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Jing Wu, Wei-Wei Tao, Dan-Yang Chong, Shan-Shan Lai, Chuang Wang, Qi Liu, Tong-Yu Zhang, Bin Xue, Chao-Jun Li
Postprandial insulin desensitization plays a critical role in maintaining whole-body glucose homeostasis by avoiding the excessive absorption of blood glucose; however, the detailed mechanisms that underlie how the major player, skeletal muscle, desensitizes insulin action remain to be elucidated. Herein, we report that early growth response gene-1 ( Egr-1) is activated by insulin in skeletal muscle and provides feedback inhibition that regulates insulin sensitivity after a meal. The inhibition of the transcriptional activity of Egr-1 enhanced the phosphorylation of the insulin receptor (InsR) and Akt, thus increasing glucose uptake in L6 myotubes after insulin stimulation, whereas overexpression of Egr-1 decreased insulin sensitivity...
March 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Ae-Rang Hwang, Ju-Ock Nam, Young Jin Kang
Connective tissue growth factor (CTGF) is a novel fibrotic mediator, which is considered to mediate fibrosis through extracellular matrix (ECM) synthesis in diabetic cardiovascular complications. Statins have significant immunomodulatory effects and reduce vascular injury. We therefore examined whether fluvastatin has anti-fibrotic effects in vascular smooth muscle cells (VSMCs) and elucidated its putative transduction signals. We show that advanced glycation end products (AGEs) stimulated CTGF mRNA and protein expression in a time-dependent manner...
March 2018: Korean Journal of Physiology & Pharmacology
Ricardo González-Ramírez, Elizabeth Martínez-Hernández, Alejandro Sandoval, Kimberly Gómez-Mora, Ricardo Felix
It is well known that the CaV α2 δ auxiliary subunit regulates the density of high voltage-activated Ca2+ channels in the plasma membrane and that alterations in their functional expression might have implications in the pathophysiology of diverse human diseases such as neuropathic pain. However, little is known concerning the transcriptional regulation of this protein. We previously characterized the promoter of CaV α2 δ, and here we report its regulation by the transcription factor Egr-1. Using the neuroblastoma N1E-115 cells, we found that Egr-1 interacts specifically with its binding site in the promoter, affecting the transcriptional regulation of CaV α2 δ...
March 5, 2018: Neuroscience Letters
Takayuki Uchida, Yoshihiro Sakashita, Kanako Kitahata, Yui Yamashita, Chisato Tomida, Yuki Kimori, Akio Komatsu, Katsuya Hirasaka, Ayako Ohno, Reiko Nakao, Atsushi Higashitani, Akira Higashibata, Noriaki Ishioka, Toru Shimazu, Takeshi Kobayashi, Yuushi Okumura, Inho Choi, Motoko Oarada, Edward M Mills, Shigetada Teshima-Kondo, Shin'ichi Takeda, Eiji Tanaka, Keiji Tanaka, Masahiro Sokabe, Takeshi Nikawa
Unloading-mediated muscle atrophy is associated with increased reactive oxygen species (ROS) production. We previously demonstrated that elevated ubiquitin ligase casitas B-lineage lymphoma-b (Cbl-b) resulted in the loss of muscle volume [Nakao R. et al. Mol Cell Biol, 29: 4798-4811, 2009]. However, the pathological role of ROS production associated with unloading-mediated muscle atrophy still remains unknown. Here, we showed the ROS-mediated signal transduction caused by microgravity or its simulation contributes to Cbl-b expression...
March 7, 2018: American Journal of Physiology. Cell Physiology
Amal A Halawa, Joanne C Damborsky, G Simona Slaton, Ursula H Winzer-Serhan
Maternal smoking has negative long-term consequences on affective behaviors, and in rodents, chronic neonatal nicotine exposure (CNN) results in increased anxiety. In rat pups, acute nicotine stimulation activates brain regions associated with stress and anxiety, but chronic nicotine exposure could desensitize of nicotinic acetylcholine receptors, the molecular target of nicotine. Here, we determined whether CNN affected neuronal activation by an acute nicotine challenge. Using in situ hybridization, we analyzed mRNA expression of the immediate-early genes (IEGs) c-Fos, Arc, Egr-1 and Npas4, which are markers for neuronal activation and implicated in synaptic plasticity...
February 26, 2018: Brain Research
Eoin P Brennan, Muthukumar Mohan, Aaron McClelland, Christos Tikellis, Mark Ziemann, Antony Kaspi, Stephen P Gray, Raelene Pickering, Sih Min Tan, Syed Tasadaque Ali-Shah, Patrick J Guiry, Assam El-Osta, Karin Jandeleit-Dahm, Mark E Cooper, Catherine Godson, Phillip Kantharidis
Background The failure of spontaneous resolution underlies chronic inflammatory conditions, including microvascular complications of diabetes such as diabetic kidney disease. The identification of endogenously generated molecules that promote the physiologic resolution of inflammation suggests that these bioactions may have therapeutic potential in the context of chronic inflammation. Lipoxins (LXs) are lipid mediators that promote the resolution of inflammation. Methods We investigated the potential of LXA4 and a synthetic LX analog (Benzo-LXA4 ) as therapeutics in a murine model of diabetic kidney disease, ApoE-/- mice treated with streptozotocin...
February 28, 2018: Journal of the American Society of Nephrology: JASN
Jin Zhou, Fulin Liu, Luting Yu, Dan Xu, Bin Li, Guohui Zhang, Wen Huang, Lu Li, Yuanzhen Zhang, Wei Zhang, Hui Wang
Impaired placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity which inactivates maternal glucocorticoids is associated with poor fetal growth and a higher risk of chronic diseases in adulthood. This study aimed to elucidate the epigenetically regulatory mechanism of nicotine on placental 11β-HSD2 expression. Pregnant Wistar rats were administered 1.0 mg/kg nicotine subcutaneously twice a day from gestational day 9 to 20. The results showed that prenatal nicotine exposure increased corticosterone levels in the placenta and fetal serum, disrupted placental morphology and endocrine function, and reduced fetal bodyweight...
February 24, 2018: Toxicology and Applied Pharmacology
Subbiah Ramasamy, Ganesan Velmurugan, Balakrishnan Rekha, Sivakumar Anusha, K Shanmugha Rajan, Suresh Shanmugarajan, Tharmarajan Ramprasath, Pandi Gopal, Dhanendra Tomar, Karuppusamy V Karthik, Suresh Kumar Verma, Venkata Naga Srikanth Garikipati, Rajan Sudarsan
The physiological cardiac hypertrophy is an adaptive condition without myocyte cell death, while pathological hypertrophy is a maladaptive condition associated with myocyte cell death. This study explores the miRNome of α-2M-induced physiologically hypertrophied cardiomyocytes and the role of miRNA-99 family during cardiac hypertrophy. Physiological and pathological cardiac hypertrophy was induced in H9c2 cardiomyoblast cell lines using α-2M and isoproterenol respectively. Total RNA isolation and small RNA sequencing were executed for physiological hypertrophy model...
February 23, 2018: Experimental Cell Research
Cong Lu, Jingwei Lv, Liming Dong, Ning Jiang, Yan Wang, Qiong Wang, Yinghui Li, Shanguang Chen, Bei Fan, Fengzhong Wang, Xinmin Liu
20(S)-protopanaxatriol (PPT), one of the ginsenosides from Panax ginseng, has been reported to have neuroprotective effects and to improve memory. The present study was designed to investigate the protective effect of PPT on scopolamine-induced cognitive deficits in mice. Male Institute of Cancer Research mice were pretreated with 2 different doses of PPT (20 and 40 μmol/kg) for 27 days by intraperitoneal injection, and scopolamine (0.75 mg/kg) was injected intraperitoneally for 9 days to induce memory impairment...
February 22, 2018: Phytotherapy Research: PTR
P A Robinson-Drummer, T Chakraborty, N A Heroux, J B Rosen, M E Stanton
The context preexposure facilitation effect (CPFE) is a variant of contextual fear conditioning in which acquisition of the contextual representation and association of the retrieved contextual memory with an immediate foots-hock are separated by 24hrs. During the CPFE, learning- related expression patterns of the early growth response -1 gene (Egr-1) vary based on training phase and brain sub-region in adult and adolescent rats (Asok, Schreiber, Jablonski, Rosen, & Stanton, 2013; Shreiber et al., 2014; Chakraborty, Asok, Stanton, & Rosen, 2016)...
February 13, 2018: Neurobiology of Learning and Memory
Ting Sun, Yanmei Zhang, Shuping Zhong, Fenfei Gao, Yicun Chen, Bin Wang, Wenfeng Cai, Zhaojing Zhang, Weiqiu Li, Shishi Lu, Fuchun Zheng, Ganggang Shi
Early growth response-1 (Egr-1), a transcription factor which often underlies the molecular basis of myocardial ischemia/reperfusion (I/R) injury, and oxidative stress, is key to myocardial I/R injury. Silent information regulator of transcription 1(SIRT1) not only interacts with and is inhibited by Egr-1, but also downregulates reactive oxygen species (ROS) via the Forkhead box O1(FOXO1)/manganese superoxide dismutase (Mn-SOD) signaling pathway. N-n-butyl haloperidol iodide (F2), a new patented compound, protects the myocardium against myocardial I/R injury in various animal I/R models in vivo and various heart-derived cell hypoxia/reoxygenation (H/R) models in vitro...
2018: Frontiers in Pharmacology
Sunhwa Oh, Hyungjoo Kim, KeeSoo Nam, Incheol Shin
Egr-1 is known to function mainly as a tumor suppressor through direct regulation of multiple tumor suppressor genes. To determine the role of Egr-1 in breast tumors in vivo, we used mouse models of breast cancer induced by HER2/neu. We compared neu-overexpressing Egr-1 knockout mice (neu/Egr-1 KO) to neu-overexpressing Egr-1 wild type or heterozygote mice (neu/Egr-1 WT or neu/Egr-1 het) with regard to onset of tumor appearance and number of tumors per mouse. In addition, to examine the role of Egr-1 in vitro, we established neu/Egr-1 WT and KO tumor cell lines derived from breast tumors developed in each mouse...
February 2, 2018: Cellular Signalling
Cecilia Nyman, Stefan Fischer, Nadia Aubin-Horth, Barbara Taborsky
In vertebrates, the early social environment can persistently influence behaviour and social competence later in life. However, the molecular mechanisms underlying variation in animal social competence are largely unknown. In rats, high-quality maternal care causes an upregulation of hippocampal glucocorticoid receptors (gr) and reduces offspring stress responsiveness. This identifies gr regulation as a candidate mechanism for maintaining variation in animal social competence. We tested this hypothesis in a highly social cichlid fish, Neolamprologus pulcher, reared with or without caring parents...
January 31, 2018: Proceedings. Biological Sciences
Ivan Casaburi, Paola Avena, Arianna De Luca, Rosa Sirianni, Vittoria Rago, Adele Chimento, Francesca Trotta, Carmela Campana, William E Rainey, Vincenzo Pezzi
We previously demonstrated that treatment of the H295R adrenocortical cancer cell line with the non-steroidal, high-affinity GPER (G protein-coupled estrogen receptor 1) agonist G-1 reduced tumor growth in vitro and in vivo through a GPER independent action. Moreover, we observed that G-1 treatment induces cell-cycle arrest and apoptosis following a sustained ERK1/2 activation. However, the precise mechanisms causing these effects were not clarified. Starting from our preliminary published results, we performed a microarray study that clearly evidenced a strong and significative up-regulation of EGR-1 gene in H295R cells treated for 24h with micromolar concentration of G-1...
December 29, 2017: Oncotarget
Chih-Ying Lin, Lih-Yuan Lin
Zinc finger (ZF) motifs on proteins are frequently recognized as a structure for DNA binding. Accumulated reports indicate that ZF motifs contain nuclear localization signal (NLS) to facilitate the transport of ZF proteins into nucleus. We investigated the critical factors that facilitate the nuclear transport of triple C2H2 ZF proteins. Three conserved basic residues (hot spots) were identified among the ZF sequences of triple C2H2 ZF proteins that reportedly have NLS function. Additional basic residues can be found on the α-helix of the ZFs...
2018: PloS One
Lang Yi, Yan-Jun Lyn, Chong Peng, Rui-Li Zhu, Sha-Sha Bai, Liang Liu, Pei-Xun Wang, Hua Zhou, Yan Dong
Fibroblast like synoviocyte (FLS) is a crucial in the pathogenesis of rheumatoid arthritis (RA), and involved in inflammation and joint destruction. Sinomenine (SIN), an alkaloid derived from the plant Sinomenium acutum, has anti-inflammatory and analgesic effect and been used for RA treatment in China. Alpha 7 nicotinic acetylcholine receptors (α7nAChR), as the key receptor in cholinergic anti-inflammatory pathway (CAP) to inhibit inflammation, has been detected in RA patients synovium, but its role is still unclear...
January 20, 2018: International Immunopharmacology
Qing Yu, Qiaoying Huang, Xiaoxiao Du, Shao Xu, Mingtao Li, Shanshan Ma
The progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) is one of the hallmarks of Parkinson's disease (PD). Neuroinflammation has been proposed to contributes to the progressive nature of the disease. Early growth response-1 (Egr-1), a zinc finger transcription factor, has been shown to have a crucial role in both neuronal death and the inflammatory response. However, whether and how Egr-1 is involved in the pathogenesis of PD has not been investigated. Using the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD, we identified early peak induction of Egr-1 in the SNpc but not in the striatum...
January 11, 2018: Experimental Neurology
Hironori Fujiwara, Ryohei Tsushima, Ryo Okada, Suresh Awale, Ryota Araki, Takeshi Yabe, Kinzo Matsumoto
Social isolation (SI) mice exhibit behavioral abnormalities such as impairments of sociability- and attention-like behaviors, offering an animal model of neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD). This study aimed to identify the effects of Sansoninto (SST; suān zǎo rén tāng) on the psychiatric symptoms related to ADHD using SI mice. Four-week-old mice were socially isolated during the experimental period, and SST administration (800 or 2400 mg/kg, p.o.) was started at 2 weeks after starting SI...
January 2018: Journal of Traditional and Complementary Medicine
Dohyun Lee, Jinsun Lim, Kyung-Chul Woo, Kyong-Tai Kim
Epidermal growth factor (EGF) stimulates cell growth, proliferation, and survival. The biological benefits of EGF have been utilized in medical uses for improving wound healing as well as in today's skin cosmetics. EGF has been found in urine, saliva, milk, and plasma, but its efficient isolation remains a difficult task. With technical advances, recombinant protein purification technique has been used for EGF production. However, the recombinant EGF is still expensive and keeping it with stable activity is difficult to be used widely...
January 9, 2018: Scientific Reports
Gerald Thiel, Andrea Lesch, Sandra Rubil, Tobias M Backes, Oliver G Rössler
Transient receptor potential (TRP) channels belong to a heterogeneous superfamily of cation channels that are involved in the regulation of numerous biological functions, including regulation of Ca2+ and glucose homeostasis, tumorigenesis, temperature, and pain sensation. To understand the functions of TRP channels, their associated intracellular signaling pathways and molecular targets have to be identified on the cellular level. Stimulation of TRP channels frequently induces an influx of Ca2+ ions into the cells and the subsequent activation of protein kinases...
2018: International Review of Cell and Molecular Biology
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