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
- Vitamin C (VC) plays essential but incompletely defined roles in osteoclast (OC) development. We examined how exogenous VC and AKR1A-dependent endogenous VC regulate OC differentiation, cytoskeletal organization, resorptive activity, and apoptosis. - Source: PubMed
Publication date: 2026/05/13
Chiang Chen HaoHuang Cian-CiMa Yi-ShingWu Yu-TingKuo Chia-HsiaWei Yau-HueiChen Chuan-MuLiou Ying-Ming - Aldo-keto reductase family 1 member A1 (AKR1A1) is a nicotinamide adenine dinucleotide phosphate (NADPH)-dependent enzyme that catalyzes the reduction of aldehydes to alcohols. In this study, we investigated whether AKR1A1 acts as a context-dependent stress-associated factor whose role may differ depending on the degree, duration, and cellular context of injury in kidney allografts and explored its underlying molecular mechanisms. In human kidney transplant specimens, AKR1A1 expression was upregulated in renal tubular epithelial cells (RTECs) exhibiting tubular injury and oxidative stress, particularly during rejection accompanied by acute tubular injury. Although AKR1A1 expression showed an inverse correlation with pyruvate kinase muscle isoenzyme 2 (PKM2), this association was statistically non-significant. Notably, higher AKR1A1 expression was associated with increased oxidative stress yet correlated with a reduced risk of serum creatinine doubling in this cohort. In vitro, hypoxia/reoxygenation (H/R) reduced cell viability and induced AKR1A1 expression alongside the pro-apoptotic marker C/EBP homology protein (CHOP). Pharmacological inhibition of S-nitrosoglutathione reductase using N6022 functionally attenuated AKR1A1 activity without a direct effect on CHOP expression. Genetic modulation further confirmed the role of AKR1A1 in apoptosis, as AKR1A1 knockdown increased CHOP expression, whereas AKR1A1 overexpression attenuated it. Reciprocal activation between AKR1A1 and the silent information regulator 1 (SIRT1)/peroxisome-proliferator-activated receptor γ coactivator-1α (PGC-1α) pathway was observed both in vitro and in vivo. In addition, N6022 altered LC3B-associated autophagy markers, suggesting the activation of compensatory cytoprotective mechanisms under conditions of AKR1A1 deficiency. Together, these findings indicate that AKR1A1 serves as a marker of tubular stress and contributes to kidney allograft survival by modulating CHOP-mediated apoptosis and the SIRT1/PGC-1α axis. Inhibitory S-nitrosylation and activation of SIRT1/PGC-1α provide compensatory protection against oxidative stress and apoptosis. Targeting these pathways may represent a promising therapeutic strategy to improve kidney allograft outcomes. - Source: PubMed
Publication date: 2026/05/07
Tsai Yong-LiangLiou Ying-MingChen Chuan-MuWu Chia-LinHsu Chiann-YiWeng Shuo-Chun - 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