Ask about this productRelated genes to: AKR1C1 Blocking Peptide
- Gene:
- AKR1C1 NIH gene
- Name:
- aldo-keto reductase family 1 member C1
- Previous symbol:
- DDH1
- Synonyms:
- DDH, MBAB, DD1, HAKRC
- Chromosome:
- 10p15.1
- Locus Type:
- gene with protein product
- Date approved:
- 1994-09-14
- Date modifiied:
- 2016-10-05
Related products to: AKR1C1 Blocking Peptide
Related articles to: AKR1C1 Blocking Peptide
- Bisphenol A (BPA) is a widely used plastic monomer with well-established endocrine-disrupting properties and emerging evidence for metabolism-disrupting effects. Following regulatory restrictions, structurally modified alternatives, including halogenated derivatives, have been introduced, but information on their metabolic effects remains scarce. Hence, we analyzed proteomic and metabolomic responses in SGBS human adipocytes after exposure to BPA and five analogues (TBBPA, TCBPA, BPS, TBBPS, and TCBPS), including environmentally relevant concentrations of 10 nM. Intracellular target proteins were identified using thermal proteome profiling (TPP). All tested alternatives significantly increased intracellular triglyceride levels, indicating adipogenic potential. Proteomic and metabolomic analyses revealed alterations in lipid and energy metabolism and the central carbon cycle. TPP identified protein targets within steroid hormone pathways, fatty acid, central carbon, and amino acid metabolism, which were confirmed by nano differential scanning fluorimetry. Among these, AKR1C1 showed strong binding interactions with the tested bisphenols, resulting in reduced enzymatic activity. Pharmacological inhibition of AKR1C1 induced metabolic changes resembling those caused by BPS and its halogenated derivates. Overall, these findings identify AKR1C1 as a potential molecular target of halogenated bisphenols and demonstrate that these compounds disrupt adipocyte metabolism highlighting the importance of mechanistic data of chemical risk assessment. - Source: PubMed
Publication date: 2026/08/12
Kleißen JasminGoerdeler CorneliusAldehoff Alix SarahKarkossa IsabelDidio AnnaSchmidt JohannesKalkhof StefanLehmann JörgRolle-Kampczyk UlrikeGrimaldi MarinaBalaguer PatrickFaissner MaximilianFlamm ChristophWabitsch MartinHeiker John ThomasSchubert Kristinvon Bergen Martin - Lipedema is a chronic disorder of subcutaneous adipose tissue characterized by disproportionate fat accumulation, pain, and progressive functional impairment, predominantly affecting women. Research remains fragmented across vascular, hormonal, metabolic, and gynecologic perspectives. Recent contributions have advanced specific axes: an international Delphi consensus, a systematic review of hormonal hypotheses, a stromal-vulnerability narrative, and a focused review of adipose biology; but no prior framework has integrated these domains into a single architecture annotated by level of evidence and capable of generating stratified, falsifiable research hypotheses. Here, we propose a hypothesis-generating translational framework that conceptualizes lipedema as the predominant adipose expression of a hormone-sensitive stromal vulnerability. The framework adds a specific molecular convergence axis, ERα/ERβ signaling imbalance interacting with intracrine steroid metabolism (aromatase, 17β-HSDs, AKR1C1), and resolves the disorder into four interacting biological pathways: (i) hormonal transition sensitivity across the female life course; (ii) metabolic-behavioral amplification; (iii) gynecologic-endocrine comorbidity; and (iv) intrinsic stromal-adipose susceptibility. The framework predicts that lipedema and its cognate expressions in hormone-responsive tissues (including gynecologic disease, connective tissue laxity, microvascular dysfunction, neurosensory amplification, and neuropsychological burden) may share a common stromal-endocrine substrate while preserving phenotypic specificity through dominant-pathway combinations. Four features distinguish this framework from prior syntheses: (a) ERα/ERβ signaling imbalance is articulated as a candidate molecular convergence axis linking adipose, gynecologic, connective-tissue, microvascular, and neuro-immune manifestations; (b) intracrine steroid metabolism (aromatase, 17β-HSDs, AKR1C1) is incorporated as the mechanistic anchor of stromal hormone-responsiveness; (c) per-component evidence-level annotation is applied throughout (Level 1A/1B: direct evidence in lipedema; Level 2: observational association; Level 3: mechanistic extrapolation); and (d) stratified, falsifiable research hypotheses are derived from dominant-pathway phenotypes. Two domains, metabolic burden and steroid signaling, emerge as promising translational research domains. Important limitations apply. Direct mechanistic evidence in lipedema-specific tissues is limited; much of the supporting biology is extrapolated from adipose, gynecologic, and metabolic literature; and most clinical data derive from observational cohorts in referral centers. This article therefore proposes a hypothesis-generating translational framework, not a clinical guideline or therapeutic recommendation. - Source: PubMed
Publication date: 2026/07/22
Viana Diogo Pinto da CostaInvitti Adriana LuckowSchor Eduardo - Smoking is a well-established risk factor for esophageal squamous cell carcinoma (ESCC), yet its impact on the tumor microenvironment (TME) remains incompletely understood. Using single-cell RNA sequencing of ESCC samples, we identified distinct TME compositions between smokers and non-smokers. Smokers exhibited altered epithelial cell subpopulations and a T-cell compartment skewed towards exhaustion, with higher proportions of exhausted T cells and fewer helper subsets. Cell-cell communication analysis revealed smoking-associated perturbations in key signaling pathways. Chronic cigarette smoke extract exposure validated the upregulation of malignancy-related genes (e.g., AKR1C1-3, LDHA, NFE2L2) in esophageal cells. Functionally, nicotine, a key smoke constituent, directly impaired CD8⁺ T cell cytotoxicity against ESCC cells in a dose-dependent manner, correlating with reduced granzyme B secretion and increased expression of exhaustion markers (Tim-3, PD-1), without inducing direct tumor cell apoptosis. These results demonstrate that smoking reshapes the ESCC TME, promoting an immunosuppressive niche through induction of CD8⁺ T cell exhaustion, suggesting a potential mechanism for smoking-associated ESCC progression. - Source: PubMed
Publication date: 2026/07/28
Zhou YuetingMa YikaiCao KexinShi XiaolingWu KushengWang GengLiu Caixia - Secondary "keto" bile acids (BAs) are produced by the gut microbiome and contain one or more ketones on the steroid core. Plasma concentrations of keto BAs are limited by hepatic reductase activity, leading to hydroxylation of keto BAs. Although the aldo-keto reductase 1 (AKR1) family is implicated, it is not known which enzymes provide this function in the liver. We hypothesized that AKR1C1 and AKR1C4 metabolize 3-keto BAs. Six BAs with 3-keto groups were tested as potential substrates using purified, recombinant His-tagged AKR1C1-4, and kinetic parameters were determined. AKR1C1 and AKR1C4 were found to exhibit isoform-specific substrate specificity, which may be explained in part by the hydroxylation pattern at carbon 12 of the BA core. This may suggest distinct biological roles in mediating BA homeostasis in humans. Both enzymes produced only α-OH products, as determined by liquid chromatography-mass spectrometry. We further hypothesized that fatty acids would impair reductase activity. AKR1C4 was more susceptible to inhibition compared to AKR1C1, but unsaturated fatty acids, such as linoleic acid, were the most potent inhibitors for both. We observed a 2- to 10-fold difference in the IC of fatty acids for AKR1C4 depending on the tested substrate. Further mechanistic and structure-function studies aim to characterize the substrate-specific kinetic and inhibition patterns observed and to evaluate the translational impact of AKR activity on plasma BA concentrations and cellular signaling. SIGNIFICANCE STATEMENT: Keto bile acids are bioactive secondary metabolites that are reduced upon enterohepatic recycling to the liver. Here, the substrate specificity, kinetics, and inhibition potential of 2 aldo-keto reductase enzymes, AKR1C1 and AKR1C4, were evaluated. This study suggests that AKR1C1 and AKR1C4 exhibit disparate substrate specificity patterns, reductase activity, and susceptibility to inhibition by fatty acids, which may have broad implications in understanding changes in bile acid homeostasis in metabolic diseases. - Source: PubMed
Publication date: 2026/06/02
Green Keith DThomason Graham KCzuba Lindsay C - - Source: PubMed