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Tahmina Islam, Ajit Ghosh
Reactive carbonyl species, such as methylglyoxal and glyoxal are very toxic in nature and can inactivate various cellular macromolecules such as DNA, RNA, and protein by forming advanced glycation end products. Conventional glyoxalase pathway with two enzymes- glyoxalase I and glyoxalase II, detoxify MG into D-lactate with the help of reduced glutathione. However, DJ-1/PfpI domain(s) containing DJ-1/ Hsp31 proteins do the same in a single step, and thus termed as "glyoxalase III". A comprehensive genome-wide analysis of soybean identified eleven putative glyoxalase III proteins with DJ-1/PfpI domain encoded by seven genes...
March 19, 2018: Scientific Reports
Takuya Yamane, Izumi Kato-Ose, Tatsuji Sakamoto, Yoshihisa Nakano
Background: Asparaginyl endopeptidase, also known as legumain (EC shows strong activity in the mouse kidney. Legumain is also highly expressed in tumors. DJ-1/PARK7 is a Parkinson's disease- and cancer-associated protein. DJ-1 is a coactivator of various transcription factors. Recently, we reported that transcription of the legumain gene is regulated by p53 through DJ-1. Methods: We measured the secretion levels of legumain in a conditioned medium of DJ-1 knockout cells and in serum from DJ-1 knockout mice using Western blotting and ELISA...
2018: Open Biochemistry Journal
Roshan Kumar, Raniki Kumari, Sanjay Kumar, Deepak Kumar Jangir, Tushar Kanti Maiti
α-Synuclein, a major constituent of proteinaceous inclusions named Lewy body, has been shown to be released and taken up by cells, which may facilitate its progressive pathological spreading and neuronal cell death in Parkinson's disease. However, the pathophysiological effect and signalling cascade initiated by extracellular α-synuclein in cellular milieu are not well understood. Herein we have investigated the perturbations induced by low molecular weight α-synuclein and different types of α-synuclein oligomers in the neuroblastoma SH-SY5Y cells...
March 14, 2018: Biomacromolecules
George Vavougios, Sotirios G Zarogiannis, Triantafylos Doskas
Recent research has outlined that Dimethyl Fumarate (DMF) functions as a gene regulator via multiple pathways, critical among which is the NRF2 cytoprotective cascade. PARK7/DJ-1 is a multifunctional protein that acts as a redox sensor and effector of multiple cytoprotective pathways, including NRF2. Specifically, it prevents the association of NRF2 with its inhibitor KEAP1, allowing NRF2 to enter the nucleus and mediate cytoprotective and antioxidant cascades. It is our hypothesis that while the NRF2-KEAP1 inhibitory complex is reported the main pharmacological target for DMF's NRF dependent functions, no study to date has explored the effects of DMF on DJ-1's expression, and vice-versa, the possibility of a regulatory inadequacy in the upstream, oxidant-responsive DJ-1 activator of the NRF2 cascade...
February 26, 2018: Multiple Sclerosis and related Disorders
Ann Kristin Frøyset, Amanda J Edson, Naouel Gharbi, Essa A Khan, Daniel Dondorp, Qing Bai, Ettore Tiraboschi, Maximiliano L Suster, Joanne B Connolly, Edward A Burton, Kari E Fladmark
DJ-1, a Parkinson's disease-associated protein, is strongly up-regulated in reactive astrocytes in Parkinson's disease. This is proposed to represent a neuronal protective response, although the mechanism has not yet been identified. We have generated a transgenic zebrafish line with increased astroglial DJ-1 expression driven by regulatory elements from the zebrafish GFAP gene. Larvae from this transgenic line are protected from oxidative stress-induced injuries as caused by MPP+ , a mitochondrial complex I inhibitor shown to induce dopaminergic cells death...
February 17, 2018: Redox Biology
Kang Pa Lee, Suji Baek, Seung Hyo Jung, Long Cui, Donghyen Lee, Dong-Youb Lee, Wahn Soo Choi, Hyun Woo Chung, Byeong Han Lee, Bokyung Kim, Kyung Jong Won
DJ-1 and sphingosine-1-phosphate (S1P) receptors (S1PRs) are implicated in the control of physiology and pathophysiology of cardiovascular systems such as blood pressure, atherosclerosis, and restenosis. Here, we investigated whether DJ-1 with antioxidant function participates in the regulation of S1PR1 and S1PR2 expression in vascular smooth muscle cells (VSMCs) and whether this response is related to vascular neointima formation. In vitro studies used cellular migration assay, western blot, reverse transcriptase and real-time PCR analysis, and immunocytochemistry...
March 6, 2018: Pflügers Archiv: European Journal of Physiology
Nathaniel Edward Bennett Saidu, Marie Bretagne, Audrey Lupo Mansuet, Pierre-Alexandre Just, Karen Leroy, Olivier Cerles, Sandrine Chouzenoux, Carole Nicco, Diane Damotte, Marco Alifano, Bruno Borghese, François Goldwasser, Frédéric Batteux, Jérôme Alexandre
KRAS mutation, one of the most common molecular alterations observed in adult carcinomas, was reported to activate the anti-oxidant program driven by the transcription factor NRF2 (Nuclear factor-erythroid 2-related factor 2). We previously observed that the antitumoral effect of Dimethyl fumarate (DMF) is dependent of NRF2 pathway inhibition. We used in vitro methods to examine the effect of DMF on cell death and the activation of the NRF2/DJ-1 antioxidant pathway. We report here that DMF is preferentially cytotoxic against KRAS mutated cancer cells...
February 6, 2018: Oncotarget
Lior Molcho, Tali Ben-Zur, Yael Barhum, Daniel Offen
Stroke is a leading cause of death worldwide and inflicts serious long-term damage and disability. The vasoconstrictor Endothelin-1, presenting long-term neurological deficits associated with excitotoxicity and oxidative stress is being increasingly used to induce focal ischemic injury as a model of stroke. A DJ-1 based peptide named ND-13 was shown to protect against glutamate toxicity, neurotoxic insults and oxidative stress in various animal models. Here we focus on the benefits of treatment with ND-13 on the functional outcome of focal ischemic injury...
2018: PloS One
Jason F Cooper, Jeremy M Van Raamsdonk
Parkinson's disease (PD) is an adult onset neurodegenerative disease that is characterized by selective degeneration of neurons primarily in the substantia nigra. At present, the pathogenesis of PD is incompletely understood and there are no neuroprotective treatments available. Accurate animal models of PD provide the opportunity to elucidate disease mechanisms and identify therapeutic targets. This review focuses on C. elegans models of PD, including both genetic and toxicant models. This microscopic worm offers several advantages for the study of PD including ease of genetic manipulation, ability to complete experiments rapidly, low cost, and ability to perform large scale screens for disease modifiers...
2018: Journal of Parkinson's Disease
S Lundin, C F Wahlgren, A Bergström, E K Johansson, E Dahlén, N Andersson, I Kull
BACKGROUND: Knowledge regarding how adolescents treat their eczema is sparse. OBJECTIVES: To explore the use of emollients and topical glucocorticoids in adolescents with eczema in relation to sex and disease severity, and to study dispensing patterns of topical glucocorticoids. METHODS: Questionnaire-based data on symptoms of eczema, eczema severity and treatment with emollients and topical glucocorticoids were obtained from 3,108 adolescents in the Swedish population-based birth cohort BAMSE...
February 25, 2018: British Journal of Dermatology
Li Hui Tan, Karim Bahmed, Chih-Ru Lin, Nathaniel Marchetti, Sudhir Bolla, Gerard J Criner, Steven Kelsen, Muniswamy Madesh, Beata Kosmider
Emphysema is characterized by irreversibly enlarged airspaces and destruction of alveolar walls. One of the factors contributing to this disease pathogenesis is an elevation in extracellular matrix (ECM) degradation in the lung. Alveolar type II (ATII) cells produce and secrete pulmonary surfactants and proliferate to restore the epithelium after damage. We isolated ATII cells from control non-smokers, smokers and patients with emphysema to determine the role of NFE2 (nuclear factor, erythroid-derived 2). NFE2 is a heterodimer composed of two subunits, a 45 kDa (p45 NFE2) and 18 kDa (p18 NFE2) polypeptides...
February 23, 2018: Scientific Reports
Thais Ceresér Vilela, Pauline Souza Effting, Giulia Dos Santos Pedroso, Hemelin Farias, Lara Paganini, Helen Sorato Rebelo, Renata Tiescoski Nesi, Vanessa Moraes de Andrade, Ricardo Aurino de Pinho
Skeletal muscle aging is associated with loss of mass, function, and strength-a condition known as sarcopenia. It has been reported that sarcopenia can be attenuated by physical exercise. Therefore, we investigated whether 2 different physical exercise protocols could modulate and induce changes in oxidative and inflammatory parameters, as well as in BDNF and DNA repair enzyme levels in skeletal muscle tissue of aged rats. Aging Wistar rats performed treadmill or strength training for 50 min 3 to 4 times a week for 8 weeks...
February 19, 2018: Experimental Gerontology
Yukiko Tabata, Yoshitsugu Nakanishi, Kanako C Hatanaka, Yutaka Hatanaka, Takahiro Tsuchikawa, Keisuke Okamura, Takehiro Noji, Toshiaki Shichinohe, Yoshihiro Matsuno, Satoshi Hirano
We have previously reported that DJ-1 protein is up-regulated in cholangiocarcinoma compared with non-neoplastic epithelium of the bile duct in a study using liquid chromatography mass spectrometry-based proteomics. The aim of this study was to clarify whether DJ-1 expression offers a biomarker for patients with invasive extrahepatic cholangiocarcinoma (EHCC) who undergo surgical resection with curative intent. Positive immunohistochemical (IHC) staining of DJ-1 was significantly more frequent in the cytoplasm of 96 invasive EHCCs (n=28, 29...
February 12, 2018: Human Pathology
Yong Lin, Qian Chen, Quan-Xing Liu, Dong Zhou, Xiao Lu, Xu-Feng Deng, Hua Yang, Hong Zheng, Yuan Qiu
Cancer cell invasion and unlimited proliferation are key factors in patients with colorectal cancer (CRC). Increased protein deglycase DJ-1 in cancer cells is known to promote tumor growth; however, its role in CRC progression is not well defined. In this study, we investigated 100 CRC patients with disease stages I-IV to determine whether DJ-1 could serve as a prognostic biomarker in CRC. These results showed that DJ-1 expression in CRC tissues was higher than that in normal colon tissues and was associated with the (Tumor Node Metastasis) TNM stage...
February 14, 2018: Cancer Medicine
Hao Ding, Xing-Wang Xu, Huan Wang, Lin Xiao, Le Zhao, Guang-Ling Duan, Xiao-Ran Li, Zhao-Xia Ma, He-Ping Chen
DJ-1 was recently reported to mediate the cardioprotection of delayed hypoxic preconditioning (DHP) by suppressing hypoxia/reoxygenation (H/R)-induced oxidative stress, but its mechanism against H/R-induced oxidative stress during DHP is not fully elucidated. Here, using the well-established cellular model of DHP, we again found that DHP significantly improved cell viability and reduced lactate dehydrogenase release with concurrently up-regulated DJ-1 protein expression in H9c2 cells subjected to H/R. Importantly, DHP efficiently improved mitochondrial complex I activity following H/R and attenuated H/R-induced mitochondrial reactive oxygen species (ROS) generation and subsequent oxidative stress, as demonstrated by a much smaller decrease in reduced glutathione/oxidized glutathione ratio and a much smaller increase in intracellular ROS and malondialdehyde contents than that observed for the H/R group...
February 12, 2018: Cell Biochemistry and Function
Rose B Creed, Matthew S Goldberg
Preclinical research on Parkinson's disease has relied heavily on mouse and rat animal models. Initially, PD animal models were generated primarily by chemical neurotoxins that induce acute loss of dopaminergic neurons in the substantia nigra. On the discovery of genetic mutations causally linked to PD, mice were used more than rats to generate laboratory animals bearing PD-linked mutations because mutagenesis was more difficult in rats. Recent advances in technology for mammalian genome engineering and optimization of viral expression vectors have increased the use of genetic rat models of PD...
February 8, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
Neha Mishra, Sonam Lata, Priyanka Deshmukh, Kajal Kamat, Avadhesha Surolia, Tanushree Banerjee
Cellular stress like ER and oxidative stress are the principle causative agents of various proteinopathies. Multifunctional protein PARK7/DJ-1 provides protection against cellular stress. Recently, insulin/IGF also has emerged as a neuro-protective molecule. However, it is not known whether DJ-1 and insulin/IGF complement each other for cellular protection in response to stress. In this study, we show for the first time, that in human and mouse neuronal cell lines, down regulation of DJ-1 for 48 h leads to compensatory upregulation of insulin/IGF signaling (IIS) pathway genes, namely, insulin receptor, insulin receptor substrate, and Akt under normal physiological conditions as well as in cellular stress conditions...
February 7, 2018: BioFactors
Jae Won Kyung, Jin-Mo Kim, Wongyoung Lee, Tae-Young Ha, Seon-Heui Cha, Kyung-Hwun Chung, Dong-Joo Choi, Ilo Jou, Woo Keun Song, Eun-Hye Joe, Sung Hyun Kim, Sang Myun Park
Mutations in DJ-1 (PARK7) are a known cause of early-onset autosomal recessive Parkinson's disease (PD). Accumulating evidence indicates that abnormalities of synaptic vesicle trafficking underlie the pathophysiological mechanism of PD. In the present study, we explored whether DJ-1 is involved in CNS synaptic function. DJ-1 deficiency impaired synaptic vesicle endocytosis and reavailability without inducing structural alterations in synapses. Familial mutants of DJ-1 (M26I, E64D, and L166P) were unable to rescue defective endocytosis of synaptic vesicles, whereas WT DJ-1 expression completely restored endocytic function in DJ-1 KO neurons...
January 31, 2018: Proceedings of the National Academy of Sciences of the United States of America
Gábor Koncsos, Zoltán V Varga, Tamás Baranyai, Péter Ferdinandy, Rainer Schulz, Zoltán Giricz, Kerstin Boengler
INTRODUCTION: In the heart, subsarcolemmal (SSM), interfibrillar (IFM) and perinuclear mitochondria represent three subtypes of mitochondria. The most commonly used protease during IFM isolation is the nagarse, however, its effect on the detection of mitochondrial proteins is still unclear. Therefore, we investigated whether nagarse treatment influences the quantification of mitochondrial proteins. METHODS: SSM and IFM were isolated from hearts of mice and rats...
January 26, 2018: Journal of Pharmacological and Toxicological Methods
S B Larsen, Z Hanss, R Krüger
Mitochondrial impairment is a well-established pathological pathway implicated in Parkinson's disease (PD). Defects of the complex I of the mitochondrial respiratory chain have been found in post-mortem brains from sporadic PD patients. Furthermore, several disease-related genes are linked to mitochondrial pathways, such as PRKN, PINK1, DJ-1 and HTRA2 and are associated with mitochondrial impairment. This phenotype can be caused by the dysfunction of mitochondrial quality control machinery at different levels: molecular, organellar or cellular...
January 25, 2018: Cell and Tissue Research
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