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Guoyang Huang, Jiale Diao, Hongjie Yi, Li Xu, Jiajun Xu, Weigang Xu
Spinal cord injury (SCI) is a debilitating disease, effective prevention measures are in desperate need. Our previous work found that hyperbaric oxygen (HBO) preconditioning significantly protected rats from SCI after stimulated diving, and in vitro study further testified that HBO protected primary cultured rat spinal neurons from oxidative insult and oxygen glucose deprivation injury via heat shock protein (HSP) 32 induction. In this study, underlying molecular mechanisms were further investigated. The results showed that a single exposure to HBO significantly increased intracellular levels of reactive oxygen species (ROS) and nitric oxide (NO) and activated MEK1/2, ERK1/2, p38 MAPK, CREB, Bach1 and Nrf2...
September 24, 2016: Redox Biology
Huaping Li, Na Jiang, Qing Liu, Aili Gao, Xin Zhou, Bihua Liang, Runxiang Li, Zhenjie Li, Huilan Zhu
Ultraviolet (UV) radiation causes skin injury and inflammation resulting in impaired immune response and increased risk of skin cancer. It has been shown that green tea polyphenols (GTPs) enhanced intracellular antioxidant defense and promoted the downregulation of proapoptotic genes, and they could be used to protect against the damage induced by UV irradiation. However, the high instability and poor bioavailability of GTPs impose restrictions on their potential pharmacological use. Here we show that carboxymethyl cellulose sodium (CMC-Na) had a stabilizing effect on GTPs under aqueous conditions and topical application of GTPs (emulsified in CMC-Na) had a strong photoprotective effect against acute UVB induced photodamage in uncovered (Uncv) hairless mice skin...
October 5, 2016: Photochemical & Photobiological Sciences
Marta Pajares, Natalia Jiménez-Moreno, Ángel J García-Yagüe, Maribel Escoll, María L de Ceballos, Fred Van Leuven, Alberto Rábano, Masayuki Yamamoto, Ana I Rojo, Antonio Cuadrado
Autophagy is a highly coordinated process that is controlled at several levels including transcriptional regulation. Here, we identify the transcription factor NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2) as a regulator of autophagy gene expression and its relevance in a mouse model of Alzheimer disease (AD) that reproduces impaired APP (amyloid beta precursor protein) and human (Hs)MAPT/TAU processing, clearance and aggregation. We screened the chromatin immunoprecipitation database ENCODE for 2 proteins, MAFK and BACH1 that bind the NFE2L2-regulated enhancer antioxidant response element (ARE)...
July 18, 2016: Autophagy
Wenwen Wu, Yukiko Togashi, Yoshikazu Johmura, Yasuo Miyoshi, Sachihiko Nobuoka, Makoto Nakanishi, Tomohiko Ohta
The breast and ovarian cancer predisposition protein BRCA1 forms three mutually exclusive complexes with FANCJ (also called BACH1 or BRIP1), CtIP and Abraxas/RAP80 through its BRCT domains, while its RING domain binds to BARD1. We recently found that the interaction of HP1 with BARD1 is required for the accumulation of BRCA1 and CtIP at sites of DNA double-strand breaks (DSBs). Here, we investigated the importance of the HP1 and BARD1-HP1 interaction in the localization of FANCJ together with the other BRCA1-BRCT-binding proteins to clarify the separate role of the HP1-mediated pathway from the RNF8/RNF168-induced ubiquitin-mediated pathway for BRCA1 function...
July 11, 2016: Cancer Science
Chuanyang Su, Qiong Shi, Xiufang Song, Juanli Fu, Zixuan Liu, Yawen Wang, Yuxin Wang, Xiaomin Xia, Erqun Song, Yang Song
Our previous studies demonstrated that tetrachlorobenzoquinone (TCBQ), an active metabolite of pentachlorophenol, has effects on the generation of reactive oxygen species (ROS) and oxidative stress in vitro and in vivo. Nuclear factor erythroid-derived 2-like 2 (Nrf2) is a cellular sensor of electrophilic or oxidative stress that regulates the expression of antioxidant enzymes and defensive proteins. We have illustrated that TCBQ activates Nrf2 signaling by promoting the formation of the Kelch-like ECH-associated protein 1 (Keap1) cross-linking dimer and the formation of an ubiquitination switch from Nrf2 to Keap1...
July 1, 2016: Toxicology
Risa Ebina-Shibuya, Miki Watanabe-Matsui, Mitsuyo Matsumoto, Ari Itoh-Nakadai, Ryo Funayama, Keiko Nakayama, Akihiko Muto, Kazuhiko Igarashi
Pulmonary alveolar proteinosis (PAP) is a disease resulting from a dysfunction of the alveolar macrophages (AMs) where excess surfactant protein accumulates in the alveolar spaces. We previously reported that Bach2 KO mice developed PAP due to a defect in the handling of lipids by AMs. To investigate the functions of Bach1 and Bach2, which are regulated by oxidative stress, in the AMs and in lung homeostasis, we generated mice that lacked both Bach1 and Bach2 (Bach1/2 DKO mice). The Bach1/2 DKO mice showed more severe PAP phenotype than Bach2 KO mice with abnormal AMs, whereas the Bach1 KO mice did not develop any pulmonary disease...
July 7, 2016: Journal of Biochemistry
Hayato Go, Ping La, Fumihiko Namba, Masato Ito, Guang Yang, Andrey Brydun, Kazuhiko Igarashi, Phyllis A Dennery
In the lung, heme oxygenase-1 (HO-1) is developmentally regulated, with its highest expression in the first days of life. In addition, neonatal mice have limited HO-1 induction in hyperoxia compared with adults. However, few reports have addressed the functional effect of microRNAs (miRNAs) in the regulation of HO-1 in vivo. The aims of the present study were to characterize changes in lung miRNA expression during postnatal development and in response to hyperoxic exposure, and to identify miRNAs that target lung HO-1 gene expression...
August 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Manuj Ahuja, Navneet Ammal Kaidery, Lichuan Yang, Noel Calingasan, Natalya Smirnova, Arsen Gaisin, Irina N Gaisina, Irina Gazaryan, Dmitry M Hushpulian, Ismail Kaddour-Djebbar, Wendy B Bollag, John C Morgan, Rajiv R Ratan, Anatoly A Starkov, M Flint Beal, Bobby Thomas
UNLABELLED: A promising approach to neurotherapeutics involves activating the nuclear-factor-E2-related factor 2 (Nrf2)/antioxidant response element signaling, which regulates expression of antioxidant, anti-inflammatory, and cytoprotective genes. Tecfidera, a putative Nrf2 activator, is an oral formulation of dimethylfumarate (DMF) used to treat multiple sclerosis. We compared the effects of DMF and its bioactive metabolite monomethylfumarate (MMF) on Nrf2 signaling and their ability to block 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced experimental Parkinson's disease (PD)...
June 8, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Nir Rainy, Morad Zayoud, Yoel Kloog, Oded Rechavi, Itamar Goldstein
The two human lymphotrophic γ-herpesviruses, Kaposi's sarcoma herpesvirus (KSHV) and Epstein-Barr virus (EBV), are a recognized cause of human cancer, encoding multiple miRs that are major players in carcinogenesis. Previously, we discovered that EBV-encoded miRs transfer between infected B and T lymphocytes. To further explore the biological significance of the spreading of γ-herpesvirus-encoded miRs on carcinogenesis, we focused on KSHV-miR-K12-11 (miR-K12-11) that is unique in having an identical seed sequence with the oncomiR hsa-miR-155, implicated in B cell lymphomas development...
May 26, 2016: Oncotarget
Sadaf Davudian, Behzad Mansoori, Neda Shajari, Ali Mohammadi, Behzad Baradaran
BACH1 (BTB and CNC homology 1, basic leucine zipper transcription factor 1) is a transcriptional factor and a member of cap 'n' collar (CNC) and basic region leucine zipper factor family. In contrast to other bZIP family members, BACH1 appeared as a comparatively specific transcription factor. It acts as transcription regulator and is recognized as a recently hypoxia regulator and functions as an inducible repressor for the HO-1 gene in many human cell types in response to stress oxidative. In regard to studies lately, although, BACH1 has been related to the regulation of oxidative stress and heme oxidation, it has never been linked to invasion and metastasis...
August 15, 2016: Gene
Fumiki Katsuoka, Masayuki Yamamoto
The small Maf proteins (sMafs) are basic region leucine zipper (bZIP)-type transcription factors. The basic region of the Maf family is unique among the bZIP factors, and it contributes to the distinct DNA-binding mode of this class of proteins. MafF, MafG and MafK are the three vertebrate sMafs, and no functional differences have been observed among them in terms of their bZIP structures. sMafs form homodimers by themselves, and they form heterodimers with cap 'n' collar (CNC) proteins (p45 NF-E2, Nrf1, Nrf2, and Nrf3) and also with Bach proteins (Bach1 and Bach2)...
July 25, 2016: Gene
Xinhong Wang, Junxu Liu, Li Jiang, Xiangxiang Wei, Cong Niu, Rui Wang, Jianyi Zhang, Dan Meng, Kang Yao
The transcription factor BTB and CNC homology 1 (Bach1) regulates genes involved in the oxidative stress response and cell-cycle progression. We have recently shown that Bach1 impairs cell proliferation and promotes apoptosis in cultured endothelial cells (ECs), but the underlying mechanisms are largely uncharacterized. Here we demonstrate that Bach1 upregulation impaired the blood flow recovery from hindlimb ischemia and this effect was accompanied both by increases in reactive oxygen species (ROS) and cleaved caspase 3 levels and by declines in the expression of cyclin D1 in the injured tissues...
2016: Oxidative Medicine and Cellular Longevity
Yin Zhou, Haijing Wu, Ming Zhao, Christopher Chang, Qianjin Lu
The transcription factors Bach1 and Bach2, which belong to a basic region-leucine zipper (bZip) family, repress target gene expression by forming heterodimers with small Maf proteins. With the ability to bind to heme, Bach1 and Bach2 are important in maintaining heme homeostasis in response to oxidative stress, which is characterized by high levels of reactive oxygen species (ROS) in cells and thereby induces cellular damage and senescence. The inactivation of Bach1 exerts an antioxidant effect. Thus, Bach1 may be a potential therapeutic target of oxidative stress-related diseases...
June 2016: Clinical Reviews in Allergy & Immunology
Mitsuyo Matsumoto, Keiichi Kondo, Takuma Shiraki, Andrey Brydun, Ryo Funayama, Keiko Nakayama, Nobuo Yaegashi, Hideki Katagiri, Kazuhiko Igarashi
The transcription repressor BTB and CNC homology 1 (BACH1) represses genes involved in heme metabolism and oxidative stress response. BACH1 also suppresses the p53-dependent cellar senescence in primary mouse embryonic fibroblasts (MEFs). To investigate the role of BACH1 in MEF other than its known functions, we carried out a genomewide mapping of binding site for BACH1 and its heterodimer partner MAFK in immortalized MEFs (iMEFs) using chromatin immunoprecipitation and next-generation sequencing technology (ChIP-sequence)...
June 2016: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Q Luo, C Wu, S Sun, F Lu, L Xie, H Zhao, X Zhong, Q Zhou
The spatial-temporal expressions of bach1a, bach1b, bach2a and bach2b in early development of zebrafish Danio rerio embryos were examined in the present study by whole mount in situ hybridization. Transcripts of all genes were found at the one cell stage, suggesting that these four genes are maternally inherited. From the phylogenetic analyses, Bach1a and Bach1b from fishes form a well-supported group with two sub-groups. Bach2a and Bach2b, however, did not fall into one clade, suggesting that Bach2 proteins diverged faster or earlier than Bach1 proteins in fishes...
April 2016: Journal of Fish Biology
Kazuhiko Igarashi, Ari Itoh-Nakadai
The transcription repressor Bach2 is required for class switch recombination and somatic hypermutation of antibody genes in B cells, and proper development of effector and regulatory T cells. In addition, Bach2 and its related factor Bach1 promote B cell commitment of progenitor cells by repressing myeloid-related genes. Bach2 and the myeloid regulators C/EBPβ and C/EBPα mutually repress their expression, forming a gene regulatory network (GRN) that dictates the process of lineage commitment. Bach2 forms another GRN with the plasma cell regulator Blimp-1, in which Bach2 and Blimp-1 mutually repress their expression...
April 2016: Current Opinion in Immunology
Iris Ming-Jing Xu, Robin Kit-Ho Lai, Shu-Hai Lin, Aki Pui-Wah Tse, David Kung-Chun Chiu, Hui-Yu Koh, Cheuk-Ting Law, Chun-Ming Wong, Zongwei Cai, Carmen Chak-Lui Wong, Irene Oi-Lin Ng
Cancer cells experience an increase in oxidative stress. The pentose phosphate pathway (PPP) is a major biochemical pathway that generates antioxidant NADPH. Here, we show that transketolase (TKT), an enzyme in the PPP, is required for cancer growth because of its ability to affect the production of NAPDH to counteract oxidative stress. We show that TKT expression is tightly regulated by the Nuclear Factor, Erythroid 2-Like 2 (NRF2)/Kelch-Like ECH-Associated Protein 1 (KEAP1)/BTB and CNC Homolog 1 (BACH1) oxidative stress sensor pathway in cancers...
February 9, 2016: Proceedings of the National Academy of Sciences of the United States of America
Henry Jay Forman, Kelvin J A Davies
No abstract text is available yet for this article.
March 2016: Free Radical Biology & Medicine
Minggang Fang, Lloyd Hutchinson, April Deng, Michael R Green
During cancer development, it is well established that many genes, including tumor suppressor genes, are hypermethylated and transcriptionally repressed, a phenomenon referred to as epigenetic silencing. In general, the factors involved in, and the mechanistic basis of, epigenetic silencing during cancer development are not well understood. We have recently described an epigenetic silencing pathway, directed by the oncogenic B-Raf proto-oncogene (BRAF) variant BRAF(V600E), that mediates widespread epigenetic silencing in colorectal cancer (CRC)...
February 2, 2016: Proceedings of the National Academy of Sciences of the United States of America
Qian Wu, Atanu Paul, Dan Su, Shahid Mehmood, Tzeh Keong Foo, Takashi Ochi, Emma L Bunting, Bing Xia, Carol V Robinson, Bin Wang, Tom L Blundell
BRCA1 accumulation at DNA damage sites is an important step for its function in the DNA damage response and in DNA repair. BRCA1-BRCT domains bind to proteins containing the phosphorylated serine-proline-x-phenylalanine (pSPxF) motif including Abraxas, Bach1/FancJ, and CtIP. In this study, we demonstrate that ionizing radiation (IR)-induces ATM-dependent phosphorylation of serine 404 (S404) next to the pSPxF motif. Crystal structures of BRCT/Abraxas show that phosphorylation of S404 is important for extensive interactions through the N-terminal sequence outside the pSPxF motif and leads to formation of a stable dimer...
February 4, 2016: Molecular Cell
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