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https://www.readbyqxmd.com/read/29352520/ipragliflozin-improves-mitochondrial-abnormalities-in-renal-tubules-induced-by-a-high-fat-diet
#1
Susumu Takagi, Jinpeng Li, Yuta Takagaki, Munehiro Kitada, Kyoko Nitta, Toshiyuki Takasu, Keizo Kanasaki, Daisuke Koya
OBJECTIVE: Complete mechanisms of reno-protective effects of SGLT2 inhibitors have not been elucidated yet. Mitochondrial biogenesis is regulated by membrane GTPases, such as Opa1 and Mfn2. Here, we investigated whether SGLT2 inhibition in mice fed with a high-fat diet (HFD) improved mitochondrial morphology and restored mitochondrial biogenesis-related molecules. MATERIALS AND METHODS: Mice were fed in control diet or HFD with or without ipragliflozin treatment...
January 20, 2018: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29351884/crucial-role-of-chelatable-iron-in-silver-nanoparticles-induced-dna-damage-and-cytotoxicity
#2
Agnieszka Grzelak, Maria Wojewódzka, Sylwia Meczynska-Wielgosz, Mariusz Zuberek, Dominika Wojciechowska, Marcin Kruszewski
Damage to mitochondria and subsequent ROS leakage is a commonly accepted mechanism of nanoparticle toxicity. However, malfunction of mitochondria results in generation of superoxide anion radical (O2•-), which due to the relatively low chemical reactivity is rather unlikely to cause harmful effects triggered by nanoparticles. We show that treatment of HepG2 cells with silver nanoparticles (AgNPs) resulted in generation of H2O2 instead of O2•-, as measured by ROS specific mitochondrial probes. Moreover, addition of a selective iron chelator diminished AgNPs toxicity...
January 9, 2018: Redox Biology
https://www.readbyqxmd.com/read/29351463/intermediary-metabolism-and-fatty-acid-oxidation-novel-targets-of-electron-transport-chain-driven-injury-during-ischemia-and-reperfusion
#3
Qun Chen, Masood S Younus, Jeremy Thompson, Ying Hu, John M Hollander, Edward J Lesnefsky
BACKGROUND: Cardiac ischemia-reperfusion (IR) damages the electron transport chain (ETC) causing mitochondrial and cardiomyocyte injury. Reversible blockade of the ETC at complex I during ischemia protects the ETC and decreases cardiac injury. In the present study, we used an unbiased proteomic approach to analyze the extent of ETC-driven mitochondrial injury during IR. METHODS: Isolated-perfused mouse (C57BL/6) hearts underwent 25 min global ischemia (37{degree sign}C) and 30 min reperfusion...
December 29, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351413/mitochondrial-content-is-preserved-throughout-disease-progression-in-the-mdx-mouse-model-of-duchenne-muscular-dystrophy-regardless-of-taurine-supplementation
#4
Robert G Barker, Victoria L Wyckelsma, Hongyang Xu, Robyn M Murphy
Mitochondrial dysfunction is a pathological feature of Duchenne muscular Dystrophy (DMD), a debilitating and fatal neuromuscular disorder characterised by progressive muscle wasting and weakness. Mitochondria are a source of cellular ATP and involved in Ca2+ regulation and apoptotic signalling. Ameliorating aberrant mitochondrial function has therapeutic potential for reducing DMD disease severity. The dystrophic mdx mouse exhibits peak muscle damage at 21-28d which stabilises after 8 weeks. The amino acid taurine is implicated in mitochondrial health and function, with endogenous concentrations low when measured during the cycle of peak muscle damage in mdx mice...
December 20, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29348263/phosphoinositide-3-kinase-gamma-inhibition-protects-from-anthracycline-cardiotoxicity-and-reduces-tumor-growth
#5
Mingchuan Li, Valentina Sala, Maria Chiara De Santis, James Cimino, Paola Cappello, Nicola Pianca, Anna Di Bona, Jean Piero Margaria, Miriam Martini, Edoardo Lazzarini, Flora Pirozzi, Luca Rossi, Irene Franco, Julia Bornbaum, Jacqueline Heger, Susanne Rohrbach, Alessia Perino, Carlo G Tocchetti, Braulio H F Lima, Mauro M Teixeira, Paolo E Porporato, Rainer Schulz, Annalisa Angelini, Marco Sandri, Pietro Ameri, Sebastiano Sciarretta, Roberto César P Lima-Júnior, Marco Mongillo, Tania Zaglia, Fulvio Morello, Francesco Novelli, Emilio Hirsch, Alessandra Ghigo
Background -Anthracyclines, such as doxorubicin (DOX), are potent anti-cancer agents for the treatment of solid tumors and hematological malignancies. However, their clinical use is hampered by cardiotoxicity. This study sought to investigate the role of PI3Kγ in DOX-induced cardiotoxicity and the potential cardio-protective and anti-cancer effects of PI3Kγ inhibition. Methods -Mice expressing a kinase-inactive PI3Kγ or receiving PI3Kγ selective inhibitors were subjected to chronic DOX treatment. Cardiac function was analyzed by echocardiography and DOX-mediated signaling was assessed in whole hearts or in isolated cardiomyocytes...
January 18, 2018: Circulation
https://www.readbyqxmd.com/read/29346561/floricolin-c-elicits-intracellular-ros-accumulation-and-disrupts-mitochondria-to-exert-fungicidal-action
#6
Ming Zhang, Wenqiang Chang, Hongzhuo Shi, Ying Li, Sha Zheng, Wei Li, Hongxiang Lou
Candida albicans, one most prevalent fungal pathogen, causes severe mucosal and invasive infections in predisposed individuals. The rise of fungal infection and drug-resistance demands the development of novel antifungal agents. In this study, we observed that floricolin C (FC), a p-terphenyl pigment from an endolichenic fungus, killed C. albicans cells at planktonic state or within biofilms through reactive oxygen species (ROS) accumulation. Further test revealed that FC could directly damage the mitochondria to cause ROS accumulation...
January 15, 2018: FEMS Yeast Research
https://www.readbyqxmd.com/read/29346115/mitochondrial-dysfunction-a-key-player-in-the-pathogenesis-of-cardiovascular-diseases-linked-to-air-pollution
#7
REVIEW
Sri Rahavi Boovarahan, Gino A Kurian
Air pollution has become an environmental burden with regard to non-communicable diseases, particularly heart disease. It has been reported that air pollution can accelerate the development of heart failure and atrial fibrillation. Air pollutants encompass various particulate matters (PMs), which change the blood composition and heart rate and eventually leads to cardiac failure by triggering atherosclerotic plaque ruptures or by developing irreversible ischemia. A series of major epidemiological and observational studies have established the noxious effect of air pollutants on cardiovascular diseases (CVD), but the underlying molecular mechanisms of its susceptibility and the pathological disease events remain largely elusive and are predicted to be initiated in the cell organelle...
January 18, 2018: Reviews on Environmental Health
https://www.readbyqxmd.com/read/29343514/trpm2-channel-mediated-regulation-of-autophagy-maintains-mitochondrial-function-and-promotes-gastric-cancer-cell-survival-via-the-jnk-signaling-pathway
#8
Shekoufeh Almasi, Barry E Kennedy, Mariam El Aghil, Andra M Sterea, Shashi Gujar, Santiago Partida-Sánchez, Yassine El Hiani
A lack of effective treatment is one of the main factors contributing to gastric cancer-related death. Discovering effective targets and understanding their underlying anticancer mechanism is key to achieving the best response to treatment and to limiting side effects. Although recent studies have shown that the cation channel transient receptor potential melastatin-2 (TRPM2) is crucial for cancer cell survival, the exact mechanism remains unclear, limiting its therapeutic potential. Here, using molecular and functional assays, we investigated the role of TRPM2 in survival of gastric cancer cells...
January 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29342113/mitochondria-oxidative-stress-and-the-kynurenine-system-with-a-focus-on-ageing-and-neuroprotection
#9
REVIEW
Katalin Sas, Elza Szabó, László Vécsei
In this review, the potential causes of ageing are discussed. We seek to gain insight into the main physiological functions of mitochondria and discuss alterations in their function and the genome, which are supposed to be the central mechanisms in senescence. We conclude by presenting the potential modulating role of the kynurenine pathway in the ageing processes. Mitochondrial dynamics are supposed to have important physiological roles in maintaining cell homeostasis. During ageing, a decrease in mitochondrial dynamics was reported, potentially compromising the function of mitochondria...
January 17, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29340048/alteration-of-mitochondrial-biogenesis-promotes-disease-progression-in-multiple-myeloma
#10
Xin Zhan, Wenjie Yu, Reinaldo Franqui-Machin, Melissa L Bates, Kalyan Nadiminti, Huojun Cao, Brad A Amendt, Yogesh Jethava, Ivana Frech, Fenghuang Zhan, Guido Tricot
Many cancers, including multiple myeloma (MM), retain more cytosolic iron to promote tumor cell growth and drug resistance. Higher cytosolic iron promotes oxidative damage due to its interaction with reactive oxygen species generated by mitochondria. The variation of mitochondrial biogenesis in different stages of MM disease was evaluated using gene expression profiles in a large clinical dataset. Sixteen of 18mitochondrial biogenesis related gene sets, including mitochondrial biogenesis signature and oxidative phosphorylation, were increased in myeloma cells compared with normal plasma cells and high expression was associated with an inferior patient outcome...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339192/tissue-specific-differences-in-mitochondrial-dna-maintenance-and-expression
#11
Elena Herbers, Nina J Kekäläinen, Anu Hangas, Jaakko L Pohjoismäki, Steffi Goffart
The different cell types of multicellular organisms have specialized physiological requirements, affecting also their mitochondrial energy production and metabolism. The genome of mitochondria is essential for mitochondrial oxidative phosphorylation (OXHPOS) and thus plays a central role in many human mitochondrial pathologies. Disorders affecting mitochondrial DNA (mtDNA) maintenance are typically resulting in a tissue-specific pattern of mtDNA deletions and rearrangements. Despite this role in disease as well as a biomarker of mitochondrial biogenesis, the tissue-specific parameters of mitochondrial DNA maintenance have been virtually unexplored...
January 12, 2018: Mitochondrion
https://www.readbyqxmd.com/read/29338042/a-pharmacological-screen-for-compounds-that-rescue-the-developmental-lethality-of-a-drosophila-atm-mutant
#12
Stacey A Rimkus, David A Wassarman
Ataxia-telangiectasia (A-T) is a neurodegenerative disease caused by mutation of the A-T mutated (ATM) gene. ATM encodes a protein kinase that is activated by DNA damage and phosphorylates many proteins, including those involved in DNA repair, cell cycle control, and apoptosis. Characteristic biological and molecular functions of ATM observed in mammals are conserved in Drosophila melanogaster. As an example, conditional loss-of-function ATM alleles in flies cause progressive neurodegeneration through activation of the innate immune response...
2018: PloS One
https://www.readbyqxmd.com/read/29336249/mutations-of-nuclear-and-mitochondrial-genomes-as-potential-targets-for-the-treatment-of-metabolic-syndrome
#13
Elena V Galitsyn, Andrey V Zhelankin, Igor A Sobenin, Alexander N Orekhov
In addition to external factors, such as exercise, food and the environment, genetic predisposition makes great contribution to the development of metabolic disorders and cardiovascular disease. This review is aimed to examine the genetic basis of complex metabolic disorders conventionally described as "metabolic syndrome" (MetS), with the special focus on currently known mutations in the nuclear and mitochondrial genomes, which are associated both with the individual components of MetS and combinations thereof, and also on the studies of the relationship of MetS phenotype as a binary trait...
January 15, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29336204/continuous-infusion-of-phenelzine-cyclosporine-a-or-the-combination-evaluation-of-mitochondrial-bioenergetics-oxidative-damage-and-cytoskeletal-degradation-following-severe-controlled-cortical-impact-traumatic-brain-injury-in-rats
#14
Jacqueline Renee Kulbe, Indrapal N Singh, Juan Wang, John E Cebak, Edward D Hall
To date, all monotherapy clinical traumatic brain injury (TBI) trials have failed, and there are currently no FDA-approved pharmacotherapies for the acute treatment of severe traumatic brain injury (TBI). Due to the complex secondary injury cascade following injury, there is a need to develop multi-mechanistic combinational neuroprotective approaches for the treatment of acute TBI. As central mediators of the TBI secondary injury cascade, both mitochondria and lipid peroxidation-derived aldehydes make promising therapeutic targets...
January 16, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29331828/a-recovery-time-after-warming-restores-mitochondrial-function-and-improves-developmental-competence-of-vitrified-ovine-oocytes
#15
Sara Succu, Sergio Domenico Gadau, Elisa Serra, Angelo Zinellu, Ciriaco Carru, Cristian Porcu, Salvatore Naitana, Fiammetta Berlinguer, Giovanni Giuseppe Leoni
The aim of the present study was to assess the ability of vitrified/warmed oocyte to recover from vitrification-induced damages after warming. In vitro matured, vitrified/warmed ovine oocytes were assessed for developmental competence, mitochondrial activity and distribution, ATP, ROS and catalase levels during 6 h of in vitro culture using fresh oocytes as control. ATP content in vitrified oocytes was lower than control during 4 h of post warming culture (p < .01). Vitrified oocytes were able to fill this gap only after 6 h of post-warming incubation...
December 26, 2017: Theriogenology
https://www.readbyqxmd.com/read/29331652/salinomycin-induces-primary-chicken-cardiomyocytes-death-via-mitochondria-mediated-apoptosis
#16
Xiuge Gao, Yani Zheng, Xiangchun Ruan, Hui Ji, Lin Peng, Dawei Guo, Shanxiang Jiang
Salinomycin, as a polyether ionophore antibiotic, is extensively used as a feed additive against coccidiosis in poultry and as a growth promoter of ruminants worldwide. Owing to its narrow therapeutic index, numerous intoxication have been reported in target/non-target animals by overdosage, misuse or drug interactions as well as human who consumed salinomycin accidently. Salinomycin-induced cardiotoxicity in chicken and non-target animals is considered as a major contributor to animal death. In the current study, we aim to elucidate the underlying mechanism of its myocardial toxicity using primary chicken myocardial cell as an in vitro model...
January 10, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29331649/friend-or-foe-reactive-oxygen-species-production-scavenging-and-signaling-in-plant-response-to-environmental-stresses
#17
Weronika Czarnocka, Stanisław Karpiński
In the natural environment, plants are exposed to a variety of biotic and abiotic stress conditions that trigger rapid changes in the production and scavenging of reactive oxygen species (ROS). The production and scavenging of ROS is compartmentalized, which means that, depending on stimuli type, they can be generated and eliminated in different cellular compartments such as the apoplast, plasma membrane, chloroplasts, mitochondria, peroxisomes, and endoplasmic reticulum. Although the accumulation of ROS is generally harmful to cells, ROS play an important role in signaling pathways that regulate acclimatory and defense responses in plants, such as systemic acquired acclimation (SAA) and systemic acquired resistance (SAR)...
January 10, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29331024/combination-therapy-of-lovastatin-and-ampk-activator-improves-mitochondrial-and-peroxisomal-functions-and-clinical-disease-in-eae-model
#18
Inderjit Singh, Devadoss J Samuvel, Seungho Choi, Nishant Saxena, Avtar K Singh, Jeseong Won
Recent studies report that loss and dysfunction of mitochondria and peroxisomes contribute to the myelin and axonal damage in multiple sclerosis (MS). In this study, we investigated the efficacy of lovastatin and AMPK activator (AICAR) combination on the loss and dysfunction of mitochondria and peroxisomes and myelin and axonal damage in the spinal cords, relative to the clinical disease symptoms, using a mouse model of experimental autoimmune encephalomyelitis (EAE, a model for MS). We observed that lovastatin and AICAR treatments individually provided partial protection of mitochondria/peroxisomes, myelin/axons, and thus partial attenuation of clinical disease in EAE mice...
January 13, 2018: Immunology
https://www.readbyqxmd.com/read/29328405/liraglutide-repairs-the-infarcted-heart-the-role-of-the-sirt1-parkin-mitophagy-pathway
#19
Huiying Qiao, Haiyan Ren, He Du, Minfang Zhang, Xiaofang Xiong, Rong Lv
Liraglutide is glucagon‑like peptide‑1 receptor agonist used for treating patients with type 2 diabetes mellitus. The present study aimed to investigate the role and mechanism of liraglutide in repairing the infarcted heart following myocardial infarction. The results of the present study demonstrated that amplification of the dose of liraglutide for ~28 days was able to reduce cardiac fibrosis, inflammatory responses and myocardial death in the post‑infarcted heart. In vitro, liraglutide protected cardiomyocyte mitochondria against the chronic hypoxic damage, inhibiting the mitochondrial apoptosis pathways...
January 2, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29325568/pink1-import-regulation-a-fine-system-to-convey-mitochondrial-stress-to-the-cytosol
#20
REVIEW
Shiori Sekine, Richard J Youle
Insights from inherited forms of parkinsonism suggest that insufficient mitophagy may be one etiology of the disease. PINK1/Parkin-dependent mitophagy, which helps maintain a healthy mitochondrial network, is initiated by activation of the PINK1 kinase specifically on damaged mitochondria. Recent investigation of this process reveals that import of PINK1 into mitochondria is regulated and yields a stress-sensing mechanism. In this review, we focus on the mechanisms of mitochondrial stress-dependent PINK1 activation that is exerted by regulated import of PINK1 into different mitochondrial compartments and how this offers strategies to pharmacologically activate the PINK1/Parkin pathway...
January 10, 2018: BMC Biology
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