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https://www.readbyqxmd.com/read/29902460/the-anti-malarial-atovaquone-selectively-increases-chemosensitivity-in-retinoblastoma-via-mitochondrial-dysfunction-dependent-oxidative-damage-and-akt-ampk-mtor-inhibition
#1
Feng Ke, Jinqiang Yu, Wei Chen, Xiaomin Si, Xinhui Li, Fang Yang, Yingying Liao, Zhigang Zuo
Mitochondria has been identified as a promising target in several cancers. However, little is known on the effects of targeting mitochondria in retinoblastoma. In this work, we show that anti-malarial atovaquone, at clinically achievable concentration, demonstrates inhibitory effects to retinoblastoma cells, to a more extent than in normal retinal cells. Atovaquone also significantly increases chemosensitivity in retinoblastoma. Importantly, we show that retinoblastoma cells have higher level of mitochondrial respiration, membrane potential, mass and ATP compared to normal retinal cells...
June 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29899732/3-5-diiodo-l-thyronine-increases-glucose-consumption-in-cardiomyoblasts-without-affecting-the-contractile-performance-in-rat-heart
#2
Ginevra Sacripanti, Nhat Minh Nguyen, Leonardo Lorenzini, Sabina Frascarelli, Alessandro Saba, Riccardo Zucchi, Sandra Ghelardoni
3,5-diiodo-l-thyronine (T2) is an endogenous derivative of thyroid hormone that has been suggested to regulate energy expenditure, resting metabolic rate and oxygen consumption with a mechanism that involves the activation of mitochondrial function. In this study, we focused on the cardiac effects of T2, which have been poorly investigated so far, by using both in vitro and ex vivo models. As a comparison, the response to T3 and T4 was also determined. Rat cardiomyoblasts (H9c2 cells) were used to determine T2, T3, and T4 uptake by high-performance liquid chromatography-tandem mass spectrometry...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29896930/lower-fasted-state-but-greater-increase-in-muscle-protein-synthesis-in-response-to-elevated-plasma-amino-acids-in-obesity
#3
Lee Tran, Katon A Kras, Nyssa Hoffman, Jayachandran Ravichandran, Jared M Dickinson, Andrew D'Lugos, Chad C Carroll, Shivam H Patel, Lawrence J Mandarino, Lori Roust, Christos S Katsanos
OBJECTIVE: Obesity alters protein metabolism in skeletal muscle, but consistent evidence is lacking. This study compared muscle protein synthesis in adults with obesity and in lean controls in the fasted state and during an amino acid infusion. METHODS: Ten subjects with obesity (age: 36 ± 3 years; BMI: 34 ± 1 kg/m2 ) and ten controls (age: 35 ± 3 years; BMI: 23 ± 1 kg/m2 ) received an infusion of L-[2,3,3,4,5,5,5,6,6,6-2 H10 ]leucine (0.15 μmol/kg fat-free mass/min) to measure muscle protein synthesis after an overnight fast and during amino acid infusion...
June 12, 2018: Obesity
https://www.readbyqxmd.com/read/29896118/moderate-exercise-suppresses-nf-%C3%AE%C2%BAb-signaling-and-activates-the-sirt1-ampk-pgc1%C3%AE-axis-to-attenuate-muscle-loss-in-diabetic-db-db-mice
#4
Hung-Wen Liu, Sue-Joan Chang
The clear mechanism of moderate exercise training (Ex) in attenuating muscle loss remains elusive in diabetes. We investigated the effects of moderate exercise training on diabetes-induced nuclear factor-κB (NF-κB) activation and mitochondrial dysfunction. Skeletal muscle size and atrophy signaling pathways were examined in type 2 diabetic db/db mice with or without moderate exercise training (5.2 m/min, 1 h/day, and 5 days/week for a total of 8 weeks). Exercise training decreased serum leptin, MCP-1, and resistin levels in db/db +Ex mice, but it did not reduce symptoms of insulin resistance including hyperglycemia, hyperinsulinemia, and impaired glucose tolerance...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29895328/glucocorticoid-dependent-redd1-expression-reduces-muscle-metabolism-to-enable-adaptation-under-energetic-stress
#5
Florian A Britto, Fabienne Cortade, Yassine Belloum, Marine Blaquière, Yann S Gallot, Aurélie Docquier, Allan F Pagano, Elodie Jublanc, Nadia Bendridi, Christelle Koechlin-Ramonatxo, Béatrice Chabi, Marc Francaux, François Casas, Damien Freyssenet, Jennifer Rieusset, Sophie Giorgetti-Peraldi, Gilles Carnac, Vincent Ollendorff, François B Favier
BACKGROUND: Skeletal muscle atrophy is a common feature of numerous chronic pathologies and is correlated with patient mortality. The REDD1 protein is currently recognized as a negative regulator of muscle mass through inhibition of the Akt/mTORC1 signaling pathway. REDD1 expression is notably induced following glucocorticoid secretion, which is a component of energy stress responses. RESULTS: Unexpectedly, we show here that REDD1 instead limits muscle loss during energetic stresses such as hypoxia and fasting by reducing glycogen depletion and AMPK activation...
June 12, 2018: BMC Biology
https://www.readbyqxmd.com/read/29894202/insulin-resistance-is-a-significant-determinant-of-sarcopenia-in-advanced-kidney-disease
#6
Serpil Muge Deger, Jennifer R Hewlett, Jorge Gamboa, Charles D Ellis, Adriana M Hung, Edward D Siew, Cindy Mamnungu, Feng Sha, Aihua Bian, Thomas G Stewart, Naji N Abumrad, T Alp Ikizler
Maintenance hemodialysis (MHD) patients display significant nutritional abnormalities. Insulin is an anabolic hormone with direct effects on skeletal muscle (SM). We examined the anabolic actions of insulin, whole-body (WB) and SM protein turnover, in 33 MHD patients and 17 participants without kidney disease using hyperinsulinemic euglycemic euaminoacidemic (dual) clamp. Gluteal muscle biopsies were obtained before and after the dual-clamp. At baseline, WB protein synthesis and breakdown rates were similar in MHD patients...
June 12, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29892824/thyroid-hormone-action-the-p43-mitochondrial-pathway
#7
Chantal Wrutniak-Cabello, François Casas, Gérard Cabello
The possibility that several pathways are involved in the multiplicity of thyroid hormone physiological influences led to searches for the occurrence of T3 extra nuclear receptors. The existence of a direct T3 mitochondrial pathway is now well established. The demonstration that TRα1 mRNA encodes not only a nuclear thyroid hormone receptor but also two proteins imported into mitochondria with molecular masses of 43 and 28 kDa has provided new clues to understand the pleiotropic influence of iodinated hormones...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29891712/lipid-binding-attenuates-channel-closure-of-the-outer-membrane-protein-ompf
#8
Idlir Liko, Matteo T Degiacomi, Sejeong Lee, Thomas D Newport, Joseph Gault, Eamonn Reading, Jonathan T S Hopper, Nicholas G Housden, Paul White, Matthew Colledge, Altin Sula, B A Wallace, Colin Kleanthous, Phillip J Stansfeld, Hagan Bayley, Justin L P Benesch, Timothy M Allison, Carol V Robinson
Strong interactions between lipids and proteins occur primarily through association of charged headgroups and amino acid side chains, rendering the protonation status of both partners important. Here we use native mass spectrometry to explore lipid binding as a function of charge of the outer membrane porin F (OmpF). We find that binding of anionic phosphatidylglycerol (POPG) or zwitterionic phosphatidylcholine (POPC) to OmpF is sensitive to electrospray polarity while the effects of charge are less pronounced for other proteins in outer or mitochondrial membranes: the ferripyoverdine receptor (FpvA) or the voltage-dependent anion channel (VDAC)...
June 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29890853/numb-depletion-promotes-drp1-mediated-mitochondrial-fission-and-exacerbates-mitochondrial-fragmentation-and-dysfunction-in-acute-kidney-injury
#9
Ze Liu, Hao Li, Jianqun Su, Shihui Xu, Fengxin Zhu, Jun Ai, Zheng Hu, Miaomiao Zhou, Jianwei Tian, Zhiyuan Su, Peiliang Yang, Jing Nie
AIMS: Mitochondrial fragmentation is a crucial mechanism contributing to tubular cell apoptosis during acute kidney injury (AKI). However, the mechanism of modulating mitochondrial dynamics during AKI remains unclear. Numb is a multifunction adaptor protein that is expressed in renal tubules. The aim of the present study is to study the role of Numb in mitochondrial dysfunction during AKI. RESULTS: The expression of Numb was upregulated in both ischemia-reperfusion- and cisplatin-induced AKI...
June 11, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29890156/long-term-effects-of-neonatal-exposure-to-fluoxetine-on-energy-balance-a-systematic-review-of-experimental-studies
#10
REVIEW
Manuella da L D Barros, Raul Manhães-de-Castro, Daniele T Alves, Omar Guzmán Quevedo, Ana Elisa Toscano, Alexandre Bonnin, Ligia Galindo
Serotonin exerts a modulating function on the development of the central nervous system, including hypothalamic circuits controlling feeding behavior and energy expenditure. Based on the developmental plasticity theory, early disturbances of synaptic availability of serotonin may promote phenotypic adaptations and late disorders of energy balance regulation leading to obesity and associated diseases. The aim of this systematic review is to determine the effects of pharmacological neonatal inhibition of serotonin reuptake by fluoxetine, on parameters related to feeding behavior and energy balance...
June 8, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29889834/pathological-presentation-of-cardiac-mitochondria-in-a-rat-model-for-chronic-kidney-disease
#11
Einat Bigelman, Lena Cohen, Genya Aharon-Hananel, Ran Levy, Zach Rozenbaum, Ann Saada, Gad Keren, Michal Entin-Meer
BACKGROUND: Mitochondria hold crucial importance in organs with high energy demand especially the heart. We investigated whether chronic kidney disease (CKD), which eventually culminates in cardiorenal syndrome, could affect cardiac mitochondria and assessed the potential involvement of angiotensin II (AngII) in the process. METHODS: Male Lewis rats underwent 5/6 nephrectomy allowing CKD development for eight months or for eleven weeks. Short-term CKD rats were administered with AngII receptor blocker (ARB)...
2018: PloS One
https://www.readbyqxmd.com/read/29888783/a-novel-inhibitor-of-inos-dimerization-protects-against-cytokine-induced-rat-%C3%AE-cell-dysfunction
#12
Linlin Zhong, Tuan Tran, Tyler D Baguley, Sang Jun Lee, Adam Henke, Andrew To, Sijia Li, Shan Yu, Fabio A Grieco, Jason Roland, Peter G Schultz, Decio L Eizirik, Nikki Rogers, Arnab K Chartterjee, Matthew S Tremblay, Weijun Shen
BACKGROUND AND PURPOSE: β-cell apoptosis is a major feature of type 1 diabetes and pro-inflammatory cytokines are key drivers of the deterioration of β-cell mass through induction of apoptosis. Mitochondrial stress plays a critical role in mediating apoptosis by releasing cytochrome C into the cytoplasm, directly activating caspase-9 and its downstream signaling cascade. We aim to identify new compounds that protect β cells from cytokine-induced activation of the intrinsic (mitochondrial) pathway of apoptosis...
June 11, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29881815/baseline-urine-metabolic-phenotype-in-patients-with-severe-alcoholic-hepatitis-and-its-association-with-outcome
#13
Jaswinder Singh Maras, Sukanta Das, Shvetank Sharma, Saggere M Shasthry, Benoit Colsch, Christophe Junot, Richard Moreau, Shiv Kumar Sarin
Severe alcoholic hepatitis (SAH) has a high mortality rate, and corticosteroid therapy is effective in 60% patients. This study aimed to investigate a baseline metabolic phenotype that could help stratify patients not likely to respond to steroid therapy and to have an unfavorable outcome. Baseline urine metabolome was studied in patients with SAH using ultra-high performance liquid chromatography and high-resolution mass spectrometry. Patients were categorized as responders (Rs, n = 52) and nonresponders (NRs, n = 8) at day 7 according to the Lille score...
June 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29879809/polymorphisms-in-the-uncoupling-protein-3-gene-and-their-associations-with-feed-efficiency-in-chickens
#14
Sihua Jin, Lei Yang, Tingting He, Xinfeng Fan, Yiqiu Wang, Kai Ge, Zhaoyu Geng
Objective: The uncoupling protein 3 (UCP3) is a member of the mitochondrial anion carrier superfamily and has crucial effects on growth and feed efficiency in many species. Therefore, the objective of the present study was to examine the association of polymorphisms in the UCP3 gene with feed efficiency in meat-type chickens. Methods: Six SNPs of the UCP3 gene were chosen to be genotyped using matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) in meat-type chicken populations with 724 birds in total...
May 31, 2018: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/29879550/loss-of-the-ubiquitin-conjugating-enzyme-ube2e3-induces-cellular-senescence
#15
Kendra S Plafker, Katarzyna Zyla, William Berry, Scott M Plafker
Cellular senescence plays essential roles in tissue homeostasis as well as a host of diseases ranging from cancers to age-related neurodegeneration. Various molecular pathways can induce senescence and these different pathways dictate the phenotypic and metabolic changes that accompany the transition to, and maintenance of, the senescence state. Here, we describe a novel senescence phenotype induced by depletion of UBE2E3, a highly-conserved, metazoan ubiquitin conjugating enzyme. Cells depleted of UBE2E3 become senescent in the absence of overt DNA damage and have a distinct senescence-associated secretory phenotype, increased mitochondrial and lysosomal mass, an increased sensitivity to mitochondrial and lysosomal poisons, and an increased basal autophagic flux...
May 21, 2018: Redox Biology
https://www.readbyqxmd.com/read/29878388/dietary-micronutrients-promote-neuronal-differentiation-by-modulating-the-mitochondrial-nuclear-dialogue
#16
REVIEW
Kui Xie, Allan Sheppard
The metabolic requirements of differentiated neurons are significantly different from that of neuronal precursor and neural stem cells. While a re-programming of metabolism is tightly coupled to the neuronal differentiation process, whether shifts in mitochondrial mass, glycolysis, and oxidative phosphorylation are required (or merely consequential) in differentiation is not yet certain. In addition to providing more energy, enhanced metabolism facilitates differentiation by supporting increased neurotransmitter signaling and underpinning epigenetic regulation of gene expression...
June 7, 2018: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/29874585/sam50-regulates-pink1-parkin-mediated-mitophagy-by-controlling-pink1-stability-and-mitochondrial-morphology
#17
Fenglei Jian, Dan Chen, Li Chen, Chaojun Yan, Bin Lu, Yushan Zhu, Shi Chen, Anbing Shi, David C Chan, Zhiyin Song
PINK1 and Parkin mediate mitophagy, the cellular process that clears dysfunctional mitochondria. Mitophagy is regulated by mitochondrial dynamics, but the molecules linking these two processes remain poorly understood. Here, we show that Sam50, the core component of the sorting and assembly machinery (SAM), is a critical regulator of mitochondrial dynamics and PINK1-Parkin-mediated mitophagy. In response to Sam50 depletion, normal tubular mitochondria are first fragmented and subsequently merged into large spheres...
June 5, 2018: Cell Reports
https://www.readbyqxmd.com/read/29872222/functional-characterization-of-lysosomal-interaction-of-akt-with-vrk2
#18
Noriyuki Hirata, Futoshi Suizu, Mami Matsuda-Lennikov, Tsutomu Tanaka, Tatsuma Edamura, Satoko Ishigaki, Thoria Donia, Pathrapol Lithanatudom, Chikashi Obuse, Toshihiko Iwanaga, Masayuki Noguchi
Serine-threonine kinase Akt (also known as PKB, protein kinase B), a core intracellular mediator of cell survival, is involved in various human cancers and has been suggested to play an important role in the regulation of autophagy in mammalian cells. Nonetheless, the physiological function of Akt in the lysosomes is currently unknown. We have reported previously that PtdIns(3)P-dependent lysosomal accumulation of the Akt-Phafin2 complex is a critical step for autophagy induction. Here, to characterize the molecular function of activated Akt in the lysosomes in the process of autophagy, we searched for the molecules that interact with the Akt complex at the lysosomes after induction of autophagy...
June 5, 2018: Oncogene
https://www.readbyqxmd.com/read/29872014/lupeol-induces-s-phase-arrest-and-mitochondria-mediated-apoptosis-in-cervical-cancer-cells
#19
Nupoor Prasad, Akash Sabarwal, Umesh C S Yadav, Rana P Singh
Cervical cancer is fourth most common fatal cancer in women worldwide. Lupeol is a dietary triterpenoid and has shown its anticancer efficacy against various cancer types with selectivity in targeting cancer cells. In the present study, anticancer efficacy and mechanism of action of a phytochemical, lupeol, in human cervical carcinoma (HeLa) cells has been examined. The anticancer efficacy of lupeol was assessed by trypan blue cell counting, annexin Vassay, cell cycle analysis, expression of apoptotic proteins by RT-PCR and Western blotting and assessment of mitochondrial ROS generation by mitosox and mitotracker assays...
June 2018: Journal of Biosciences
https://www.readbyqxmd.com/read/29867124/comp-prohibitin-2-interaction-maintains-mitochondrial-homeostasis-and-controls-smooth-muscle-cell-identity
#20
Yiting Jia, Meili Wang, Chenfeng Mao, Fang Yu, Yingbao Wang, Rui Xiao, Changtao Jiang, Lemin Zheng, Qingbo Xu, Ming Zheng, Yi Fu, Qinghua Hu, Wei Kong
Vascular smooth muscle cells (VSMCs) are highly phenotypically plastic, and loss of the contractile phenotype in VSMCs has been recognized at the early onset of the pathology of a variety of vascular diseases. However, the endogenous regulatory mechanism to maintain contractile phenotype in VSMCs remains elusive. Moreover, little has been known about the role of the mitochondrial bioenergetics in terms of VSMC homeostasis. Herein, we asked if glycoprotein COMP (Cartilage oligomeric matrix protein) is involved in mitochondrial bioenergetics and therefore regulates VSMCs homeostasis...
June 4, 2018: Cell Death & Disease
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