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https://www.readbyqxmd.com/read/29149604/nrf1-is-an-er-membrane-sensor-that-is-central-to-cholesterol-homeostasis
#1
Scott B Widenmaier, Nicole A Snyder, Truc B Nguyen, Alessandro Arduini, Grace Y Lee, Ana Paula Arruda, Jani Saksi, Alexander Bartelt, Gökhan S Hotamisligil
Cholesterol is a critical nutrient requiring tight constraint in the endoplasmic reticulum (ER) due to its uniquely challenging biophysical properties. While the mechanisms by which the ER defends against cholesterol insufficiency are well described, it remains unclear how the ER senses and effectively defends against cholesterol excess. Here, we identify the ER-bound transcription factor nuclear factor erythroid 2 related factor-1, Nrf1/Nfe2L1, as a critical mediator of this process. We show that Nrf1 directly binds to and specifically senses cholesterol in the ER through a defined domain and that cholesterol regulates Nrf1 turnover, processing, localization, and activity...
November 16, 2017: Cell
https://www.readbyqxmd.com/read/29128369/inhibition-of-poly-adp-ribose-polymerase-1-alters-expression-of-mitochondria-related-genes-in-pc12-cells-relevance-to-mitochondrial-homeostasis-in-neurodegenerative-disorders
#2
Grzegorz A Czapski, Magdalena Cieślik, Przemysław L Wencel, Sylwia Wójtowicz, Robert P Strosznajder, Joanna B Strosznajder
Alzheimer's disease (AD) is characterized by the release of amyloid beta peptides (Aβ) in the form of monomers/oligomers which may lead to oxidative stress, mitochondria dysfunction, synaptic loss, neuroinflammation and, in consequence, to overactivation of poly(ADP-ribose) polymerase-1 (PARP-1). However, Aβ peptides are also released in the brain ischemia, traumatic injury and in inflammatory response. PARP-1 is suggested to be a promising target in therapy of neurodegenerative disorders. We investigated the impact of PARP-1 inhibition on transcription of mitochondria-related genes in PC12 cells...
November 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29125827/early-cerebellar-deficits-in-mitochondrial-biogenesis-and-respiratory-chain-complexes-in-the-kiko-mouse-model-of-friedreich-ataxia
#3
Hong Lin, Jordi Magrane, Amy Rattelle, Anna Stepanova, Alexander Galkin, Elisia M Clark, Yi Na Dong, Sarah M Halawani, David R Lynch
Friedreich ataxia (FRDA), the most common recessive inherited ataxia, results from deficiency of frataxin, a small mitochondrial protein crucial for iron-sulphur cluster formation and ATP production. Frataxin deficiency is associated with mitochondrial dysfunction in FRDA patients and animal models; however, early mitochondrial pathology in FRDA cerebellum remains elusive. Using frataxin knock-in/knockout (KIKO) mice and KIKO mice carrying the mitoDendra transgene, we show early cerebellar deficits in mitochondrial biogenesis and respiratory chain complexes in this FRDA model...
November 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29123480/impairment-of-mitochondrial-biogenesis-and-dynamics-involved-in-isoniazid-induced-apoptosis-of-hepg2-cells-was-alleviated-by-p38-mapk-pathway
#4
Tianguang Zhang, Takashi Ikejima, Lizhong Li, Ruiqin Wu, Xiaoyan Yuan, Jun Zhao, Yimei Wang, Shuangqing Peng
Isoniazid (INH), a widely used first-line antitubercular drug, has been noted to be associated with hepatotoxicity. In spite of extensive researches over many decades, the mechanism of INH-induced hepatotoxicity still remains poorly understood. Recently, mitochondrial toxicity has been emerging as a new paradigm for INH-induced hepatotoxicity. In this study, we showed that INH impaired mitochondrial biogenesis and dynamics in human hepatocarcinoma HepG2 cells. INH reduced mitochondrial membrane potential (MMP) and induced mitochondria swelling...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29076578/impairment-of-protein-degradation-and-proteasome-function-in-hereditary-neuropathies
#5
Jordan J S VerPlank, Sudarsanareddy Lokireddy, M Laura Feltri, Alfred L Goldberg, Lawrence Wrabetz
In several neurodegenerative diseases in which misfolded proteins accumulate there is impairment of the ubiquitin proteasome system (UPS). We tested if a similar disruption of proteostasis occurs in hereditary peripheral neuropathies. In sciatic nerves from mouse models of two human neuropathies, Myelin Protein Zero mutation (S63del) and increased copy number (P0 overexpression), polyubiquitinated proteins accumulated, and the overall rates of protein degradation were decreased. 26S proteasomes affinity-purified from sciatic nerves of S63del mice were defective in degradation of peptides and a ubiquitinated protein, unlike proteasomes from P0 overexpression, which appeared normal...
October 27, 2017: Glia
https://www.readbyqxmd.com/read/29074197/mitochondrial-dysfunction-perturbations-of-mitochondrial-dynamics-and-biogenesis-involved-in-endothelial-injury-induced-by-silica-nanoparticles
#6
Caixia Guo, Ji Wang, Li Jing, Ru Ma, Xiaoying Liu, Lifang Gao, Lige Cao, Junchao Duan, Xianqing Zhou, Yanbo Li, Zhiwei Sun
As silica nanoparticles (SiNPs) pervade the global economy, however, the followed emissions during the manufacturing, use, and disposal stages inevitably bring an environmental release, potentially result in harmful impacts. Endothelial dysfunction precedes cardiovascular disease, and is often accompanied by mitochondrial impairment and dysfunction. We had reported endothelial dysfunction induced by SiNPs, however, the related mechanisms by which SiNPs interact with mitochondria are not well understood. In the present study, we examined SiNPs-induced mitochondrial dysfunction, and further demonstrated their adverse effects on mitochondrial dynamics and biogenesis in endothelial cells (HUVECs)...
October 24, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29058170/pam-ola-and-lna-are-differentially-taken-up-and-trafficked-via-different-metabolic-pathways-in-porcine-adipocytes
#7
Caihua Yu, Lingling Xi, Jin Chen, Qin Jiang, Hongbo Yi, Yizhen Wang, Xinxia Wang
Dietary fatty acids have different effects on fat deposition in pigs. To clarify the underlying mechanisms of this difference, we compared the metabolism of palmitic (PAM, saturated), oleic (OLA, monounsaturated) and linoleic acid (LNA, polyunsaturated) in porcine adipocytes treated with 100 μM PAM, OLA or LNA. We observed that the adipocytes incubated with LNA accumulated more lipids compared with those treated with PAM and OLA. We then probed the metabolism of these fatty acids in porcine adipocytes by using isotope-labelled fatty acids...
November 2017: Lipids
https://www.readbyqxmd.com/read/29051032/fth1-expression-is-affected-by-promoter-polymorphism-and-not-dna-methylation-in-response-to-dhv-1-challenge-in-duck
#8
Qi Xu, Tiantian Gu, Ran Liu, Zhengfeng Cao, Yu Zhang, Yang Chen, Ningzhao Wu, Guohong Chen
Ferritin heavy polypeptide 1 (FTH1) plays a pivotal role in response to viral infections. FTH1 expression is modulated by various pathogens, but the regulatory mechanisms are unknown. We firstly construct duck hepatitis virus 1 (DHV-1) infection model, including morbid ducklings, non-morbid ducklings and control ducklings. Then the mRNA expression of duck FTH1 (duFTH1) was measured mRNA expression of duck FTH1 (duFTH1) in the liver and spleen after duck hepatitis virus 1 (DHV-1) infection using quantitative polymerase chain reaction (qPCR) and found that duFTH1 mRNA was down-regulated significantly in morbid ducklings (liver, P < 0...
October 16, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29030114/impairment-of-energy-sensors-sirt1-and-ampk-in-lipid-induced-inflamed-adipocyte-is-regulated-by-fetuin-a
#9
Mrittika Chattopadhyay, Sandip Mukherjee, Subhendu K Chatterjee, Dipanjan Chattopadhyay, Snehasis Das, Subeer S Majumdar, Satinath Mukhopadhyay, Sutapa Mukherjee, Samir Bhattarcharya
Although several reports demonstrated that accumulation of excess lipid in adipose tissue produces defects in adipocyte which leads to the disruption of energy homeostasis causing severe metabolic problems, underlying mechanism of this event remains yet unclear. Here we demonstrate that FetuinA (FetA) plays a critical role in the impairment of two metabolic sensors, SIRT1 and AMPK, in inflamed adipocytes of high fat diet (HFD) mice. A linear increase in adipocyte hypertrophy from 10 to 16 week was in tandem with the increase in FetA and that coincided with SIRT1 cleavage and decrease in pAMPK which adversely affects PGC1α activation...
October 10, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28986187/aldose-reductase-inhibitor-fidarestat-regulates-mitochondrial-biogenesis-via-nrf2-ho-1-ampk-pathway-in-colon-cancer-cells
#10
Kirtikar Shukla, Himangshu Sonowal, Ashish Saxena, Kota V Ramana, Satish K Srivastava
Although we have shown earlier that aldose reductase (AR) inhibitors prevent colorectal cancer cell (CRC) growth in culture as well as in nude mice xenografts, the mechanism(s) is not well understood. In this study, we have investigated how AR inhibition prevents CRC growth by regulating the mitochondrial biogenesis via Nrf2/HO-1 pathway. Incubation of CRC cells such as SW-480, HT29, and HCT116 with AR inhibitor, fidarestat that non-covalently binds to the enzyme, increases the expression of Nrf2. Further, fidarestat augmented the EGF-induced expression of Nrf2 in CRC cells...
December 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28884876/intranasal-insulin-treatment-restores-cognitive-deficits-and-insulin-signaling-impairment-induced-by-repeated-methamphetamine-exposure
#11
Elmira Beirami, Shahrbanoo Oryan, Seyedeh Masoumeh Seyedhosseini Tamijani, Abolhassan Ahmadiani, Leila Dargahi
Long-term use of methamphetamine (MA) causes a broad range of cognitive deficits. Recently, it has been reported insulin signaling and mitochondrial biogenesis are involved in cognitive processes. This study aimed to examine whether MA induces cognitive deficits concomitant with insulin signaling impairment and mitochondrial dysfunctions and also intranasal (IN) insulin treatment can reverse cognitive deficits caused by MA. Rats were repeatedly treated with increasing doses of MA (1-10 mg/kg) twice a day for 10 days, and their cognitive functions were assessed using Y-maze, novel object recognition and passive avoidance tasks...
September 8, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28878026/the-p97-inhibitor-cb-5083-is-a-unique-disrupter-of-protein-homeostasis-in-models-of-multiple-myeloma
#12
Ronan Le Moigne, Blake T Aftab, Stevan Djakovic, Eugen Dhimolea, Eduardo Valle, Megan Murnane, Emily M King, Ferdie Soriano, Mary-Kamala Menon, Zhi Yong Wu, Stephen T Wong, Grace J Lee, Bing Yao, Arun P Wiita, Christine Lam, Julie Rice, Jinhai Wang, Marta Chesi, P Leif Bergsagel, Marianne Kraus, Christoph Driessen, Szerenke Kiss von Soly, F Michael Yakes, David Wustrow, Laura Shawver, Han-Jie Zhou, Thomas G Martin, Jeffrey L Wolf, Constantine S Mitsiades, Daniel J Anderson, Mark Rolfe
Inhibition of the AAA ATPase, p97, was recently shown to be a novel method for targeting the ubiquitin proteasome system, and CB-5083, a first-in-class inhibitor of p97, has demonstrated broad antitumor activity in a range of both hematologic and solid tumor models. Here, we show that CB-5083 has robust activity against multiple myeloma cell lines and a number of in vivo multiple myeloma models. Treatment with CB-5083 is associated with accumulation of ubiquitinated proteins, induction of the unfolded protein response, and apoptosis...
November 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28875237/uncoupling-protein-2-inhibition-exacerbates-glucose-fluctuation-mediated-neuronal-effects
#13
Susana Cardoso, Raquel M Seiça, Paula I Moreira
Though glucose fluctuations have been considered as an adverse factor for the development of several diabetes-related complications, their impact in the central nervous system is still not fully elucidated. This study was conducted to evaluate the responses of neuronal cells to different glycemic exposures alongside to elucidate the role of uncoupling protein 2 (UCP2) in regulating such responses. To achieve our goals, primary cortical neurons were submitted to constant high (HG)/low (LG) or glucose level variations (GVs), and the pharmacological inhibition of UCP2 activity was performed using genipin...
September 5, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28863367/monomeric-cocoa-catechins-enhance-%C3%AE-cell-function-by-increasing-mitochondrial-respiration
#14
Thomas J Rowley, Benjamin F Bitner, Jason D Ray, Daniel R Lathen, Andrew T Smithson, Blake W Dallon, Chase J Plowman, Benjamin T Bikman, Jason M Hansen, Melanie R Dorenkott, Katheryn M Goodrich, Liyun Ye, Sean F O'Keefe, Andrew P Neilson, Jeffery S Tessem
A hallmark of type 2 diabetes (T2D) is β-cell dysfunction and the eventual loss of functional β-cell mass. Therefore, mechanisms that improve or preserve β-cell function could be used to improve the quality of life of individuals with T2D. Studies have shown that monomeric, oligomeric and polymeric cocoa flavanols have different effects on obesity, insulin resistance and glucose tolerance. We hypothesized that these cocoa flavanols may have beneficial effects on β-cell function. INS-1 832/13-derived β-cells and primary rat islets cultured with a monomeric catechin-rich cocoa flavanol fraction demonstrated enhanced glucose-stimulated insulin secretion, while cells cultured with total cocoa extract and with oligomeric or polymeric procyanidin-rich fraction demonstrated no improvement...
November 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28831286/standardized-kaempferia-parviflora-extract-inhibits-intrinsic-aging-process-in-human-dermal-fibroblasts-and-hairless-mice-by-inhibiting-cellular-senescence-and-mitochondrial-dysfunction
#15
Ji-Eun Park, Seon Wook Woo, Mi-Bo Kim, Changhee Kim, Jae-Kwan Hwang
Intrinsic skin aging is a complex biological phenomenon mainly caused by cellular senescence and mitochondrial dysfunction. This study evaluated the inhibitory effect of Kaempferia parviflora Wall ex. Baker ethanol extract (KPE) on H2O2-stimulated cellular senescence and mitochondrial dysfunction both in vitro and in vivo. KPE significantly increased cell growth and suppressed senescence-associated β-galactosidase activation. KPE inhibited the expression of cell-cycle inhibitors (p53, p21, p16, and pRb) and stimulated the expression of cell-cycle activators (E2F1 and E2F2)...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28807877/cryptotanshinone-promotes-commitment-to-the-brown-adipocyte-lineage-and-mitochondrial-biogenesis-in-c3h10t1-2-mesenchymal-stem-cells-via-ampk-and-p38-mapk-signaling
#16
Khan Mohammad Imran, Naimur Rahman, Dahyeon Yoon, Miso Jeon, Byong-Taek Lee, Yong-Sik Kim
Although white adipose tissue (WAT) stores triglycerides and contributes to obesity, brown adipose tissue (BAT) dissipates energy as heat. Therefore, browning of WAT is regarded as an attractive way to counteract obesity. Our previous studies have revealed that treatment with cryptotanshinone (CT) during adipogenesis of 3T3-L1 cells inhibits their differentiation. Here, we found that pretreatment of C3H10T1/2 mesenchymal stem cells with CT before exposure to adipogenic hormonal stimuli promotes the commitment of these mesenchymal stem cells to the adipocyte lineage as confirmed by increased triglyceride accumulation...
October 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28801681/nrf1-and-zscan10-bind-to-the-promoter-region-of-the-six1-gene-and-their-effects-body-measurements-in-qinchuan-cattle
#17
Da-Wei Wei, Lin-Sheng Gui, Sayed Haidar Abbas Raza, Song Zhang, Rajwali Khan, Li Wang, Hong-Fang Guo, Lin-Sen Zan
The SIX1 homeobox gene belongs to the six homeodomain family and is widely thought to play a principal role in mediating of skeletal muscle development. In the present study, we determined that the bovine SIX1 gene was highly expressed in the longissimus thoracis and physiologically immature individuals. DNA sequencing of 428 individual Qinchuan cattle identified nine single nucleotide polymorphisms (SNPs) in the promoter region of the SIX1 gene. Using a series of 5' deletion promoter plasmid luciferase reporter assays and 5'-rapid amplification of cDNA end analysis (RACE), two of these SNPs were found to be located in the proximal minimal promoter region -216/-28 relative to the transcriptional start site (TSS)...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790926/moderate-exercise-allows-for-shorter-recovery-time-in-critical-limb-ischemia
#18
Anne Lejay, Gilles Laverny, Stéphanie Paradis, Anna-Isabel Schlagowski, Anne-Laure Charles, François Singh, Joffrey Zoll, Fabien Thaveau, Evelyne Lonsdorfer, Stéphane Dufour, Fabrice Favret, Valérie Wolff, Daniel Metzger, Nabil Chakfe, Bernard Geny
Whether and how moderate exercise might allow for accelerated limb recovery in chronic critical limb ischemia (CLI) remains to be determined. Chronic CLI was surgically induced in mice, and the effect of moderate exercise (training five times per week over a 3-week period) was investigated. Tissue damages and functional scores were assessed on the 4th, 6th, 10th, 20th, and 30th day after surgery. Mice were sacrificed 48 h after the last exercise session in order to assess muscle structure, mitochondrial respiration, calcium retention capacity, oxidative stress and transcript levels of genes encoding proteins controlling mitochondrial functions (PGC1α, PGC1β, NRF1) and anti-oxidant defenses markers (SOD1, SOD2, catalase)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28754714/nrf1-coordinates-with-dna-methylation-to-regulate-spermatogenesis
#19
Junpeng Wang, Chao Tang, Qian Wang, Jun Su, Ting Ni, Wenjing Yang, Yongsheng Wang, Wei Chen, Xiqiang Liu, Shuai Wang, Jingjing Zhang, Huili Song, Jun Zhu, Yuan Wang
Spermatogenesis is a highly coordinated process that requires tightly regulated gene expression programmed by transcription factors and epigenetic modifiers. In this study, we found that nuclear respiratory factor (NRF)-1, a key transcription factor for mitochondrial biogenesis, cooperated with DNA methylation to directly regulate the expression of multiple germ cell-specific genes including Asz1 In addition, conditional ablation of NRF1 in gonocytes dramatically down-regulated these germline genes, blocked germ cell proliferation, and subsequently led to male infertility in mice...
July 28, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28715885/the-effects-of-exercise-and-cold-exposure-on-mitochondrial-biogenesis-in-skeletal-muscle-and-white-adipose-tissue
#20
Nana Chung, Jonghoon Park, Kiwon Lim
PURPOSE: The purpose of this study was to determine whether exercise or/and cold exposure regulate mitochondria biogenesis-related gene expression in soleus and inguinal adipose tissue of mice. METHODS: Forty ICR 5-week old male mice were divided into four groups: thermoneutrality-untrained (23 ± 1 °C in room temperature, n=10), cold-water immersion (24 ± 1 °C, n=10), exercise in neutral temperature (34 ± 1 °C, n=10), and exercise in cold temperature (24 ± 1 °C, n=10)...
June 30, 2017: Journal of Exercise Nutrition & Biochemistry
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