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Signal transduction and exercise
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Brendan Egan, Adam P. Sharples
Investigating changes in mRNA abundance by transcriptomics (i.e. gene expression profiling using expression microarrays or RNA-seq) has provided enormous insight into the effect of acute exercise on the transcriptional profile of skeletal muscle, as well as effects on skeletal muscle induced by inactivity or more chronic exercise training. Recently, data collected from human studies of aerobic and resistance exercise, including acute exercise sessions and chronic exercise training, were integrated using meta-analysis methods to create an online open access database known as MetaMEx (www.metamex.eu), alongside an interface to readily interrogate the database (50). This database at the time of writing contained 66 transcriptomic datasets from human skeletal muscle, including 13 studies of acute aerobic exercise, and 8 studies of acute resistance exercise. In one interrogation of the database using gene ontology and pathway analyses on the expression profiles, a transcription factor NR4A3 (nuclear receptor 4A3; also known as NOR-1) was identified as one of the most exercise- and inactivity-responsive genes, with the expression of this transcription factor being induced by both aerobic and resistance exercises (50). Notably in the spirit of the discovery that is a goal of unbiased omics approaches, NR4A3 had not been previously identified by authors of the individual published datasets, despite this transcription factor having regulatory roles in skeletal muscle consistent with producing an endurance phenotype (103). With these findings in mind, in an independent study, it was subsequently demonstrated that marked changes in NR4A3 mRNA abundance 3 hours after change-of-direction repeated sprint running, with these changes coinciding with hypomethylation of the NR4A family of genes (61).
Pterostilbene pre-treatment reduces LPS-induced acute lung injury through activating NR4A1
Published in Pharmaceutical Biology, 2022
Ying Li, Shu-Min Wang, Xing Li, Chang-Jun Lv, Ling-Yun Peng, Xiao-Feng Yu, Ying-Jian Song, Cong-Jie Wang
The nuclear receptor subfamily 4 group A member (NR4A) family, which consists of three members, NR4A1, NR4A2, and NR4A3, is associated with various cellular processes, including cellular proliferation, apoptosis, and energy utilization (Herring et al. 2019). Herring et al. (2019) also reported that NR4A1 and NR4A2 inhibited cell proliferation in the liver, while NR4A3 had the opposite effect in controlling the proliferation of hepatocytes and hepatic stellate cells. Banno et al. (2019) reported that NR4A1 played a pivotal role in regulating inflammatory responses through its function in the NF-κB pathway. In particular, NR4A1 could upregulate the expression of p65 downstream genes by weakening the binding ability of p65 and DNA. NR4A1 directly promoted the expression of IκB (Huang et al. 2016) and regulated the activity of the NF-κB pathway through non-protein-protein interactions (Kalogeris et al. 2012). When investigating other inflammation-related diseases, NR4A1 was demonstrated to inhibit the inflammatory response and delay disease progression (Nakazato et al. 2018). Therefore, we put forward a hypothesis that NR4A1 plays an important role in the LPS induced ALI, and the pre-protective effects of PTE might be associated with the NR4A1 expression.
Yiqi Huoxue Tongluo recipe regulates NR4A1 to improve renal mitochondrial function in unilateral ureteral obstruction (UUO) rats
Published in Pharmaceutical Biology, 2022
Zhen He, Mengjuan Zhang, Hepeng Xu, Wenping Zhou, Chang Xu, Zheng Wang, Ming He, Xiangting Wang
The nuclear receptor superfamily includes at least 48 transcription factors that regulate a variety of cellular and metabolic functions in different biological processes (Chawla et al. 2001). The NR4A family is an orphan nuclear receptor and consists of three members: NR4A1 (NUR77), NR4A2 (NURR 1), and NR4A3 (NOR-1) (Nuclear Receptors Nomenclature Committee 1999). For these receptors, the endogenous ligands are not recognized (Kliewer et al. 1999). Therefore, the regulatory activity of the NR4A1 is ligand-independent, and the function of NR4A1 is receptor-dependent for expression and post-translational modifications (Wang et al. 2003). In Nr4a1–/– mice, the severity of tubular atrophy, tubular casts, and interstitial fibrosis were significantly increased, accompanied by massive infiltration of immune cells, mainly macrophages, T cells, and B cells (Zhang et al. 2018). In our study, we found that the expression of NR4A1 in kidney of UUO rats was increased and inhibited by YHTR and eplerenone (Figure 2).
Radiotherapy in combination with hyperthermia suppresses lung cancer progression via increased NR4A3 and KLF11 expression
Published in International Journal of Radiation Biology, 2019
Beomseok Son, Jaewan Jeon, Sungmin Lee, Hyunwoo Kim, Hyunkoo Kang, HyeSook Youn, Sunmi Jo, BuHyun Youn
Nuclear receptor subfamily 4, group A, member 3 (NR4A3) also called neuron-derived orphan receptor 1, is a nuclear receptor family member of intracellular transcription factors. It is expressed in various tissues and can be induced by fatty acids, growth factors, inflammatory cytokines, and neurotransmitters (Maxwell and Muscat 2006). NR4A3 is reported to regulate cell proliferation, survival, and apoptosis. A study has demonstrated that NR4A3 suppressed the hyper-proliferation of hematopoietic stem cell by directly binding to Cebpa enhancer and activating its transcription (Freire and Conneely 2018). Chio and colleagues showed that NR4A3 mediates hypoxia-induced alterations in the survival signals and apoptosis of Neuro-2a cells (Chio et al. 2016). Moreover, NR4A3 is known to possess tumor-suppressive properties in acute myeloid leukemia, lymphoma, and gastric cancer (Deutsch et al. 2015; Wenzl et al. 2015; Yeh et al. 2016). However, the role of NR4A3 in promoting lung cancer cell death during therapy has not been elucidated.