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https://www.readbyqxmd.com/read/29730257/regulation-of-the-antioxidant-response-by-myod-transcriptional-coactivator-in-castration-resistant-prostate-cancer-cells
#1
Shun Zhang, Lin-Hu Li, Hong-Mei Qiao, Xue Yang, Liang Chen, Xiao-Hui Luo
OBJECTIVE: To reveal the potential role of the basic helix-loop-helix myogenic transcription regulator MyoD in the regulation of of castration-resistant prostate cancer (CRPC). METHODS: Expression levels of MyoD was assessed in PCa tissues using quantitative RT-PCR (RT-qPCR) and immunohistochemistry and in experimentally induced castration-resistant LNCaP/R cells using RT-qPCR and immunoblotting. Effect of MyoD knockdown on LNCaP/R cells progression was determined by assessing cell proliferation, apoptosis and colony formation rate...
May 3, 2018: Urology
https://www.readbyqxmd.com/read/29729358/doxorubicin-induced-mitophagy-and-mitochondrial-damage-is-associated-with-dysregulation-of-the-pink1-parkin-pathway
#2
Jian Yin, Jiabin Guo, Qiang Zhang, Lan Cui, Li Zhang, Tingfen Zhang, Jun Zhao, Jin Li, Alistair Middleton, Paul L Carmichael, Shuangqing Peng
The usefulness of doxorubicin (DOX), a potent anticancer agent, is limited by its cardiotoxicity. Mitochondria play a central role in DOX-induced cardiotoxicity though the precise mechanisms are still obscure. Increasing evidence indicates that excessive activation of mitophagy and mitochondrial dysfunction are key causal events leading to DOX-induced cardiac injury. The PINK1/parkin pathway has emerged as a critical pathway in regulation of mitophagy as well as mitochondrial function. The present study was aimed to investigate the role of PINK1/parkin pathway in DOX-induced mitochondrial damage and cardiotoxicity...
May 3, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29713129/nonalcoholic-steatohepatitis-severity-is-defined-by-a-failure-in-compensatory-antioxidant-capacity-in-the-setting-of-mitochondrial-dysfunction
#3
Michelle L Boland, Stephanie Oldham, Brandon B Boland, Sarah Will, Jean-Martin Lapointe, Silvia Guionaud, Christopher J Rhodes, James L Trevaskis
AIM: To comprehensively evaluate mitochondrial (dys) function in preclinical models of nonalcoholic steatohepatitis (NASH). METHODS: We utilized two readily available mouse models of nonalcoholic fatty liver disease (NAFLD) with or without progressive fibrosis: Lepob /Lepob ( ob/ob ) and FATZO mice on high trans -fat, high fructose and high cholesterol (AMLN) diet. Presence of NASH was assessed using immunohistochemical and pathological techniques, and gene expression profiling...
April 28, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29709472/activation-of-tgr5-promotes-mitochondrial-biogenesis-in-human-aortic-endothelial-cells
#4
Lijun Zhao, Shifang Zhang
Impairment of mitochondrial biogenesis has been associated with vascular pathophysiology. The G-protein-coupled receptor (TGR5) is an important mediator of bile acid signaling and glucose metabolism. However, the effects of TGR5 on mitochondrial biogenesis in endothelial cells remain elusive. In this study, we found that activation of TGR5 using its specific agonist taurolithocholic acid (TLCA) promoted the expression of PGC-1α, a master regulator of mitochondrial biogenesis in human aortic endothelial cells (HAECs)...
April 27, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29701781/mutant-app-and-amyloid-beta-induced-defective-autophagy-mitophagy-mitochondrial-structural-and-functional-changes-and-synaptic-damage-in-hippocampal-neurons-from-alzheimer-s-disease
#5
P Hemachandra Reddy, XiangLin Yin, Maria Manczak, Subodh Kumar, Pradeepkiran Jangampalli Adi, Murali Vijayan, Arubala P Reddy
The purpose of our study was to determine the toxic effects of hippocampal mutant APP and amyloid beta (Aβ) in human mutant APP (mAPP) cDNA transfected with primary mouse hippocampal neurons (HT22). Hippocampal tissues are the best source of studying learning and memory functions in patients with Alzheimer's disease (AD) and healthy controls. However, investigating immortalized hippocampal neurons that express AD proteins provide an excellent opportunity for drug testing. Using quantitative RT-PCR, immunoblotting & immunofluorescence, and transmission electron microscopy, we assessed mRNA and protein levels of synaptic, autophagy, mitophagy, mitochondrial dynamics, biogenesis, dendritic protein MAP2, and assessed mitochondrial number and length in mAPP-HT22 cells that express Swedish/Indiana mutations...
April 25, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29662614/transcriptional-orchestration-of-mitochondrial-homeostasis-in-a-cellular-model-of-pgc-1-related-coactivator-dependent-thyroid-tumor
#6
Solenne Dumont, Soazig Le Pennec, Audrey Donnart, Raluca Teusan, Marja Steenman, Catherine Chevalier, Rémi Houlgatte, Frédérique Savagner
The PGC-1 (Peroxisome proliferator-activated receptor Gamma Coactivator-1) family of coactivators (PGC-1α, PGC-1β, and PRC) plays a central role in the transcriptional control of mitochondrial biogenesis and oxidative phosphorylation (OXPHOS) processes. These coactivators integrate mitochondrial energy production into cell metabolism using complementary pathways. The XTC.UC1 cell line is a mitochondria-rich model of thyroid tumors whose biogenesis is almost exclusively dependent on PRC. Here we aim to propose an integrative view of the cellular pathways regulated by PRC through integration of cDNA and miRNA microarray data and chromatin immunoprecipitation results obtained from XTC...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29650039/carbon-black-suppresses-the-osteogenesis-of-mesenchymal-stem-cells-the-role-of-mitochondria
#7
Yulai Shen, Lu Wu, Dongdong Qin, Yankai Xia, Zhu Zhou, Xuemei Zhang, Xin Wu
BACKGROUND: The rapid increase in carbon black poses threats to human health. We evaluated the effect of CB (Printex 90) on the osteogenesis of bone-marrow-derived mesenchymal stem cells (MSCs). Mitochondria play an important role in the osteogenesis of MSCs and are potential targets of nanomaterials, so we studied the role of mitochondria in the CB Printex 90-induced effects on osteogenesis. RESULTS: Low doses of Printex 90 (3 ng/mL and 30 ng/mL) that did not cause deleterious effects on MSCs' viability significantly inhibited osteogenesis of MSCs...
April 12, 2018: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/29625129/a-negative-feedback-loop-between-microrna-378-and-nrf1-promotes-the-development-of-hepatosteatosis-in-mice-treated-with-a-high-fat-diet
#8
Tianpeng Zhang, Xiaoling Zhao, Clifford J Steer, Guiqin Yan, Guisheng Song
BACKGROUNDS: The incidence of nonalcoholic fatty liver disease (NAFLD) is rapidly increasing due to the prevalence of obesity. NAFLD is a major risk factor of hepatocellular carcinoma (HCC). Even with successful surgical removal, the presence of NAFLD is associated with an increased recurrence of HCC. Despite the extensive study of NAFLD, its underlying mechanism(s) remains essentially unknown and there are no FDA-approved drugs for its treatment. Alterations in microRNA (miR) expression have been observed in human fatty livers...
April 3, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29535191/rapid-induction-of-p62-and-gabarapl1-upon-proteasome-inhibition-promotes-survival-before-autophagy-activation
#9
Zhe Sha, Helena M Schnell, Kerstin Ruoff, Alfred Goldberg
Proteasome inhibitors are used as research tools and to treat multiple myeloma, and proteasome activity is diminished in several neurodegenerative diseases. We therefore studied how cells compensate for proteasome inhibition. In 4 h, proteasome inhibitor treatment caused dramatic and selective induction of GABARAPL1 (but not other autophagy genes) and p62 , which binds ubiquitinated proteins and GABARAPL1 on autophagosomes. Knockdown of p62 or GABARAPL1 reduced cell survival upon proteasome inhibition. p62 induction requires the transcription factor nuclear factor (erythroid-derived 2)-like 1 (Nrf1), which simultaneously induces proteasome genes...
May 7, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29487387/drugging-the-lncrna-malat1-via-lna-gapmer-aso-inhibits-gene-expression-of-proteasome-subunits-and-triggers-anti-multiple-myeloma-activity
#10
Nicola Amodio, Maria Angelica Stamato, Giada Juli, Eugenio Morelli, Mariateresa Fulciniti, Martina Manzoni, Elisa Taiana, Luca Agnelli, Maria Eugenia Gallo Cantafio, Enrica Romeo, Lavinia Raimondi, Daniele Caracciolo, Valeria Zuccalà, Marco Rossi, Antonino Neri, Nikhil C Munshi, Pierosandro Tagliaferri, Pierfrancesco Tassone
The biological role and therapeutic potential of long non-coding RNAs (lncRNAs) in multiple myeloma (MM) are still to be investigated. Here, we studied the functional significance and the druggability of the oncogenic lncRNA MALAT1 in MM. Targeting MALAT1 by novel LNA-gapmeR antisense oligonucleotide antagonized MM cell proliferation and triggered apoptosis both in vitro and in vivo in a murine xenograft model of human MM. Of note, antagonism of MALAT1 downmodulated the two major transcriptional activators of proteasome subunit genes, namely NRF1 and NRF2, and resulted in reduced trypsin, chymotrypsin and caspase-like proteasome activities and in accumulation of polyubiquitinated proteins...
February 22, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29464885/effect-of-roux-en-y-gastric-bypass-on-liver-mitochondrial-dynamics-in-a-rat-model-of-obesity
#11
Jessica Sacks, Anny Mulya, Ciaran E Fealy, Hazel Huang, John D Mosinski, Mangesh R Pagadala, Hideharu Shimizu, Esam Batayyah, Philip R Schauer, Stacy A Brethauer, John P Kirwan
Bariatric surgery provides significant and durable improvements in glycemic control and hepatic steatosis, but the underlying mechanisms that drive improvements in these metabolic parameters remain to be fully elucidated. Recently, alterations in mitochondrial morphology have shown a direct link to nutrient adaptations in obesity. Here, we evaluate the effects of Roux-en-Y gastric bypass (RYGB) surgery on markers of liver mitochondrial dynamics in a diet-induced obesity Sprague-Dawley (SD) rat model. Livers were harvested from adult male SD rats 90-days after either Sham or RYGB surgery and continuous high-fat feeding...
February 2018: Physiological Reports
https://www.readbyqxmd.com/read/29434836/increased-expression-of-mitochondrial-transcription-factor-a-and-nuclear-respiratory-factor-1-predicts-a-poor-clinical-outcome-of-breast-cancer
#12
Wei Gao, Meihong Wu, Ning Wang, Yingyi Zhang, Jing Hua, Gusheng Tang, Yajie Wang
Nuclear respiratory factor-1 (Nrf1) and mitochondrial transcription factor A (TFAM) are involved in the regulation of a variety of mitochondrial functional genes, which are associated with decreased sensitivity of tumor cells to chemotherapy. However, the expression status of Nrf1 and TFAM, as well as their clinical significance in breast cancer, is unknown. In the present study, tumor tissues and corresponding adjacent normal tissues were collected from 336 patients with breast cancer, and Nrf1 and TFAM expression was analyzed by immunohistochemistry using a tissue microarray...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29433395/chicoric-acid-improves-heart-and-blood-responses-to-hypobaric-hypoxia-in-tibetan-yaks
#13
Hua Wu, Dan Luo, Changxing Li, Hui Zhang, A Shunxian, Yuanxin Zhang, Chao Sun
Yak is a wild bovine species living on the Qinghai Tibet Plateau that demonstrates good adaptability to the hypoxic environment. Chicoric acid, a natural phenolic compound, is known as having anti-oxidant, antiviral, anti-inflammatory and analgesic properties. However, its effect on hypoxia adaptability of yak is still unclear. In this study 40 yaks were selected that were of similar age, parity and weight, and divided into the control group and experimental groups 1, 2, 3, randomly. Results showed that chicoric acid significantly improved RBC, HGB, and WBC...
2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29432738/humanin-promotes-mitochondrial-biogenesis-in-pancreatic-min6-%C3%AE-cells
#14
Qingqing Qin, Jieqiong Jin, Fang He, Yongqin Zheng, Tingting Li, Yun Zhang, Jundong He
Mitochondrial dysfunction is associated with β-cell failure and insulin resistance in diabetes. Humanin is an endogenous cytoprotective peptide. In the current study, we aimed to define the effects of Humanin on mitochondrial biogenesis in pancreatic β-cells. Our findings demonstrated that Humanin treatment significantly increased the expression of PGC-1α and its downstream target genes NRF1 and TFAM in MIN6 β-cells. Notably, Humanin treatment significantly promoted mitochondrial biogenesis by increasing mitochondrial mass, elevating mtDNA/nDNA ratio, and stimulating the expression of cytochrome B, which were suppressed by the specific AMPK inhibitor compound C...
February 26, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29421237/silencing-of-long-isoforms-of-nuclear-factor-erythroid-2-like-1-primes-macrophages-towards-m1-polarization
#15
Huihui Wang, Jiayu Zhu, Zhiyuan Liu, Hang Lv, Peng Lv, Feng Chen, Jingqi Fu, Yongyong Hou, Rui Zhao, Yuanyuan Xu, Qiang Zhang, Jingbo Pi
Macrophages are a major component of the immune system and play an important role in regulating the magnitude, duration, and quality of the inflammatory response. Dissecting the functions of transcription factors regulating macrophage activation is important for understanding the inflammatory responses. Nuclear factor erythroid 2 like 1 (NFE2L1, also known as Nrf1) is a CNC-bZIP protein, which has multiple isoforms. While the exact physiological functions of various isoforms of NFE2L1 are still under investigation, accumulating evidence indicate that long isoforms of NFE2L1 (NFE2L1(L)) are important regulators in the antioxidant response, proteasome homeostasis and inflammation...
March 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29416681/changes-in-metabolism-affect-expression-of-abc-transporters-through-erk5-and-depending-on-p53-status
#16
Sana Belkahla, Abrar Ul Haq Khan, Delphine Gitenay, Catherine Alexia, Claire Gondeau, Dang-Nghiem Vo, Stefania Orecchioni, Giovanna Talarico, Francesco Bertolini, Guillaume Cartron, Javier Hernandez, Martine Daujat-Chavanieu, Nerea Allende-Vega, Martin Villalba Gonzalez
Changes in metabolism require the efflux and influx of a diverse variety of metabolites. The ABC superfamily of transporters regulates the exchange of hundreds of substrates through the impermeable cell membrane. We show here that a metabolic switch to oxidative phosphorylation (OXPHOS), either by treating cells with dichloroacetate (DCA) or by changing the available substrates, reduced expression of ABCB1, ABCC1, ABCC5 and ABCG2 in wild-type p53-expressing cells. This metabolic change reduced histone changes associated to active promoters...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29408999/hippocampal-mutant-app-and-amyloid-beta-induced-cognitive-decline-dendritic-spine-loss-defective-autophagy-mitophagy-and-mitochondrial-abnormalities-in-a-mouse-model-of-alzheimer-s-disease
#17
Maria Manczak, Ramesh Kandimalla, Xiangling Yin, P Hemachandra Reddy
The purpose of our study was to determine the toxic effects of hippocampal mutant APP and amyloid beta (Aβ) in 12-month-old APP transgenic mice. Using rotarod and Morris water maze tests, immunoblotting and immunofluorescence, Golgi-cox staining and transmission electron microscopy, we assessed cognitive behavior, protein levels of synaptic, autophagy, mitophagy, mitochondrial dynamics, biogenesis, dendritic protein MAP2 and quantified dendritic spines and mitochondrial number and length in 12-month-old APP mice that express Swedish mutation...
April 15, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29407229/combined-analysis-of-dna-methylation-and-gene-expression-profiles-of-osteosarcoma-identified-several-prognosis-signatures
#18
Wen Tian, Yongsheng Li, Jinghua Zhang, Jijun Li, Jinghua Gao
Osteosarcoma (OS) is a common primary malignancy in children and adolescents with relative high survival rate after chemotherapy. While, the toxicity of chemotherapy and personalized different response to chemotherapy makes it difficult for the selection of therapeutics and improvement of diagnosis. In this study, we conducted a combined analysis of two types of microarray datasets (gene expression and DNA methylation) from the Gene Expression Omnibus (GEO). Differential methylation sites (DMS) were identified by the IMA package and differential expression genes (DEGs) were screened out via the limma package...
April 15, 2018: Gene
https://www.readbyqxmd.com/read/29400713/brown-adipose-tissue-thermogenic-adaptation-requires-nrf1-mediated-proteasomal-activity
#19
Alexander Bartelt, Scott B Widenmaier, Christian Schlein, Kornelia Johann, Renata L S Goncalves, Kosei Eguchi, Alexander W Fischer, Günes Parlakgül, Nicole A Snyder, Truc B Nguyen, Oliver T Bruns, Daniel Franke, Moungi G Bawendi, Matthew D Lynes, Luiz O Leiria, Yu-Hua Tseng, Karen E Inouye, Ana Paula Arruda, Gökhan S Hotamisligil
Adipocytes possess remarkable adaptive capacity to respond to nutrient excess, fasting or cold exposure, and they are thus an important cell type for the maintenance of proper metabolic health. Although the endoplasmic reticulum (ER) is a critical organelle for cellular homeostasis, the mechanisms that mediate adaptation of the ER to metabolic challenges in adipocytes are unclear. Here we show that brown adipose tissue (BAT) thermogenic function requires an adaptive increase in proteasomal activity to secure cellular protein quality control, and we identify the ER-localized transcription factor nuclear factor erythroid 2-like 1 (Nfe2l1, also known as Nrf1) as a critical driver of this process...
March 2018: Nature Medicine
https://www.readbyqxmd.com/read/29385074/guarana-paullinia-cupana-stimulates-mitochondrial-biogenesis-in-mice-fed-high-fat-diet
#20
Natália da Silva Lima, Lucimara Teixeira, Alessandra Gambero, Marcelo Lima Ribeiro
The aim of this study was to evaluate the effects of guarana on mitochondrial biogenesis in a high-fat diet (HFD)-fed mice. C57BL6J mice were divided in two groups: high-fat diet HFD and high-fat diet + guarana (HFD-GUA). Both groups received HFD and water ad libitum and the HFD-GUA group also received a daily gavage of guarana (1 g/kg weight). Body weight and food intake was measured weekly. Glycemic, triglyceride, and cholesterol levels were determined. VO₂ and energy expenditure (EE) were determined by indirect calorimetry...
January 31, 2018: Nutrients
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