Ask about this productRelated genes to: Arnt antibody
- Gene:
- ARNT NIH gene
- Name:
- aryl hydrocarbon receptor nuclear translocator
- Previous symbol:
- -
- Synonyms:
- HIF-1beta, bHLHe2
- Chromosome:
- 1q21.3
- Locus Type:
- gene with protein product
- Date approved:
- 1990-01-22
- Date modifiied:
- 2016-10-05
Related products to: Arnt antibody
Related articles to: Arnt antibody
- Obesity-related cardiomyopathy (OCM) is characterized by pathological cardiac remodeling and progressive functional decline, often accompanied by mitochondrial dysfunction, particularly aberrant mitophagy. The role of the core circadian gene brain and muscle ARNT-like protein 1 ( ) in OCM remains unclear. In this study, we employed a high-fat diet (HFD)-induced OCM mouse model, a cardiomyocyte-specific knockout ( ) model, and a palmitic acid (PA)-induced H9c2 cardiomyocyte injury model to investigate the function of . , BMAL1 expression was reduced in hearts of HFD mice; HFD- mice exhibited exacerbated myocardial hypertrophy, fibrosis, functional impairment, and apoptosis, accompanied by increased expression of the mitophagy-related proteins PINK1, Parkin, and LC3-II. , PA exposure decreased BMAL1 expression, disrupted mitochondrial membrane potential, increased reactive oxygen species generation, and induced excessive mitophagy; these effects were aggravated by silencing and attenuated by overexpression, which also improved cell viability. Collectively, these findings indicate that plays a protective role in OCM, and its downregulation may be a key contributor to obesity-induced cardiac remodeling and dysfunction. Mechanistically, BMAL1 downregulation was accompanied by activation of the PINK1/Parkin signaling and enhanced mitophagy under lipid stress. By restraining excessive mitophagy and preserving mitochondrial function and metabolic homeostasis, and its associated pathways may represent promising therapeutic targets for OCM. - Source: PubMed
Publication date: 2026/05/25
Liu TianziFan XiaoxuanZhang NannanWang YaoQian ZhiyongHou XiaofengZhang HanwenZou Jiangang - The circadian clock regulates diverse physiological and immune processes through transcriptional feedback loops, with Bmal1 (Brain and Muscle Arnt-like protein 1) as a core component. Although well studied in mammals, its immunological role in teleosts remains unclear. In this study, we examined the effects of Bmal1 deficiency on the fish immune system, by generating a Bmal1 knockout (Bmal1 KO) Japanese medaka (Oryzias latipes) using CRISPR-Cas9, introducing a 16-bp insertion in exon 4, which disrupted the bHLH and PAS domains. Unlike wild-type (WT) fish, Bmal1 KO individuals remained active during ZT21, suggesting altered time-of-day-dependent activity patterns. Exploratory RNA-seq analysis of the head kidneys under phosphate buffered saline and lipopolysaccharide stimulation revealed broad transcriptional changes, with 481 and 767 genes showing altered expression patterns in Bmal1 KO fish under control and LPS-stimulated conditions, respectively. Gene Ontology analysis suggested that among the top-ranked functional groups in Bmal1 KO fish, immune-related categories were less prominent whereas reproductive and vitellogenin-associated processes were more prominent, suggesting alteration of functional profiles rather than direct suppression of immune pathways. Infection assays at ZT2 demonstrated induction of ifng, tnfa, tlr1, tlr5m, tlr9, and tlr21 after bacterial challenge in WT medaka. In contrast, Bmal1 KO fish exhibited an altered response pattern -elevated expression in controls but reduced inducibility after infection. Bmal1 may thus contribute to time-of-day-dependent coordination of circadian and immune signaling, including potential involvement of NF-κB-related pathways. Loss of Bmal1 alters immune gene expression patterns and pathogen responsiveness in a time-of-day-dependent manner. Overall, Bmal1 deficiency was associated with altered clock-gene expression patterns and immune responses at specific Zeitgeber times. Therefore, Bmal1 may contribute to the time-of-day-dependent regulation of innate immune gene expression in medaka; however, circadian rhythmicity of immune responses remains to be directly demonstrated. - Source: PubMed
Publication date: 2026/05/19
Hata TakahikoTsuda KazutadaHirayoshi MiyuMiyanishi HiroshiHikima Jun-IchiKono Tomoya - Cisplatin-induced acute kidney injury (AKI) is characterized by profound oxidative stress and mitochondrial dysfunction in proximal tubular cells. However, the upstream mechanisms governing this redox imbalance remain incompletely defined. Here, we identify mitochondrial calcium uptake 1 (MICU1) as a critical regulator of tubular redox homeostasis. Using integrated multi-omics approaches, we found that MICU1 is markedly downregulated in injured proximal tubular subpopulations across various kidney diseases. Mechanistically, MICU1 deficiency disrupts mitochondrial calcium homeostasis, resulting in calcium overload and excessive mitochondrial reactive oxygen species (mtROS) generation. These changes trigger intrinsic apoptotic pathways, whereas MICU1 restoration alleviates such damage. Furthermore, we demonstrate that the ARNT/HIF-1α axis transcriptionally regulates MICU1. Under cisplatin stress, this axis is suppressed, thereby promoting mitochondrial dysfunction. Crucially, we found that MICU1-mediated mtROS control contributes to the preservation of epidermal growth factor receptor (EGFR) signaling, whereas excessive mtROS accumulation is associated with EGFR signaling impairment. Importantly, pharmacological targeting of mitochondrial calcium uptake using the small-molecule modulator MCU-i4 attenuates calcium overload, suppresses mtROS accumulation, and mitigates renal injury in vitro and in vivo. Collectively, our findings support a transcriptional-mitochondrial axis linking calcium dysregulation to oxidative stress and identify MICU1 as a potential therapeutic target for redox-driven kidney injury. - Source: PubMed
Publication date: 2026/05/20
Dong BoqingBi HuanjingLi YangWang ChongfengWang JingwenChen ZuhanWang YingWang YihanWang JialeLu CuinanDing Xiaoming - Long QT syndrome (LQTS) is an inherited life-threatening cardiac disorder characterized by delayed ventricular repolarization and increased risk of malignant arrhythmias. Among its subtypes, long QT syndrome type 2 (LQT2) is primarily caused by pathogenic variants in KCNH2, which encodes the human ether-à-go-go-related gene (hERG) potassium channel responsible for the rapid delayed rectifier current (I). However, the substantial functional heterogeneity among KCNH2 variants poses a major challenge for clinical interpretation and precision intervention. In this study, we sought to functionally characterize KCNH2 p.F68C variant (c.203T > G) identified in a Chinese LQT2 patient and to evaluate the feasibility of RNA interference-based modulation of its functional impact on the hERG channel. Using biochemical and electrophysiological analyses in HEK293T cells, we show that variant p.F68C causes a severe trafficking defect and exerts a dominant-negative effect on wild-type hERG channels, leading to markedly reduced rapid delayed rectifier potassium current (I). In contrast to several previously reported Per-Arnt-Sim (PAS) domain variants, the trafficking defect of p.F68C was resistant to reduced culture temperature, chemical chaperones, and pharmacological chaperones. Notably, allele-specific RNA interference selectively suppressed mutant hERG expression, alleviated dominant-negative interference, and partially restored hERG current density without detectable cytotoxicity. Together, these findings establish p.F68C as a loss-of-function KCNH2 variant and highlight allele-specific RNA interference as a variant-directed strategy that may serve as an alternative to suppression-replacement approaches, providing a basis for functional interpretation and precision therapeutic exploration of individual KCNH2 variants. - Source: PubMed
Publication date: 2026/05/19
Zhao MiaoHan MengLi WenjuanWang ZhijieChen LiZeng HanyuZhou ZiqiHu DongpingCheng YuWang QingKe Tie - The oxygen environment within malignant solid tumors is highly heterogeneous, with anoxic regions arising where oxygen supply is insufficient. It is known that oxygen depletion is one of the most influential factors that confer radioresistance on cancer cells. The resistance under low oxygen conditions has been attributed to both hypoxia-inducible genes-dependent biological mechanisms and genes-independent chemical mechanisms resulting from reduced production of radiation-induced reactive oxygen species. However, the relative contributions of these mechanisms have remained unclear. Moreover, although hypoxia-inducible factors (HIFs) are suggested to play key roles in hypoxia-inducible genes-dependent biological mechanisms, it has remained uncertain whether and how HIFs affect the intrinsic radioresistance of cancer cells. Here, we developed an approach to separately analyze the mechanisms behind radioresistance under anoxia as either hypoxia-inducible genes-dependent biological or genes-independent chemical mechanisms and found that the relative contributions in HeLa cells were 64.4 ± 9.06% and 35.6 ± 4.32%, respectively. In addition, HIF-1β alone, rather than heterodimeric HIF-1, HIF-2, or HIF-1β/AhR, was found to enhance the baseline radioresistance of cancer cells, irrespective of oxygen availability. RNA-sequencing-based screening further identified NRF2 and TXNRD1 as downstream effectors of HIF-1β underlying this baseline radioresistance. Taken together, these findings delineate the quantitative contributions of distinct mechanisms and identify HIF-1β-mediated signaling as a key determinant of baseline radioresistance, providing a framework for understanding how oxygen availability shapes tumor radioresistance and, in turn, a basis for developing strategies to overcome it. - Source: PubMed
Publication date: 2026/05/15
Takeuchi SatoshiKobayashi MinoruLee Peter Wai TikTakahashi ItsukiYoshihara ToshitadaHarada Hiroshi