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https://www.readbyqxmd.com/read/28237703/effect-of-cellular-ubiquitin-levels-on-the-regulation-of-oxidative-stress-response-and-proteasome-function-via-nrf1
#1
Donghee Lee, Kwon-Yul Ryu
The polyubiquitin genes Ubb and Ubc are upregulated under oxidative stress induced by arsenite [As(III)]. However, the role of ubiquitin (Ub) under As(III) exposure is not known in detail. In a previous study, we showed that the reduced viability observed in Ubc(-/-) mouse embryonic fibroblasts under As(III) exposure was not due to dysregulation of the Nrf2-Keap1 pathway, which prompted us to investigate another NFE2 family protein, nuclear factor erythroid 2-related factor 1 (Nrf1). In this study, we found that Ub deficiency due to Ubc knockdown in N2a cells reduced cell viability and proteasome activity under As(III) exposure...
February 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28220896/mitochondrial-dysregulation-secondary-to-endoplasmic-reticulum-stress-in-autosomal-dominant-tubulointerstitial-kidney-disease-umod-adtkd-umod
#2
Elisabeth Kemter, Thomas Fröhlich, Georg J Arnold, Eckhard Wolf, Rüdiger Wanke
'Autosomal dominant tubulointerstitial kidney disease - UMOD' (ADTKD-UMOD) is caused by impaired maturation and secretion of mutant uromodulin (UMOD) in thick ascending limb of Henle loop (TAL) cells, resulting in endoplasmic reticulum (ER) stress and unfolded protein response (UPR). To gain insight into pathophysiology, we analysed proteome profiles of TAL-enriched outer renal medulla samples from ADTKD-UMOD and control mice by quantitative LC-MS/MS. In total, 212 differentially abundant proteins were identified...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28178868/low-level-lasers-effect-on-proliferation-migration-and-anti-apoptosis-of-mesenchymal-stem-cells
#3
Kan Yin, Rongjia Zhu, Shihua Wang, Robert Chunhua Zhao
Mesenchymal stem cells (MSCs) have been found to be helpful elements in tissue regeneration. Photobiomodulation (PBM) used extremely low level lasers (LLL) to affect the behaviour of cells. The effect mechanism of LLL on MSCs remained to be discovered. Here cell viability was assessed using MTS assays and cell cycle was evaluated by FACS. The influence of LLL on mitochondrial biogenesis (fission or fusion) and function (ATP, ROS, NO) were evaluated by TEM, FACS, RT-PCR, immunocytochemistry. Cell migration and cytoskeleton alteration (actin and tubulin) were evaluated using transwell assay, immunocytochemistry, ELISA and Western blotting...
February 8, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28177717/a-systematic-upregulation-of-nuclear-and-mitochondrial-genes-is-not-present-in-the-initial-post-exercise-recovery-period-in-human-skeletal-muscle
#4
Trisha D Scribbans, Brittany A Edgett, Jacob T Bonafiglia, Brittany L Baechler, Joe Quadrilatero, Brendon J Gurd
The purpose of the current investigation was to determine if an exercise-mediated upregulation of nuclear and mitochondrial-encoded genes targeted by the transcriptional co-activator peroxisome-proliferator-activated receptor gamma co-activator-1 alpha (PGC-1α) occurs in a systematic manner following different exercise intensities in humans. Ten recreationally active males (Age: 23 ±3 yrs; VO2peak: 41.8 ±6.6 mL/kg/min) completed two acute bouts of work-matched interval exercise at ~73% (LO) and ~100% (HI) of work rate at VO2peak in a randomized cross-over design...
January 17, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28152064/nrf2-regulates-mass-accrual-and-the-antioxidant-endogenous-response-in-bone-differently-depending-on-the-sex-and-age
#5
Gretel Gisela Pellegrini, Meloney Cregor, Kevin McAndrews, Cynthya Carolina Morales, Linda Doyle McCabe, George P McCabe, Munro Peacock, David Burr, Connie Weaver, Teresita Bellido
Accumulation of reactive oxygen species (ROS) is an important pathogenic mechanism underling the loss of bone mass and strength with aging and other conditions leading to osteoporosis. The transcription factor erythroid 2-related factor2 (Nrf2) plays a central role in activating the cellular response to ROS. Here, we examined the endogenous response of bone regulated by Nrf2, and its relationship with bone mass and architecture in the male and female murine skeleton. Young (3 month-old) and old (15 month-old) Nrf2 knockout (KO) mice of either sex exhibited the expected reduction in Nrf2 mRNA expression compared to wild type (WT) littermates...
2017: PloS One
https://www.readbyqxmd.com/read/28146428/hypoxia-reduces-testosterone-synthesis-in-mouse-leydig-cells-by-inhibiting-nrf1-activated-star-expression
#6
Xueting Wang, Longlu Pan, Zhiran Zou, Dan Wang, Yapeng Lu, Zhangji Dong, Li Zhu
Male fertility disorders play a key role in half of all infertility cases. Reduction in testosterone induced by hypoxia might cause diseases in reproductive system and other organs. Hypoxic exposure caused a significant decrease of NRF1. Software analysis reported that the promoter region of steroidogenic acute regulatory protein (StAR) contained NRF1 binding sites, indicating NRF1 promoted testicular steroidogenesis. The purpose of this study is to determine NRF1 is involved in testosterone synthesis; and under hypoxia, the decrease of testosterone synthesis is caused by lower expression of NRF1...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28132893/inhibition-of-the-proteasome-%C3%AE-2-site-sensitizes-triple-negative-breast-cancer-cells-to-%C3%AE-5-inhibitors-and-suppresses-nrf1-activation
#7
Emily S Weyburne, Owen M Wilkins, Zhe Sha, David A Williams, Alexandre A Pletnev, Gerjan de Bruin, Hermann S Overkleeft, Alfred L Goldberg, Michael D Cole, Alexei F Kisselev
The proteasome inhibitors carfilzomib (Cfz) and bortezomib (Btz) are used successfully to treat multiple myeloma, but have not shown clinical efficacy in solid tumors. Here we show that clinically achievable inhibition of the β5 site of the proteasome by Cfz and Btz does not result in loss of viability of triple-negative breast cancer cell lines. We use site-specific inhibitors and CRISPR-mediated genetic inactivation of β1 and β2 to demonstrate that inhibiting a second site of the proteasome, particularly the β2 site, sensitizes cell lines to Btz and Cfz in vitro and in vivo...
January 25, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28120943/melatonin-ameliorates-myocardial-ischemia-reperfusion-injury-in-type-1-diabetic-rats-by-preserving-mitochondrial-function-role-of-ampk-pgc-1%C3%AE-sirt3-signaling
#8
Liming Yu, Bing Gong, Weixun Duan, Chongxi Fan, Jian Zhang, Zhi Li, Xiaodong Xue, Yinli Xu, Dandan Meng, Buying Li, Meng Zhang, Bin Zhang, Zhenxiao Jin, Shiqiang Yu, Yang Yang, Huishan Wang
Enhancing mitochondrial biogenesis and reducing mitochondrial oxidative stress have emerged as crucial therapeutic strategies to ameliorate diabetic myocardial ischemia/reperfusion (MI/R) injury. Melatonin has been reported to be a safe and potent cardioprotective agent. However, its role on mitochondrial biogenesis or reactive oxygen species (ROS) production in type 1 diabetic myocardium and the underlying mechanisms remain unknown. We hypothesize that melatonin ameliorates MI/R injury in type 1 diabetic rats by preserving mitochondrial function via AMPK-PGC-1α-SIRT3 signaling pathway...
January 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28118753/protective-effects-of-leucine-on-redox-status-and-mitochondrial-related-gene-abundance-in-the-jejunum-of-intrauterine-growth-retarded-piglets-during-early-weaning-period
#9
Qiang Huang, Wen Xu, Kai-Wen Bai, Jin-Tian He, Hussain Ahmad, Le Zhou, Li-Li Zhang, Tian Wang
The aim of this study was to investigate the effects of dietary supplementation with 0.35% l-leucine on redox status and gene abundance relating to mitochondrial biogenesis and function in the jejunum of intrauterine growth-retarded (IUGR) piglets during early weaning period. According to a 2 × 2 factorial arrangement, 16 IUGR and 16 normal body weight (NBW) piglets were fed a basal diet without l-leucine supplementation or a basal diet plus 0.35% l-leucine supplementation from the age of 14 to 35 d. The results showed that compared with NBW piglets, IUGR piglets had a lower (p < 0...
January 24, 2017: Archives of Animal Nutrition
https://www.readbyqxmd.com/read/28116391/a-rich-medium-chain-triacylglycerol-diet-benefits-adiposity-but-has-adverse-effects-on-the-markers-of-hepatic-lipogenesis-and-beta-oxidation
#10
Carolina Maria de Oliveira Chamma, Thereza Cristina Lonzetti Bargut, Carlos Alberto Mandarim-de-Lacerda, Marcia Barbosa Aguila
We investigated the increasing amounts of medium-chain triacylglycerol (MCT) in the diet on hepatic lipid metabolism. Mature C57BL/6 male mice were randomly divided into five groups (n = 10/group). The animals received their diet for 12 weeks, as a control (C group, 10% of energy from lipids); high-fat lard (HF group, isoenergetic diet, 50% of energy from lipids with lard); a mixture of lard and MCT oil (with a gradual replacement of lard by MCT: HF-MCT25%, HF-MCT75%, and HF-MCT100% groups). At euthanasia, we collected blood and dissected the liver for analyses (glucose, insulin, HOMA-IR, QUICK index, and triacylglycerol, light microscopy, western blotting, and RT-qPCR)...
January 24, 2017: Food & Function
https://www.readbyqxmd.com/read/28094792/identification-of-a-nuclear-respiratory-factor-1-recognition-motif-in-the-apolipoprotein-e-variant-apoe4-linked-to-alzheimer-s-disease
#11
Anne Urfer-Buchwalder, Roman Urfer
Alzheimer's disease affects tens of millions of people worldwide and its prevalence continues to rise. It is caused by a combination of a subject's heredity, environment, lifestyle, and medical condition. The most significant genetic risk factor for late onset Alzheimer's disease is a variant of the apolipoprotein E gene, APOE4. Here we show that the single nucleotide polymorphism rs429358 that defines APOE4 is located in a short sequence motif repeated several times within exon 4 of apolipoprotein E, reminiscent of the structure of transcriptional enhancers...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28088524/possible-roles-of-the-transcription-factor-nrf1-nfe2l1-in-neural-homeostasis-by-regulating-the-gene-expression-of-deubiquitinating-enzymes
#12
Hiroaki Taniguchi, Shota Okamuro, Misaki Koji, Tsuyoshi Waku, Kaori Kubo, Atsushi Hatanaka, Yimeng Sun, A M Masudul Azad Chowdhury, Akiyoshi Fukamizu, Akira Kobayashi
The transcription factor Nrf1 (NFE2L1) maintains protein homeostasis (proteostasis) by regulating the gene expression of proteasome subunits in response to proteasome inhibition. The deletion of the Nrf1 gene in neural stem/progenitor cells causes severe neurodegeneration due to the accumulation of ubiquitinated proteins in Purkinje cells and motor neurons (Nrf1 NKO mice). However, the molecular mechanisms governing this neurodegenerative process remain unclear. We demonstrate herein that the loss of Nrf1 leads to the reduced gene expression of the deubiquitinating enzymes (DUBs) but not proteasome subunits in Nrf1 NKO mice between P7 and P18...
January 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28078253/effects-of-eicosapentaenoic-acid-and-docosahexaenoic-acid-on-mitochondrial-dna-replication-and-pgc-1%C3%AE-gene-expression-in-c2c12-muscle-cells
#13
Mak-Soon Lee, Yoonjin Shin, Sohee Moon, Seunghae Kim, Yangha Kim
Mitochondrial biogenesis is a complex process requiring coordinated expression of nuclear and mitochondrial genomes. The peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α) is a key regulator of mitochondrial biogenesis, and it controls mitochondrial DNA (mtDNA) replication within diverse tissues, including muscle tissue. The aim of this study was to investigate the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on mtDNA copy number and PGC-1α promoter activity in C2C12 muscle cells...
December 2016: Preventive Nutrition and Food Science
https://www.readbyqxmd.com/read/28068899/maternal-bmi-as-a-predictor-of-methylation-of-obesity-related-genes-in-saliva-samples-from-preschool-age-hispanic-children-at-risk-for-obesity
#14
Kathryn Tully Oelsner, Yan Guo, Sophie Bao-Chieu To, Amy L Non, Shari L Barkin
BACKGROUND: The study of epigenetic processes and mechanisms present a dynamic approach to assess complex individual variation in obesity susceptibility. However, few studies have examined epigenetic patterns in preschool-age children at-risk for obesity despite the relevance of this developmental stage to trajectories of weight gain. We hypothesized that salivary DNA methylation patterns of key obesogenic genes in Hispanic children would 1) correlate with maternal BMI and 2) allow for identification of pathways associated with children at-risk for obesity...
January 9, 2017: BMC Genomics
https://www.readbyqxmd.com/read/27993529/sulforaphane-induces-differential-modulation-of-mitochondrial-biogenesis-and-dynamics-in-normal-cells-and-tumor-cells
#15
Mario Negrette-Guzmán, Sara Huerta-Yepez, Mario I Vega, Juan Carlos León-Contreras, Rogelio Hernández-Pando, Omar Noel Medina-Campos, Esteban Rodríguez, Edilia Tapia, José Pedraza-Chaverri
Antioxidant-based chemotherapy has been intensely debated. Herein, we show that sulforaphane (SFN) induced mitochondrial biogenesis followed by mitochondrial fusion in a kidney cell line commonly used in nephroprotective models. At the same concentration and exposure time, SFN induced cell death in prostate cancer cells accompanied by mitochondrial biogenesis and fragmentation. Stabilization of the nuclear factor E2-related factor-2 (Nrf2) could be associated with these effects in the tumor cell line. An increase in the peroxisome proliferator-activated receptor-γ co-activator-1α (PGC1α) level and a decrease in the hypoxia-inducible factor-1α (HIF1α) level would suggest a possible metabolic shift...
February 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/27983596/estrogenic-endocrine-disrupting-chemicals-influencing-nrf1-regulated-gene-networks-in-the-development-of-complex-human-brain-diseases
#16
REVIEW
Mark Preciados, Changwon Yoo, Deodutta Roy
During the development of an individual from a single cell to prenatal stages to adolescence to adulthood and through the complete life span, humans are exposed to countless environmental and stochastic factors, including estrogenic endocrine disrupting chemicals. Brain cells and neural circuits are likely to be influenced by estrogenic endocrine disruptors (EEDs) because they strongly dependent on estrogens. In this review, we discuss both environmental, epidemiological, and experimental evidence on brain health with exposure to oral contraceptives, hormonal therapy, and EEDs such as bisphenol-A (BPA), polychlorinated biphenyls (PCBs), phthalates, and metalloestrogens, such as, arsenic, cadmium, and manganese...
December 13, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27923775/the-plasticizer-bbp-selectively-inhibits-epigenetic-regulator-sirtuin-during-differentiation-of-c3h10t1-2-stem-cell-line
#17
Jian Zhang, Mahua Choudhury
Exposure to environmental chemicals can perturb an individual's metabolic set point, especially during critical periods of development, and as a result increase his or her propensity towards obesity that is manifested later in life and possibly in successive generations. We hypothesized that benzyl butyl phthalate (BBP), a widespread endocrine disruptor, may impair one important epigenetic regulator, sirtuin, in mesenchymal stem cells and induce adipogenesis. Our results showed that gene expression of two well-known adipogenic markers, aP2 and PPARγ, were significantly increased from day 2 to day 8 under 50μM BBP exposure when compared to control in C3H10T1/2 stem cells (p<0...
March 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27920251/a-homeostatic-shift-facilitates-endoplasmic-reticulum-proteostasis-through-transcriptional-integration-of-proteostatic-stress-response-pathways
#18
Liam Baird, Tadayuki Tsujita, Eri H Kobayashi, Ryo Funayama, Takeshi Nagashima, Keiko Nakayama, Masayuki Yamamoto
Eukaryotic cells maintain protein homeostasis through the activity of multiple basal and inducible systems, which function in concert to allow cells to adapt to a wide range of environmental conditions. Although the transcriptional programs regulating individual pathways have been studied in detail, it is not known how the different pathways are transcriptionally integrated such that a deficiency in one pathway can be compensated by a change in an auxiliary response. One such pathway that plays an essential role in many proteostasis responses is the ubiquitin-proteasome system, which functions to degrade damaged, unfolded, or short half-life proteins...
February 15, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27917127/maternal-high-fat-diet-alters-skeletal-muscle-mitochondrial-catalytic-activity-in-adult-male-rat-offspring
#19
Chantal A Pileggi, Christopher P Hedges, Stephanie A Segovia, James F Markworth, Brenan R Durainayagam, Clint Gray, Xiaoyuan D Zhang, Matthew P G Barnett, Mark H Vickers, Anthony J R Hickey, Clare M Reynolds, David Cameron-Smith
A maternal high-fat (HF) diet during pregnancy can lead to metabolic compromise, such as insulin resistance in adult offspring. Skeletal muscle mitochondrial dysfunction is one mechanism contributing to metabolic impairments in insulin resistant states. Therefore, the present study aimed to investigate whether mitochondrial dysfunction is evident in metabolically compromised offspring born to HF-fed dams. Sprague-Dawley dams were randomly assigned to receive a purified control diet (CD; 10% kcal from fat) or a high fat diet (HFD; 45% kcal from fat) for 10 days prior to mating, throughout pregnancy and during lactation...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27907152/dietary-probiotic-bacillus-subtilis-strain-fmbj-increases-antioxidant-capacity-and-oxidative-stability-of-chicken-breast-meat-during-storage
#20
Wen Kai Bai, Fei Jing Zhang, Tian Jin He, Peng Wei Su, Xiong Zhi Ying, Li Li Zhang, Tian Wang
This study was aimed to measure the dietary effects of probiotic Bacillus subtilis strain fmbj (BS fmbj) on antioxidant capacity and oxidative stability of chicken breast meat during storage. Treatment groups were fed the basal diet with BS fmbj at 0 g/kg (CON), 0.2 g/kg (BS-1), 0.3 g/kg (BS-2), or 0.4 g/kg (BS-3) doses without antibiotics. During 8 days of storage at 4°C, BS-2 group showed a significant improvement (P < 0.05) on meat quality (pH, Drip loss, Cooking loss, Shear force, color L*, a*, b*), free radical scavenging activity (DPPH, ABTS+, H2O2), tissues antioxidant enzyme capacity (SOD, CAT, GSH-Px, GSH, T-SH), mitochondria antioxidant enzyme capacity (MnSOD, GPx, GSH), mRNA expression of antioxidant genes (Nrf2, HO-1, SOD, CAT, GSH-Px) and mitochondrial function genes (avUCP, NRF1, NRF2, TFAM, PGC-1α), oxidative damage index (MDA, ROS, PC, 8-OHdG), and MMP level in chicken breast meat as compared to the CON group...
2016: PloS One
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