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Yeo Jin Kim, Hyoung-June Kim, Hye Lim Kim, Hyo Jeong Kim, Hyun Soo Kim, Tae Ryong Lee, Dong Wook Shin, Young Rok Seo
The phototherapeutic effects of visible red light on skin have been extensively investigated, but the underlying biological mechanisms remain poorly understood. We aimed to elucidate the protective mechanism of visible red light in terms of DNA repair of UV-induced oxidative damage in normal human dermal fibroblasts. The protective effect of visible red light on UV-induced DNA damage was identified by several assays in both two-dimensional and three-dimensional cell culture systems. With regard to the protective mechanism of visible red light, our data showed alterations in base excision repair (BER) mediated by growth arrest and DNA damage inducible, alpha (GADD45A)...
October 8, 2016: Journal of Investigative Dermatology
Nora Bengoa-Vergniory, Irantzu Gorroño-Etxebarria, Inmaculada López-Sánchez, Michele Marra, Pierluigi Di Chiaro, Robert Kypta
Wnt proteins preferentially activate either β-catenin-dependent or β-catenin-independent signals, but the activity of a particular Wnt also depends on cellular context and receptor availability. We previously reported that Wnt-3a induces neural differentiation of human embryonic stem cell-derived neural stem cells (NSCs) in a β-catenin-independent manner by activating a signal involving JNK and the AP-1 family member ATF-2. Here, we report the results of a gene silencing approach to identify the Wnt receptors that mediate this response to Wnt-3a...
October 5, 2016: Molecular Neurobiology
Ila Pant, S Girish Rao, Paturu Kondaiah
Oral submucous fibrosis (OSF) is potentially premalignant with progressive and irreversible extracellular matrix deposition accompanied by epithelial atrophy and like other fibrotic disorders, is primarily a TGF-β driven disease. OSF is caused by prolonged chewing of areca nut. Our previous studies reported a pivotal role for TGF-β activation and its effects contributing to OSF. However, the mechanism for activation of TGF-β signaling in OSF is still unknown. In this study we demonstrate activation of TGF-β signaling with sub-cytotoxic dose of areca nut in epithelial cells and discovered a key role for pJNK in this process...
October 6, 2016: Scientific Reports
X Liu, Y Sun, L Yue, S Li, X Qi, H Zhao, Y Yang, C Zhang, H Yu
Ginsenoside Rh2 has been shown to have an anti-tumor effect on a wide range of cancers. A previous study has shown that ginsenoside Rh2 can inhibit the proliferation of the human lung adenocarcinoma A549 cell line in a dose-dependent manner by activating caspase-8/3 activity to promote apoptosis. However, the association of the JNK signaling pathways and transcription factors with ginsenoside Rh2 in the suppression of non-small cell lung cancer has not yet been reported. In this study, we found that ginsenoside Rh2 can activate the JNK/MAPKs signaling pathway and increase the phosphorylation and transcriptional activity of the transcription factors AP-1 and ATF2...
September 19, 2016: Genetics and Molecular Research: GMR
Smitha Bhat, Sandeep Mallya, Vinay Koshy Varghese, Pradyumna Jayaram, Sanjiban Chakrabarty, Kalpana S Joshi, Tanuja M Nesari, Kapaettu Satyamoorthy
With a purpose of accurate and simultaneous determination of DNA methylation from multiple loci in multiple samples, here, we are demonstrating a method to aid rapid DNA methylation detection of genomic sequences. Using genomic DNA of peripheral blood from 14 healthy individuals, DNA methylation in 465 CpG sites from 12 loci of genes (ADAM22, ATF2, BCR, CD83, CREBBP, IL12B, IL17RA, MAP2K2, RBM38, TGFBR2, TGFBR3, and WNT5A) was analysed by targeted next generation bisulfite sequencing. Analysed region for three genes, BCR, IL17RA and RBM38 showed an absolute mean DNA methylation of 25...
December 15, 2016: Gene
Dena A J Ahmad, Ola H Negm, M Layth Alabdullah, Sameer Mirza, Mohamed R Hamed, Vimla Band, Andrew R Green, Ian O Ellis, Emad A Rakha
BACKGROUND: Mitogen-activated protein kinases (MAPKs) are signalling transduction molecules that have different functions and diverse behaviour in cancer. In breast cancer, MAPK is related to oestrogen receptor (ER) and HER2. METHODS: Protein expression of a large panel of MAPKs (JNK1/2, ERK, p38, C-JUN and ATF2 including phosphorylated forms) were assessed immunohistochemically in a large (n = 1400) and well-characterised breast cancer series prepared as tissue microarray...
October 2016: Breast Cancer Research and Treatment
Shiwei Song, Abul Fajol, Xiankun Tu, Baogang Ren, Songsheng Shi
In human cancers, miRNAs are important regulators of multiple cellular processes, and aberrant miRNA expression has been observed, and their alterations contribute to multiple cancer development and progression. Till now, little has been known about the role of miR-204 in human glioblastoma (GBM). In the present study, we used in-vitro assays to investigate the mechanisms of miR-204 in GBM cell lines and 60 cases of GBM tissues. Here, we found that miR-204 expression is downregulated in both GBM cell lines A172, U87 and U251 cells and GBM tissues as compared with NHA cells and normal tissues (all p<0...
August 31, 2016: Oncotarget
Hironori Nishitsuji, Saneyuki Ujino, Sachiyo Yoshio, Masaya Sugiyama, Masashi Mizokami, Tatsuya Kanto, Kunitada Shimotohno
Despite the breadth of knowledge that exists regarding the function of long noncoding RNAs (lncRNAs) in biological phenomena, the role of lncRNAs in host antiviral responses is poorly understood. Here, we report that lncRNA#32 is associated with type I IFN signaling. The silencing of lncRNA#32 dramatically reduced the level of IFN-stimulated gene (ISG) expression, resulting in sensitivity to encephalomyocarditis virus (EMCV) infection. In contrast, the ectopic expression of lncRNA#32 significantly suppressed EMCV replication, suggesting that lncRNA#32 positively regulates the host antiviral response...
September 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
Chen Li, Yu Zhou, Anastacia Loberg, Stanley M Tahara, Punam Malik, Vijay K Kalra
Previous studies showed higher levels of placenta growth factor (PlGF) correlated with increased plasma levels of endothelin-1 (ET-1), a potent vasoconstrictor, in sickle cell disease (SCD). PlGF mediated transcription of ET-1 occurred by activation of HIF-1α, and post-transcriptionally by miR-199a2, which targets the 3' -UTR of HIF-1α mRNA. However, relatively less is known how PlGF represses the expression of miR-199a2 located in the DNM3os transcription unit. Here we show PlGF induces the expression of ATF3, which in association with accessory proteins (JDP2, ATF2 and HDAC6), as determined by proteomic analysis, bind to the DNM3os promoter...
August 29, 2016: Molecular and Cellular Biology
Yang Liu, Toshio Maekawa, Keisuke Yoshida, Tamio Furuse, Hideki Kaneda, Shigeharu Wakana, Shunsuke Ishii
The activating transcription factor (ATF)2 family of transcription factors regulates a variety of metabolic processes, including adipogenesis and adaptive thermogenesis. ATF7 is a member of the ATF2 family, and mediates epigenetic changes induced by environmental stresses, such as social isolation and pathogen infection. However, the metabolic role of ATF7 remains unknown. The aim of the present study is to examine the role of ATF7 in metabolism using ATF7-dificeint mice. Atf7(-/-) mice exhibited lower body weight and resisted diet-induced obesity...
September 16, 2016: Biochemical and Biophysical Research Communications
Mariangela De Robertis, Luisa Loiacono, Caterina Fusilli, Luana Maria Poeta, Tommaso Mazza, Massimo Sanchez, Luigi Marchionni, Emanuela Signori, Giuseppe Lamorte, Angelo Vescovi, Vito M Fazio, Jesus Garcia-Foncillas
PURPOSE: EphA2 receptor is involved in multiple cross-talks with other cellular networks including EGFR, FAK and VEGF pathways, with which it collaborates to stimulate cell migration, invasion and metastasis. Colorectal cancer (CRC) EphA2 overexpression has also been correlated to stem-like properties of cells and tumor malignancy. We investigated the molecular crosstalk and microRNAs modulation of the EphA2 and EGFR pathways. We also explored the role of EphA2/EGFR pathway mediators as prognostic factors or predictors of cetuximab benefit in CRC patients...
July 11, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Deng-Shuang Wu, Cheng Chen, Zhen-Jie Wu, Bing Liu, Li Gao, Qing Yang, Wei Chen, Jun-Ming Chen, Yi Bao, Le Qu, Lin-Hui Wang
BACKGROUND: Activating transcription factor 2 (ATF2) is a basic helix-loop-helix transcription factor, which has been shown to participate in the pathobiology of numerous cancers. However, the role of ATF2 in renal cell carcinoma (RCC) remains unclear. METHODS: ATF2 knockdown and overexpression studies were performed in RCC cells to evaluate changes in cell viability, cell cycle, apoptosis, migration and invasion. Xenograft models were used to examine the tumorigenic and metastatic capability of RCC cells upon ATF2 suppression...
2016: Journal of Experimental & Clinical Cancer Research: CR
Jiri Stribny, Amparo Querol, Roberto Pérez-Torrado
Higher alcohols and acetate esters belong to the most important yeast secondary metabolites that significantly contribute to the overall flavor and aroma profile of fermented products. In Saccharomyces cerevisiae, esterification of higher alcohols is catalyzed mainly by the alcohol acetyltransferases encoded by genes ATF1 and ATF2. Previous investigation has shown other Saccharomyces species, e.g., S. kudriavzevii and S. uvarum, to vary in aroma-active higher alcohols and acetate esters formation when compared to S...
2016: Frontiers in Microbiology
Leonie von Elsner, Sandra Hagemann, Ingo Just, Astrid Rohrbeck
C3 exoenzyme from C. botulinum is an ADP-ribosyltransferase that inactivates selectively RhoA, B, and C by coupling an ADP-ribose moiety. Rho-GTPases are involved in various cellular processes, such as regulation of actin cytoskeleton, cell proliferation, and apoptosis. Previous studies of our group with the murine hippocampal cell line HT22 revealed a C3-mediated inhibition of cell proliferation after 48 h and a prevention of serum-starved cells from apoptosis. For both effects, alterations of various signaling pathways are already known, including also changes on the transcriptional level...
September 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
Jimin Zhao, Junfen Ma, Jing Lu, Yanan Jiang, Yanyan Zhang, Xiaoyan Zhang, Jun Zhao, Hongyan Yang, Youtian Huang, Mingyao Zhao, Kangdong Liu, Ziming Dong
Base excision repair (BER) systems are important for maintaining the integrity of genomes in mammalian cells. Aberrant DNA bases or broken single strands can be repaired by BER. Consequently, DNA lesions, which may be caused by cancer and aging, have a close association with BER procedure. DNA polymerase β (polβ) is a critical BER enzyme that can excise 5'-sugar phosphate prior to adding a nucleotide in the gap by its function as a DNA polymerase in the BER process. However, DNA polβ is an error-prone DNA polymerase, and overexpressing polβ increases the cellular spontaneous mutation rate...
July 2016: Oncology Letters
Giuseppina Claps, Yann Cheli, Tongwu Zhang, Marzia Scortegagna, Eric Lau, Hyungsoo Kim, Jianfei Qi, Jian-Liang Li, Brian James, Andreas Dzung, Mitchell P Levesque, Reinhard Dummer, Nicholas K Hayward, Marcus Bosenberg, Kevin M Brown, Ze'ev A Ronai
Melanoma is one of the most lethal cutaneous malignancies, characterized by chemoresistance and a striking propensity to metastasize. The transcription factor ATF2 elicits oncogenic activities in melanoma, and its inhibition attenuates melanoma development. Here, we show that expression of a transcriptionally inactive form of Atf2 (Atf2(Δ8,9)) promotes development of melanoma in mouse models. Atf2(Δ8,9)-driven tumors show enhanced pigmentation, immune infiltration, and metastatic propensity. Similar to mouse Atf2(Δ8,9), we have identified a transcriptionally inactive human ATF2 splice variant 5 (ATF2(SV5)) that enhances the growth and migration capacity of cultured melanoma cells and immortalized melanocytes...
May 31, 2016: Cell Reports
Hyeon-Ju Jeong, Hye-Jin Lee, Tuan Anh Vuong, Kyu-Sil Choi, Dahee Choi, Sung-Hoi Koo, Sung Chun Cho, Hana Cho, Jong-Sun Kang
Maintenance of skeletal muscle function is critical for metabolic health and the disruption of which exacerbates many chronic diseases such as obesity and diabetes. Skeletal muscle responds to exercise or metabolic demands by a fiber-type switch regulated by signaling-transcription networks that remains to be fully defined. Here, we report that protein arginine methyltransferase 7 (Prmt7) is a key regulator for skeletal muscle oxidative metabolism. Prmt7 is expressed at the highest levels in skeletal muscle and decreased in skeletal muscles with age or obesity...
July 2016: Diabetes
Kristoffer Krogerus, Mikko Arvas, Matteo De Chiara, Frederico Magalhães, Laura Mattinen, Merja Oja, Virve Vidgren, Jia-Xing Yue, Gianni Liti, Brian Gibson
The genomes of hybrid organisms, such as lager yeast (Saccharomyces cerevisiae × Saccharomyces eubayanus), contain orthologous genes, the functionality and effect of which may differ depending on their origin and copy number. How the parental subgenomes in lager yeast contribute to important phenotypic traits such as fermentation performance, aroma production, and stress tolerance remains poorly understood. Here, three de novo lager yeast hybrids with different ploidy levels (allodiploid, allotriploid, and allotetraploid) were generated through hybridization techniques without genetic modification...
August 2016: Applied Microbiology and Biotechnology
Bhaswati Banerjee, Pinki Nandi, Supriya Chakraborty, Sanghamitra Raha, Parimal C Sen, Kuladip Jana
Benzo(a)pyrene [B(a)P] is an environmental toxicant that alters the steroidogenic profile of testis and induces testicular dysfunction. In the present study, we have investigated the molecular signaling of B(a)P and the ameliorative potential of the natural aryl hydrocarbon receptor (AhR) antagonist and antioxidant, resveratrol, on B(a)P-induced male reproductive toxicity. Studies showed that B(a)P treatment resulted in p38 MAPK activation and increased inducible nitric oxide synthase (iNOS) production along with testicular apoptosis and steroidogenic dysfunction...
August 2016: Journal of Nutritional Biochemistry
S Pereira, W Q Yu, J Moore, Y Mori, E Tsiani, A Giacca
The mechanisms whereby prolonged plasma free fatty acids elevation, as found in obesity, causes hepatic insulin resistance are not fully clarified. We herein investigated whether inhibition of p38 mitogen-activated protein kinase (MAPK) prevented hepatic insulin resistance following prolonged lipid infusion. Chronically cannulated rats were subdivided into one of four intravenous (i.v.) treatments that lasted 48 h: Saline (5.5 μl min(-1)), Intralipid plus heparin (IH, 20% Intralipid+20 U ml(-1) heparin; 5...
2016: Nutrition & Diabetes
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