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https://www.readbyqxmd.com/read/27903648/evidence-against-a-role-for-the-parkinsonism-associated-protein-dj-1-in-methylglyoxal-detoxification
#1
Daniel H Pfaff, Thomas Fleming, Peter Nawroth, Aurelio A Teleman
Methylglyoxal (MG) is a reactive metabolite that forms adducts on lysine and arginine residues of proteins, thereby affecting their function. Methylglyoxal is detoxified by the Glyoxalase system, consisting of two enzymes, Glo1 and Glo2, that act sequentially to convert MG into D-lactate. Recently, the Parkinsonism-associated protein DJ-1 was described in vitro to have glyoxalase activity, thereby detoxifying the MG metabolite, or deglycase activity, thereby removing the adduct formed by MG on proteins. Since Drosophila is an established model system to study signaling, neurodegeneration and metabolic regulation in vivo, we asked whether DJ-1 contributes to MG detoxification in vivo...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27868407/-effect-of-dj-1-silencing-by-rna-interference-on-growth-of-xenografted-human-laryngeal-squamous-cell-carcinoma-hep-2-cells-in-nude-mice
#2
Zhisen Shen, Hongxia Deng, Dong Ye, Jian Zhang, Shijie Qiu, Qun Li, Xiang Cui
Objective: To investigate the effect of silencing DJ-1 on xenografted human laryngeal squamous cell carcinoma (LSCC) Hep-2 cells in nude mice. Methods: Xenograft model of human LSCC was established by subcutaneous transplantation of Hep-2 cells in 24 nude mice. The LSCC-bearing nude mice were randomly divided into 3 groups (n=8 in each):DJ-1 siRNA low dose group and DJ-1 siRNA high dose group were injected in tumors with 20 μg of DJ-1 siRNA or 40 μg of DJ-1 siRNA in 50 μL, respectively; control group was injected with 5% glucose solution in 50 μL, twice a week for 3 weeks...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/27845899/bisdemethoxycurcumin-exerts-pro-apoptotic-effects-in-human-pancreatic-adenocarcinoma-cells-through-mitochondrial-dysfunction-and-a-grp78-dependent-pathway
#3
Haopeng Yang, Shengjun Fan, Yu An, Xin Wang, Yan Pan, Yilixiati Xiaokaiti, Jianhui Duan, Xin Li, Lu Tie, Min Ye, Xuejun Li
Pancreatic cancer is a highly aggressive malignancy, which is intrinsically resistant to current chemotherapies. Herein, we investigate whether bisdemethoxycurcumin (BDMC), a derivative of curcumin, potentiates gemcitabine in human pancreatic cancer cells. The result suggests that BDMC sensitizes gemcitabine by inducing mitochondrial dysfunctions and apoptosis in PANC-1 and MiaPaCa-2 pancreatic cancer cells. Utilizing two-dimensional gel electrophoresis and mass spectrometry, we identify 13 essential proteins with significantly altered expressions in response to gemcitabine alone or combined with BDMC...
November 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27825319/growth-hormone-is-increased-in-the-lungs-and-enhances-experimental-lung-metastasis-of-melanoma-in-dj-1-ko-mice
#4
Chia-Hung Chien, Ming-Jen Lee, Houng-Chi Liou, Horng-Huei Liou, Wen-Mei Fu
BACKGROUND: Growth hormone (GH) mainly serves an endocrine function to regulate somatic growth, but also serves an autocrine function in lung growth and pulmonary function. Several recent studies have demonstrated the role of autocrine GH in tumor progression in some organs. However, it is not clear whether excessive secretion of GH in the lungs is related to pulmonary nodule formation. METHODS: Firstly, the lung tissues dissected from mice were used for Western blotting and PCR measurement...
November 8, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27818604/tat-dj-1-inhibits-oxidative-stress-mediated-rinm5f-cell-death-through-suppression-of-nf-%C3%AE%C2%BAb-and-mapk-activation
#5
Hyo Sang Jo, Hyun Ju Cha, Sang Jin Kim, Hyeon Ji Yeo, Su Bin Cho, Jung Hwan Park, Chi Hern Lee, Eun Ji Yeo, Yeon Joo Choi, Won Sik Eum, Soo Young Choi
Oxidative stress is highly involved in the development of diabetes mellitus by destruction of pancreatic β-cells. DJ-1 is an antioxidant protein and DJ-1 expression levels are known to be reduced in diabetes mellitus. Thus, we examined the effects of DJ-1 protein against oxidative stress-induced pancreatic β-cell (RINm5F) death using cell permeable wild-type and mutant-type (C106A) Tat-DJ-1 proteins, which both efficiently transduced into RINm5F cells. Intracellular stability of wild-type Tat-DJ-1 persisted two times longer than C106A Tat-DJ-1...
2016: Medicinal Chemistry Research
https://www.readbyqxmd.com/read/27818248/genetics-of-parkinson-s-disease
#6
REVIEW
Christina M Lill
Almost two decades after the identification of SNCA as the first causative gene in Parkinson's disease (PD) and the subsequent understanding that genetic factors play a substantial role in PD development, our knowledge of the genetic architecture underlying this disease has vastly improved. Approximately 5-10% of patients suffer from a monogenic form of PD where autosomal dominant mutations in SNCA, LRRK2, and VPS35 and autosomal recessive mutations in PINK1, DJ-1, and Parkin cause the disease with high penetrance...
December 2016: Molecular and Cellular Probes
https://www.readbyqxmd.com/read/27802241/modulation-of-parkinson-s-disease-associated-protein-rescues-alzheimer-s-disease-degeneration
#7
Akihiko Nunomura, Xiongwei Zhu, George Perry
DJ-1, a causative gene product of an autosomal recessive familial form of Parkinson's disease (PD), plays roles in reducing oxidative stress and transcriptional regulation. Loss of its function is thought to result in the onset of PD. DJ-1 has been demonstrated to show general cytoprotective function mainly through antioxidant properties and possibly regulates the extent of stroke-induced damage and neurodegeneration in Alzheimer's disease (AD). The paper, "Effects of a DJ-1-Binding Compound on Spatial Learning and Memory Impairment in a Mouse Model of Alzheimer's Disease", by Kitamura et al...
October 12, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27769868/oxidative-stress-a-major-pathogenesis-and-potential-therapeutic-target-of-antioxidative-agents-in-parkinson-s-disease-and-alzheimer-s-disease
#8
REVIEW
Tianfang Jiang, Qian Sun, Shengdi Chen
Oxidative stress reflects an imbalance between the overproduction and incorporation of free radicals and the dynamic ability of a biosystem to detoxify reactive intermediates. Free radicals produced by oxidative stress are one of the common features in several experimental models of diseases. Free radicals affect both the structure and function of neural cells, and contribute to a wide range of neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Although the precise mechanisms that result in the degeneration of neurons and the relevant pathological changes remain unclear, the crucial role of oxidative stress in the pathogenesis of neurodegenerative diseases is associated with several proteins (such as α-synuclein, DJ-1, Amyloid β and tau protein) and some signaling pathways (such as extracellular regulated protein kinases, phosphoinositide 3-kinase/Protein Kinase B pathway and extracellular signal-regulated kinases 1/2) that are tightly associated with the neural damage...
December 2016: Progress in Neurobiology
https://www.readbyqxmd.com/read/27766037/deficiency-of-dj-1-ameliorates-liver-fibrosis-through-inhibition-of-hepatic-ros-production-and-inflammation
#9
Yingxue Yu, Xuehua Sun, Jinyang Gu, Chang Yu, Yankai Wen, Yueqiu Gao, Qiang Xia, Xiaoni Kong
Liver fibrosis is a global health problem and previous studies have demonstrated that reactive oxygen species (ROS) play important roles in fibrogenesis. Parkinson disease (autosomal recessive, early onset) 7 (Park7) also called DJ-1 has an essential role in modulating cellular ROS levels. DJ-1 therefore may play functions in liver fibrogenesis and modulation of DJ-1 may be a promising therapeutic approach. Here, wild-type (WT) and DJ-1 knockout (DJ-1 KO) mice were administrated with carbon tetrachloride (CCl4) to induce liver fibrosis or acute liver injury...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/27763504/neuroprotective-effect-of-the-marine-derived-compound-11-dehydrosinulariolide-through-dj-1-related-pathway-in-in-vitro-and-in-vivo-models-of-parkinson-s-disease
#10
Chien-Wei Feng, Han-Chun Hung, Shi-Ying Huang, Chun-Hong Chen, Yun-Ru Chen, Chun-Yu Chen, San-Nan Yang, Hui-Min David Wang, Ping-Jyun Sung, Jyh-Horng Sheu, Kuan-Hao Tsui, Wu-Fu Chen, Zhi-Hong Wen
Parkinson's disease (PD) is a neurodegenerative disorder characterized by tremor, rigidity, bradykinesia, and gait impairment. In a previous study, we found that the marine-derived compound 11-dehydrosinulariolide (11-de) upregulates the Akt/PI3K pathway to protect cells against 6-hydroxydopamine (6-OHDA)-mediated damage. In the present study, SH-SY5Y, zebrafish and rats were used to examine the therapeutic effect of 11-de. The results revealed the mechanism by which 11-de exerts its therapeutic effect: the compound increases cytosolic or mitochondrial DJ-1 expression, and then activates the downstream Akt/PI3K, p-CREB, and Nrf2/HO-1 pathways...
October 17, 2016: Marine Drugs
https://www.readbyqxmd.com/read/27761515/swath-ms-proteome-profiling-data-comparison-of-dj-1-parkin-and-pink1-knockout-rat-striatal-mitochondria
#11
Kelly L Stauch, Lance M Villeneuve, Phillip R Purnell, Sanjit Pandey, Chittibabu Guda, Howard S Fox
This article reports changes in the striatal non-synaptic mitochondrial proteome of DJ-1, Parkin, and PINK1 knockout (KO) rats at 3 months of age. DJ-1, Parkin, and PINK1 mutations cause autosomal-recessive parkinsonism. It is thought that loss of function of these proteins contributes to the onset and pathogenesis of Parkinson׳s disease (PD). As DJ-1, Parkin, and PINK1 have functions in the regulation of mitochondria, the dataset generated here highlights protein expression changes, which can be helpful for understanding pathological mitochondrial alterations...
December 2016: Data in Brief
https://www.readbyqxmd.com/read/27748821/subcellular-localization-of-dj-1-in-human-hl-60-leukemia-cells-in-response-to-diallyl-disulfide-treatment
#12
Qingye Li, Yuxian Tang, Jing Qin, Lan Yi, Yening Yang, Juan Wang, Jie He, Qi Su, Hui Tan
Diallyl disulfide (DADS) has been demonstrated to exert potent anticancer effects in vitro and in vivo. Previous studies indicate that DADS may induce the differentiation and/or apoptosis of human leukemia cells in vitro. However, the mechanisms underlying these anticancer effects remain elusive. The aim of the present study was to investigate alterations in the subcellular localization of protein deglycase DJ‑1 (also known as Parkinsonism associated deglycase-7, PARK-7) in the cytoplasm, nucleus and mitochondria of human leukemia HL‑60 cells induced by DADS, in order to provide novel experimental evidence for the molecular mechanisms underlying the anticancer mechanisms of DADS in leukemia cells...
November 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27735193/dj-1-park7-impairs-bacterial-clearance-in-sepsis
#13
Hajera Amatullah, Yuexin Shan, Brittany L Beauchamp, Patricia L Gali, Sahil Gupta, Tatiana Maron-Gutierrez, Edwin R Speck, Alison E Fox-Robichaud, Jennifer L Y Tsang, Shirley H J Mei, Tak W Mak, Patricia Rm Rocco, John W Semple, Haibo Zhang, Pingzhao Hu, John C Marshall, Duncan J Stewart, Mary-Ellen Harper, Patricia C Liaw, W Conrad Liles, Claudia C Dos Santos
RATIONALE & OBJECTIVES: Effective and rapid bacterial clearance is a fundamental determinant of outcome(s) in sepsis. DJ-1 is a well-established reactive oxygen species (ROS) scavenger. As cellular ROS status is pivotal to inflammation and bacterial killing, we determined the role of DJ-1 in bacterial sepsis. METHODS: We used cell and murine models with gain and loss of function experiments, plasma and cells from septic patients. MEASUREMENTS & RESULTS: Stimulation of bone marrow derived macrophages (BMM) with endotoxin resulted in increased DJ-1 mRNA and protein expression...
October 13, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27734217/targeted-knockdown-of-dj-1-induces-multiple-myeloma-cell-death-via-klf6-upregulation
#14
Prahlad V Raninga, Giovanna Di Trapani, Slavica Vuckovic, Kathryn F Tonissen
Multiple myeloma (MM) is an incurable plasma B cell malignancy. Despite recent advancements in anti-MM therapies, development of drug resistance remains a major clinical hurdle. DJ-1, a Parkinson's disease-associated protein, is upregulated in many cancers and its knockdown suppresses tumor growth and overcomes chemoresistance. However, the role of DJ-1 in MM remains unknown. Using gene expression databases we found increased DJ-1 expression in MM patient cells, which correlated with shorter overall survival and poor prognosis in MM patients...
December 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27717584/parkinson-s-disease-snca-park2-and-lrrk2-targeting-micrornas-elevated-in-cingulate-gyrus
#15
Roman Tatura, Theo Kraus, Armin Giese, Thomas Arzberger, Malte Buchholz, Günter Höglinger, Ulrich Müller
INTRODUCTION: In order to better understand the role of epigenetic influences in the etiology of Parkinson's disease (PD), we studied the expression of microRNAs in gyri cinguli of patients and controls. METHODS: Expression profiling of 744 well-characterized microRNAs in gyri cinguli from patients and controls using TaqMan array microRNA cards. Verification of significantly dysregulated microRNAs by SYBR Green qRT-PCR. RESULTS: First screen by TaqMan array identified 43 microRNAs that were upregulated in gyri cinguli from patients...
September 28, 2016: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/27703196/degradation-of-redox-sensitive-proteins-including-peroxiredoxins-and-dj-1-is-promoted-by-oxidation-induced-conformational-changes-and-ubiquitination
#16
In-Kang Song, Jae-Jin Lee, Jin-Hwan Cho, Jihye Jeong, Dong-Hae Shin, Kong-Joo Lee
Reactive oxygen species (ROS) are key molecules regulating various cellular processes. However, what the cellular targets of ROS are and how their functions are regulated is unclear. This study explored the cellular proteomic changes in response to oxidative stress using H2O2 in dose- and recovery time-dependent ways. We found discernible changes in 76 proteins appearing as 103 spots on 2D-PAGE. Of these, Prxs, DJ-1, UCH-L3 and Rla0 are readily oxidized in response to mild H2O2 stress, and then degraded and active proteins are newly synthesized during recovery...
October 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27690738/the-small-heat-shock-protein-hsp31-cooperates-with-hsp104-to-modulate-sup35-prion-aggregation
#17
Kiran Aslam, Chai-Jui Tsai, Tony R Hazbun
The yeast homolog of DJ-1, Hsp31, is a multifunctional protein that is involved in several cellular pathways including detoxification of the toxic metabolite methylglyoxal and as a protein deglycase. Prior studies ascribed Hsp31 as a molecular chaperone that can inhibit α-Syn aggregation in vitro and alleviate its toxicity in vivo. It was also shown that Hsp31 inhibits Sup35 aggregate formation in yeast, however, it is unknown if Hsp31 can modulate [PSI(+)] phenotype and Sup35 prionogenesis. Other small heat shock proteins, Hsp26 and Hsp42 are known to be a part of a synergistic proteostasis network that inhibits Sup35 prion formation and promotes its disaggregation...
October 3, 2016: Prion
https://www.readbyqxmd.com/read/27662308/effects-of-a-dj-1-binding-compound-on-spatial-learning-and-memory-impairment-in-a-mouse-model-of-alzheimer-s-disease
#18
Yoshihisa Kitamura, Masatoshi Inden, Yasuto Kimoto, Kazuyuki Takata, Daijiro Yanagisawa, Masanori Hijioka, Eishi Ashihara, Ikuo Tooyama, Shun Shimohama, Hiroyoshi Ariga
Previously, DJ-1 modulator UCP0054278/comp-B was identified by virtual screening, where comp-B interacts with DJ-1 to produce antioxidant and neuroprotective responses in Parkinson's disease models. However, the effect of comp-B in an in vivo Alzheimer's disease (AD) model is yet undetermined. Thus, we examined the effect of comp-B on spatial learning, memory, and amyloid-β (Aβ) clearance in a transgenic mouse model of AD. We found that comp-B resolved the cognitive deficits, reduced insoluble Aβ42 levels, and prevented the degeneration of synaptic functions, thereby suggesting that comp-B may become a major compound for AD treatment...
September 21, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27629121/alterations-in-the-proliferative-apoptotic-equilibrium-in-semen-of-adolescents-with-varicocele
#19
Larissa Berloffa Belardin, Paula Toni Del Giudice, Mariana Camargo, Paula Intasqui, Mariana Pereira Antoniassi, Ricardo Pimenta Bertolla, Agnaldo Pereira Cedenho
PURPOSE: To verify if the presence of varicocele (grades II and III) with and without seminal alterations, using the 5(th) centile cutoff values in table A1.1 of the World Health Organization (WHO, 2010) manual, alters the seminal plasma levels of proteins DNASE1 (deoxyribonuclease-1) and IGFBP7 (Insulin-like growth factor-binding protein 7), which are related to apoptosis regulation and cell proliferation, respectively, demonstrating that these proteins are important for correct spermatogenesis...
September 14, 2016: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/27619486/a-novel-tyrosine-hydroxylase-variant-in-a-group-of-chinese-patients-with-dopa-responsive-dystonia
#20
Ya-Ping Yan, Bo Zhang, Yan-Fang Mao, Zhang-Yu Guo, Jun Tian, Guo-Hua Zhao, Jia-Li Pu, Wei Luo, Zhi-Yuan Ouyang, Bao-Rong Zhang
Dopa-responsive dystonia (DRD) comprises a heterogeneous group of movement disorders. A limited number of studies of Chinese patients with DRD have been reported. In the present study, we investigated the clinical and genetic features of 12 Chinese DRD families. Point mutation analysis of the GTP-cyclohydrolase I (GCH1), tyrosine hydroxylase (TH) and sepiapterin reductase (SPR) genes was conducted by direct sequencing. In addition, multiplex ligation-dependent probe amplification targeting GCH1 and TH was performed in "mutation-free" patients...
October 5, 2016: International Journal of Neuroscience
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