supplementation further improving cortical bone mechanical properties. These findings highlight KFP-1's dual action in promoting bone formation and inhibiting bone resorption, supporting its potential as a therapeutic adjuvant or functional food ingredient for osteoporosis prevention and bone health. - Source: PubMed
Publication date: 2026/02/17
Tung Min-CheChang Gary Ro-LinTu Min-YuFan Hueng-ChuenYen Chih-ChingCidem AbdulkadirChen I-ChienChen Chuan-Mu - - Source: PubMed
Publication date: 2026/01/16
Cui JintaoXu BinZhang PenghuiHan SongfuGuo ChaoyanngWei Limin