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inducing mitochondrial biogenesis

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https://www.readbyqxmd.com/read/28076827/new-diphenylmethane-derivatives-as-peroxisome-proliferator-activated-receptor-alpha-gamma-dual-agonists-endowed-with-anti-proliferative-effects-and-mitochondrial-activity
#1
Luca Piemontese, Carmen Cerchia, Antonio Laghezza, Pamela Ziccardi, Sabina Sblano, Paolo Tortorella, Vito Iacobazzi, Vittoria Infantino, Paolo Convertini, Fabrizio Dal Piaz, Angelo Lupo, Vittorio Colantuoni, Antonio Lavecchia, Fulvio Loiodice
We screened a short series of new chiral diphenylmethane derivatives and identified potent dual PPARα/γ partial agonists. As both enantiomers of the most active compound 1 displayed an unexpected similar transactivation activity, we performed docking experiments to provide a molecular understanding of their similar partial agonism. We also evaluated the ability of both enantiomers of 1 and racemic 2 to inhibit colorectal cancer cells proliferation: (S)-1 displayed a more robust activity due, at least in part, to a partial inhibition of the Wnt/β-catenin signalling pathway that is upregulated in the majority of colorectal cancers...
December 24, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28076790/the-anti-warburg-effect-elicited-by-the-camp-pgc1%C3%AE-pathway-drives-differentiation-of-glioblastoma-cells-into-astrocytes
#2
Fan Xing, Yizhao Luan, Jing Cai, Sihan Wu, Jialuo Mai, Jiayu Gu, Haipeng Zhang, Kai Li, Yuan Lin, Xiao Xiao, Jiankai Liang, Yuan Li, Wenli Chen, Yaqian Tan, Longxiang Sheng, Bingzheng Lu, Wanjun Lu, Mingshi Gao, Pengxin Qiu, Xingwen Su, Wei Yin, Jun Hu, Zhongping Chen, Ke Sai, Jing Wang, Furong Chen, Yinsheng Chen, Shida Zhu, Dongbing Liu, Shiyuan Cheng, Zhi Xie, Wenbo Zhu, Guangmei Yan
Glioblastoma multiforme (GBM) is among the most aggressive of human cancers. Although differentiation therapy has been proposed as a potential approach to treat GBM, the mechanisms of induced differentiation remain poorly defined. Here, we established an induced differentiation model of GBM using cAMP activators that specifically directed GBM differentiation into astroglia. Transcriptomic and proteomic analyses revealed that oxidative phosphorylation and mitochondrial biogenesis are involved in induced differentiation of GBM...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28073778/overexpression-of-pgc-1%C3%AE-increases-peroxisomal-and-mitochondrial-fatty-acid-oxidation-in-human-primary-myotubes
#3
Tai-Yu Huang, Donghai Zheng, Joseph A Houmard, Jeffrey J Brault, Robert C Hickner, Ronald N Cortright
Peroxisomes are indispensable organelles for lipid metabolism in humans and their biogenesis has been assumed to be under regulation by peroxisome proliferator-activated receptors (PPARs). However, recent studies in hepatocytes suggest that the mitochondrial proliferator PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1 alpha) also acts as an upstream transcriptional regulator for enhancing peroxisomal abundance and associated activity. It is unknown whether the regulatory mechanism(s) for enhancing peroxisomal function is through the same node as mitochondrial biogenesis in human skeletal muscle (HSkM) and whether fatty acid oxidation (FAO) is affected...
January 10, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28069382/antibiotic-tigecycline-enhances-cisplatin-activity-against-human-hepatocellular-carcinoma-through-inducing-mitochondrial-dysfunction-and-oxidative-damage
#4
Jun Tan, Meijun Song, Mi Zhou, Yaoren Hu
Targeting mitochondrial metabolism has been recently demonstrated to be a promising therapeutic strategy for the treatment of various cancer. In this work, we demonstrate that antibiotic tigecycline is selectively against hepatocellular carcinoma (HCC) through inducing mitochondrial dysfunction and oxidative damage. Tigecycline is more effective in inhibiting proliferation and inducing apoptosis of HCC than normal liver cells. Importantly, tigecycline significantly enhances the inhibitory effects of chemotherapeutic drug cisplatin in HCC in vitro and in vivo...
January 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28062576/cardiolipin-regulates-mitophagy-through-the-pkc-pathway
#5
Zheni Shen, Yiran Li, Alexander N Gasparski, Hagai Abeliovich, Miriam L Greenberg
Cardiolipin (CL), the signature phospholipid of mitochondrial membranes, is important for cardiovascular health, and perturbation of CL metabolism is implicated in cardiovascular disease (CVD). While the role of CL in mitochondrial function, biogenesis, and genome stability has been studied, recent findings indicate that it is essential for functions apart from mitochondrial bioenergetics. In this study, we report that mitophagy is perturbed in CL deficient yeast cells. Mutants of autophagy/mitophagy genes ATG8, ATG18 and ATG32 synthetically interact with CL synthase mutant crd1Δ CL-deficient cells exhibited decreased GFP-tagged mitochondrial proteins inside the vacuole and decreased free GFP, consistent with decreased mitophagy...
January 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28061861/oxidative-status-predicts-quality-in-human-mesenchymal-stem-cells
#6
Alessandro Bertolo, Simona Capossela, Gion Fränkl, Martin Baur, Tobias Pötzel, Jivko Stoyanov
BACKGROUND: Human bone marrow-derived mesenchymal stem cells (MSC) are adult progenitor cells with great potential for application in cell-based therapies. From a cell-based therapy perspective, there are two limitations to MSC use: (1) these therapies require large numbers of cells, and long-term expansion of MSC in vitro promotes replicative senescence; and (2) patient variability is a challenge for defining MSC quality standards for transplantation. This study aimed to determine whether low or high oxidative status of MSC correlate with changes in cell expansion and differentiation potentials...
January 6, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28056786/immune-adaptation-to-chronic-intense-exercise-training-new-microarray-evidence
#7
Dongmei Liu, Ru Wang, Ana R Grant, Jinming Zhang, Paul M Gordon, Yuqin Wei, Peijie Chen
BACKGROUND: Endurance exercise training, especially the high-intensity training, exhibits a strong influence on the immune system. However, the mechanisms underpinning the immune-regulatory effect of exercise remain unclear. Consequently, we chose to investigate the alterations in the transcriptional profile of blood leukocytes in young endurance athletes as compared with healthy sedentary controls, using Affymetrix human gene 1.1 ST array. RESULTS: Group differences in the transcriptome were analyzed using Intensity-based Hierarchical Bayes method followed by a Logistic Regression-based gene set enrichment method...
January 5, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28054981/the-root-extract-of-pueraria-lobata-and-its-main-compound-puerarin-prevent-obesity-by-increasing-the-energy-metabolism-in-skeletal-muscle
#8
Hyo Won Jung, An Na Kang, Seok Yong Kang, Yong-Ki Park, Mi Young Song
Radix Pueraria lobata (RP) has been reported to prevent obesity and improve glucose metabolism; however, the mechanism responsible for these effects has not been elucidated. The mechanism underlying anti-obesity effect of RP was investigated in high-fat diet (HFD) induced obese mice and skeletal muscle cells (C2C12). Five-week-old C5BL/6 mice were fed a HFD containing or not containing RP (100 or 300 mg/kg) or metformin (250 mg/kg) for 16 weeks. RP reduced body weight gain, lipid accumulation in liver, and adipocyte and blood lipid levels...
January 4, 2017: Nutrients
https://www.readbyqxmd.com/read/28053050/parkin-functionally-interacts-with-pgc-1%C3%AE-to-preserve-mitochondria-and-protect-dopaminergic-neurons
#9
Lu Zheng, Nathalie Bernard-Marissal, Norman Moullan, Davide D'Amico, Johan Auwerx, Darren J Moore, Graham Knott, Patrick Aebischer, Bernard L Schneider
To understand the cause of Parkinson's disease (PD), it is important to determine the functional interactions between factors linked to the disease. Parkin is associated to autosomal recessive early-onset PD, and controls the transcription of PGC-1α, a master regulator of mitochondrial biogenesis. These two factors functionally interact to regulate the turnover and quality of mitochondria, by increasing both mitophagic activity and mitochondria biogenesis. In cortical neurons, co-expressing PGC-1α and Parkin increases the number of mitochondria, enhances maximal respiration, and accelerates the recovery of the mitochondrial membrane potential following mitochondrial uncoupling...
January 4, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28040265/pyruvate-dehydrogenase-kinase-4-deficiency-attenuates-cisplatin-induced-acute-kidney-injury
#10
Chang Joo Oh, Chae-Myeong Ha, Young-Keun Choi, Sungmi Park, Mi Sun Choe, Nam Ho Jeoung, Yang Hoon Huh, Hyo-Jeong Kim, Hee-Seok Kweon, Ji-Min Lee, Sun Joo Lee, Jae-Han Jeon, Robert A Harris, Keun-Gyu Park, In-Kyu Lee
Clinical prescription of cisplatin, one of the most widely used chemotherapeutic agents, is limited by its side effects, particularly tubular injury-associated nephrotoxicity. Since details of the underlying mechanisms are not fully understood, we investigated the role of pyruvate dehydrogenase kinase (PDK) in cisplatin-induced acute kidney injury. Among the PDK isoforms, PDK4 mRNA and protein levels were markedly increased in the kidneys of mice treated with cisplatin, and c-Jun N-terminal kinase activation was involved in cisplatin-induced renal PDK4 expression...
December 28, 2016: Kidney International
https://www.readbyqxmd.com/read/28012150/at1-receptor-antagonist-induces-thermogenic-beige-adipocytes-in-the-inguinal-white-adipose-tissue-of-obese-mice
#11
Francielle Graus-Nunes, Tamiris Lima Rachid, Felipe de Oliveira Santos, Sandra Barbosa-da-Silva, Vanessa Souza-Mello
PURPOSE: To evaluate whether losartan is able to induce beige adipocytes formation, focusing on the thermogenic gene expression and adipocyte remodeling in the subcutaneous white adipose tissue of diet-induced obese mice. METHODS: Male C57BL/6 mice received a control diet (10% energy as lipids) or a high-fat diet (50% energy as lipids) for 10 weeks, followed by a 5-week treatment with losartan: control group, control-losartan group (10 mg/Kg/day), high-fat group and high-fat-losartan group (10 mg/Kg/day)...
December 23, 2016: Endocrine
https://www.readbyqxmd.com/read/28011087/transcription-factor-eb-controls-metabolic-flexibility-during-exercise
#12
Gelsomina Mansueto, Andrea Armani, Carlo Viscomi, Luca D'Orsi, Rossella De Cegli, Elena V Polishchuk, Costanza Lamperti, Ivano Di Meo, Vanina Romanello, Silvia Marchet, Pradip K Saha, Haihong Zong, Bert Blaauw, Francesca Solagna, Caterina Tezze, Paolo Grumati, Paolo Bonaldo, Jeffrey E Pessin, Massimo Zeviani, Marco Sandri, Andrea Ballabio
The transcription factor EB (TFEB) is an essential component of lysosomal biogenesis and autophagy for the adaptive response to food deprivation. To address the physiological function of TFEB in skeletal muscle, we have used muscle-specific gain- and loss-of-function approaches. Here, we show that TFEB controls metabolic flexibility in muscle during exercise and that this action is independent of peroxisome proliferator-activated receptor-γ coactivator1α (PGC1α). Indeed, TFEB translocates into the myonuclei during physical activity and regulates glucose uptake and glycogen content by controlling expression of glucose transporters, glycolytic enzymes, and pathways related to glucose homeostasis...
January 10, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28008171/induction-of-lipogenesis-in-white-fat-during-cold-exposure-in-mice-link-to-lean-phenotype
#13
P Flachs, K Adamcova, P Zouhar, C Marques, P Janovska, I Viegas, J G Jones, K Bardova, M Svobodova, J Hansikova, O Kuda, M Rossmeisl, U Liisberg, A G Borkowska, K Kristiansen, L Madsen, J Kopecky
Background/ObjectiveFutile substrate cycling based on lipolytic release of fatty acids (FA) from intracellular triacylglycerols (TAG) and their re-esterification (TAG/FA cycling), as well as de novo FA synthesis (DNL), represent the core energy-consuming biochemical activities of white adipose tissue (WAT). We aimed to characterize their roles in cold-induced thermogenesis and energy homeostasis.MethodsMale obesity-resistant A/J and obesity-prone C57BL/6J mice maintained at 30 °C were exposed to 6 °C for 2 or 7 days...
December 23, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/27998274/repressed-sirt1-pgc-1%C3%AE-pathway-and-mitochondrial-disintegration-in-ipsc-derived-rpe-disease-model-of-age-related-macular-degeneration
#14
Nady Golestaneh, Yi Chu, Shuk Kei Cheng, Hong Cao, Eugenia Poliakov, Daniel M Berinstein
BACKGROUND: Study of age related macular degeneration (AMD) has been hampered by lack of human models that represent the complexity of the disease. Here we have developed a human in vitro disease model of AMD to investigate the underlying AMD disease mechanisms. METHODS: Generation of iPSCs from retinal pigment epithelium (RPE) of AMD donors, age-matched normal donors, skin fibroblasts of a dry AMD patient, and differentiation of iPSCs into RPE (AMD RPE-iPSC-RPE, normal RPE-iPSC-RPE and AMD Skin-iPSC-RPE, respectively)...
December 20, 2016: Journal of Translational Medicine
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...
December 18, 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/27984195/abnormal-mitochondrial-dynamics-and-impaired-mitochondrial-biogenesis-in-trigeminal-ganglion-neurons-in-a-rat-model-of-migraine
#16
Xin Dong, Xinying Guan, Keyan Chen, Shanquan Jin, Chengyun Wang, Lanyun Yan, Zhaochun Shi, Xue Zhang, Ling Chen, Qi Wan
Accumulating evidence has demonstrated a possible role of mitochondrial dysfunction in migraine pathophysiology. Migraine sufferers exhibit impaired metabolic capacity, with an increased formation of reactive oxygen species (ROS). Mitochondrial dynamics and mitochondrial biogenesis are key processes regulating mitochondrial homeostasis. The aim of this study was to explore the alterations of mitochondrial regulatory networks in a rat model of migraine induced by repeated dural stimulation with inflammatory soup (IS)...
October 28, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27983596/estrogenic-endocrine-disrupting-chemicals-influencing-nrf1-regulated-gene-networks-in-the-development-of-complex-human-brain-diseases
#17
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/27983571/anti-fatigue-effects-of-small-molecule-oligopeptides-isolated-from-panax-ginseng-c-a-meyer-in-mice
#18
Lei Bao, Xiaxia Cai, Junbo Wang, Yuan Zhang, Bin Sun, Yong Li
Panax ginseng C. A. Meyer (ginseng) is an edible and medicinal Chinese herb, which is often used in Asian countries for physical fitness. Ginseng is reported to have a wide range of biological activity and pharmaceutical properties. There were more studies on ginsenosides and polysaccharides, but fewer studies on ginseng oligopeptides (GOP), which are small molecule oligopeptides isolated from ginseng. The present study was designed to evaluate the anti-fatigue effects of GOP in mice and explore the possible underlying mechanism...
December 13, 2016: Nutrients
https://www.readbyqxmd.com/read/27980125/warm-preconditioning-protects-against-acute-heat-induced-respiratory-dysfunction-and-delays-bleaching-in-a-symbiotic-sea-anemone
#19
Thomas D Hawkins, Mark E Warner
Preconditioning to non-stressful warming can protect some symbiotic cnidarians against the high temperature-induced collapse of their mutualistic endosymbiosis with photosynthetic dinoflagellates (Symbiodinium spp.), a process known as bleaching. Here, we sought to determine if such preconditioning is underpinned by differential regulation of aerobic respiration. We quantified in vivo metabolism and mitochondrial respiratory enzyme activity in the naturally symbiotic sea anemone Exaiptasia pallida preconditioned to 30°C for>7 weeks as well as anemones kept at 26°C...
December 15, 2016: Journal of Experimental Biology
https://www.readbyqxmd.com/read/27974504/analysis-of-the-mechanism-of-radiation-induced-upregulation-of-mitochondrial-abundance-in-mouse-fibroblasts
#20
Tohru Yamamori, Tomoya Sasagawa, Osamu Ichii, Mie Hiyoshi, Tomoki Bo, Hironobu Yasui, Yasuhiro Kon, Osamu Inanami
Mitochondria strongly contribute to the maintenance of cellular integrity through various mechanisms, including oxidative adenosine triphosphate production and calcium homeostasis regulation. Therefore, proper regulation of the abundance, distribution and activity of mitochondria is crucial for the maintenance of cellular homeostasis. Previous studies have shown that ionizing radiation (IR) alters mitochondrial functions, suggesting that mitochondria are likely to be an important target of IR. Though IR reportedly influences cellular mitochondrial abundance, the mechanism remains largely unknown...
December 14, 2016: Journal of Radiation Research
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