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https://www.readbyqxmd.com/read/29144987/benzo-a-pyren-7-8-dihydrodiol-9-10-epoxide-induces-human-trophoblast-swan-71-cell-dysfunctions-due-to-cell-apoptosis-through-disorder-of-mitochondrial-fission-fusion
#1
Weiping Wang, Rong Wang, Qiao Zhang, Gil Mor, Huidong Zhang
Benzo(a)pyren-7,8-dihydrodiol-9,10-epoxide (BPDE) is an endocrine disrupter and ultimate carcinogenic product of benzo(a)pyrene (BaP). Numerous studies have shown that BPDE causes trophoblast-related diseases, such as preeclampsia, growth restriction or miscarriages. However, the underlying mechanism, especially the mitochondria-related BPDE-induced trophoblast dysfunction remains unknown. In this study, we examined mitochondrial functions in BPDE-induced human trophoblast cell line Swan 71. BPDE decreased cell ability, attenuated cell invasion and HCG secretion, induced cell apoptosis, decreased mitochondrial membrane potential, increased reactive oxygen species (ROS) and MDA, and decreased SOD activity in a dose-dependent manner...
November 13, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29142025/cardioprotection-of-dapagliflozin-and-vildagliptin-in-cardiac-reperfusion-injury-rats
#2
Pongpan Tanajak, Piangkwan Sa-Nguanmoo, Sivaporn Sivasinprasan, Savitree Thummasorn, Natthaphat Siri-Angkul, Siriporn Chattipakorn, Nipon Chattipakorn
Sodium-glucose cotransporter 2 inhibitor (SGLT2-i) effects on cardiac ischemia/reperfusion (I/R) injury are unclear. Unlike SGLT2-i, dipeptidyl peptidase 4 inhibitors (DPP4-i) have shown effective cardioprotection in cardiac I/R injury. We aimed to investigate whether SGLT2-i reduces myocardial dysfunction and myocardial injury to a greater extent than DPP4-i in obese-insulin resistant rats with/without cardiac I/R injury. The high fat (HF) diet induced obese-insulin resistant rats were divided into 4 groups and received the following treatments for 28 days: vehicle (HFV); vildagliptin at a dosage of 3 mg/kg/day (HFVil); dapagliflozin at a dosage of 1 mg/kg/day (HFDa); and combination drugs (HFDaVil)...
November 15, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/29142021/inf2-mediated-actin-polymerization-at-the-er-stimulates-mitochondrial-calcium-uptake-inner-membrane-constriction-and-division
#3
Rajarshi Chakrabarti, Wei-Ke Ji, Radu V Stan, Jaime de Juan Sanz, Timothy A Ryan, Henry N Higgs
Mitochondrial division requires division of both the inner and outer mitochondrial membranes (IMM and OMM, respectively). Interaction with endoplasmic reticulum (ER) promotes OMM division by recruitment of the dynamin Drp1, but effects on IMM division are not well characterized. We previously showed that actin polymerization through ER-bound inverted formin 2 (INF2) stimulates Drp1 recruitment in mammalian cells. Here, we show that INF2-mediated actin polymerization stimulates a second mitochondrial response independent of Drp1: a rise in mitochondrial matrix calcium through the mitochondrial calcium uniporter...
November 15, 2017: Journal of Cell Biology
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/29113360/microrna-488-inhibits-chemoresistance-of-ovarian-cancer-cells-by-targeting-six1-and-mitochondrial-function
#5
Zhuo Yang, ZiYi Feng, JiaHui Gu, XinHui Li, QianZhe Dong, KuiRan Liu, Yan Li, Ling OuYang
Dysregulation of miR-488 has been implicated in several human cancers. In this study, we aim to explore its expression and biological function in ovarian cancers. We found miR-488 expression was downregulated in ovarian cancer tissues. Using CCK8 and colony formation assay showed that miR-488 inhibited SKOV3 cell proliferation and colony formation, with downregulation of cyclin D1 and cyclin E protein. While miR-488 inhibitor promoted OVCAR3 cell growth and colony formation. Cell viability and Annexin V/PI staining showed that miR-488 downregulated cell survival and increased apoptosis rate when treated with cisplatin and paclitaxel...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29107503/abrogating-mitochondrial-dynamics-in-mouse-hearts-accelerates-mitochondrial-senescence
#6
Moshi Song, Antonietta Franco, Julie A Fleischer, Lihong Zhang, Gerald W Dorn
Mitochondrial fusion and fission are critical to heart health; genetically interrupting either is rapidly lethal. To understand whether it is loss of, or the imbalance between, fusion and fission that underlies observed cardiac phenotypes, we engineered mice in which Mfn-mediated fusion and Drp1-mediated fission could be concomitantly abolished. Compared to fusion-defective Mfn1/Mfn2 cardiac knockout or fission-defective Drp1 cardiac knockout mice, Mfn1/Mfn2/Drp1 cardiac triple-knockout mice survived longer and manifested a unique pathological form of cardiac hypertrophy...
October 21, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/29107300/adult-neural-stem-cell-fate-is-determined-by-thyroid-hormone-activation-of-mitochondrial-metabolism
#7
J D Gothié, A Sébillot, C Luongo, M Legendre, C Nguyen Van, K Le Blay, M Perret-Jeanneret, S Remaud, B A Demeneix
OBJECTIVE: In the adult brain, neural stem cells (NSCs) located in the subventricular zone (SVZ) produce both neuronal and glial cells. Thyroid hormones (THs) regulate adult NSC differentiation towards a neuronal phenotype, but also have major roles in mitochondrial metabolism. As NSC metabolism relies mainly on glycolysis, whereas mature cells preferentially use oxidative phosphorylation, we studied how THs and mitochondrial metabolism interact on NSC fate determination. METHODS: We used a mitochondrial membrane potential marker in vivo to analyze mitochondrial activity in the different cell types in the SVZ of euthyroid and hypothyroid mice...
November 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29097020/skeletal-muscle-autophagy-and-mitophagy-in-endurance-trained-runners-before-and-after-a-high-fat-meal
#8
Michael D Tarpey, Kevin P Davy, Ryan P McMillan, Suzanne M Bowser, Tanya M Halliday, Nabil E Boutagy, Brenda M Davy, Madlyn I Frisard, Matthew W Hulver
OBJECTIVE: We tested the hypothesis that skeletal muscle of endurance-trained male runners would exhibit elevated autophagy and mitophagy markers, which would be associated with greater metabolic flexibility following a high-fat meal (HFM). METHODS: Muscle biopsies were collected to determine differences in autophagy and mitophagy protein markers and metabolic flexibility under fasting conditions and 4 h following a HFM between endurance-trained male runners (n = 10) and sedentary, non-obese controls (n = 9)...
October 21, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29092894/mitochondrial-reactive-oxygen-species-in-lipotoxic-hearts-induces-post-translational-modifications-of-akap121-drp1-and-opa1-that-promote-mitochondrial-fission
#9
Kensuke Tsushima, Heiko Bugger, Adam R Wende, Jamie Soto, Gregory A Jenson, Austin R Tor, Rose McGlauflin, Helena C Kenny, Yuan Zhang, Rhonda Souvenir, Xiao X Hu, Crystal L Black, Renata O Pereira, Vitor A Lira, Kenneth Spitzer, Terry L Sharp, Kooresh I Shoghi, Genevieve C Sparagna, Eva A Rog-Zielinska, Peter Kohl, Oleh Khalimonchuk, Jean E Schaffer, E Dale Abel
Rationale: Cardiac lipotoxicity, characterized by increased uptake, oxidation and accumulation of lipid intermediates, contributes to cardiac dysfunction in obesity and diabetes. However, mechanisms linking lipid overload and mitochondrial dysfunction are incompletely understood. Objective: To elucidate the mechanisms for mitochondrial adaptations to lipid overload in postnatal hearts in vivo. Methods and Results: Using a transgenic mouse model of cardiac lipotoxicity overexpressing long-chain acyl-CoA synthetase 1 in cardiomyocytes, we show that modestly increased myocardial fatty acid uptake leads to mitochondrial structural remodeling with significant reduction in minimum diameter...
November 1, 2017: Circulation Research
https://www.readbyqxmd.com/read/29074197/mitochondrial-dysfunction-perturbations-of-mitochondrial-dynamics-and-biogenesis-involved-in-endothelial-injury-induced-by-silica-nanoparticles
#10
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/29072687/guanylate-binding-protein-2-regulates-drp1-mediated-mitochondrial-fission-to-suppress-breast-cancer-cell-invasion
#11
Juan Zhang, Yu Zhang, Wenshuang Wu, Fang Wang, Xinyu Liu, Guanghou Shui, Chunlai Nie
Guanylate-binding protein 2 (GBP2) is a member of the large GTPase superfamily that is strongly induced by interferon-γ (IFN-γ). Although the biochemical characteristics of GBP2 have been reported in detail, its biological function has not been thoroughly elucidated to date. To the best of our knowledge, this study presents the first demonstration that GBP2 inhibits mitochondrial fission and cell metastasis in breast cancer cells both in vitro and in vivo. Our previous work demonstrated that dynamin-related protein 1 (Drp1)-dependent mitochondrial fission has a key role in breast cancer cell invasion...
October 26, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29068134/structure-function-and-regulation-of-mitofusin-2-in-health-and-disease
#12
Gursimran Chandhok, Michael Lazarou, Brent Neumann
Mitochondria are highly dynamic organelles that constantly migrate, fuse, and divide to regulate their shape, size, number, and bioenergetic function. Mitofusins (Mfn1/2), optic atrophy 1 (OPA1), and dynamin-related protein 1 (Drp1), are key regulators of mitochondrial fusion and fission. Mutations in these molecules are associated with severe neurodegenerative and non-neurological diseases pointing to the importance of functional mitochondrial dynamics in normal cell physiology. In recent years, significant progress has been made in our understanding of mitochondrial dynamics, which has raised interest in defining the physiological roles of key regulators of fusion and fission and led to the identification of additional functions of Mfn2 in mitochondrial metabolism, cell signalling, and apoptosis...
October 25, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/29054984/overcoming-resistance-to-cetuximab-with-honokiol-a-small-molecule-polyphenol
#13
Hannah E Pearson, Mari Iida, Rachel A Orbuch, Nellie K McDaniel, Kwangok P Nickel, Randall J Kimple, Jack Arbiser, Deric L Wheeler
Overexpression and activation of the Epidermal Growth Factor Receptor (EGFR) have been linked to poor prognosis in several human cancers. Cetuximab is a monoclonal antibody against EGFR, that is used for the treatment in head and neck squamous cell carcinoma (HNSCC) and metastatic colorectal cancer. Unfortunately, most tumors have intrinsic or acquire resistance to cetuximab during the course of therapy. Honokiol is a natural compound found in the bark and leaves of the Chinese Magnolia tree and is established to have several anti-cancer properties without appreciable toxicity...
October 20, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29054138/mdivi-1-protects-human-w8b2-cardiac-stem-cells-from-oxidative-stress-and-simulated-ischemia-reperfusion-injury
#14
Ayeshah A Rosdah, Simon T Bond, Priyadharshini Sivakumaran, Ashfaqul Hoque, Jonathan S Oakhill, Brian G Drew, Lea Md Delbridge, Shiang Yong Lim
Cardiac stem cell (CSC) therapy is a promising approach to treat ischemic heart disease. However, the poor survival of transplanted stem cells in the ischemic myocardium has been a major impediment in achieving an effective cell-based therapy against myocardial infarction. Inhibiting mitochondrial fission has been shown to promote survival of several cell types. However, the role of mitochondrial morphology in survival of human CSC remains unknown. In this study, we investigated whether Mdivi-1, an inhibitor of mitochondrial fission protein Drp1, can improve survival of a novel population of human W8B2+ CSCs in hydrogen peroxide-induced oxidative stress and simulated ischemia-reperfusion injury models...
October 20, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/29040533/hippocampal-phosphorylated-tau-induced-cognitive-decline-dendritic-spine-loss-and-mitochondrial-abnormalities-in-a-mouse-model-of-alzheimer-s-disease
#15
Ramesh Kandimalla, Maria Manczak, Xiangling Yin, Rui Wang, P Hemachandra Reddy
The purpose of our study was to understand the toxic effects of hippocampal phosphorylated tau in tau mice. Using rotarod and Morris Water Maze tests, immunoblotting & immunofluorescence, Golgi-cox staining and transmission electron microscopy, we assessed cognitive behavior, measured protein levels of mitochondrial dynamics, MAP2, total & phosphorylated tau, and quantified dendritic spines and mitochondrial number and length in 12-month-old tau mice with P301L mutation. Mitochondrial function was assessed by measuring the levels of H2O2, lipid peroxidation, cytochrome oxidase activity and mitochondrial ATP...
October 12, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29038583/zdhhc13-dependent-drp1-s-palmitoylation-impacts-brain-bioenergetics-anxiety-coordination-and-motor-skills
#16
Eleonora Napoli, Gyu Song, Siming Liu, Alexsandra Espejo, Carlos J Perez, Fernando Benavides, Cecilia Giulivi
Protein S-palmitoylation is a reversible post-translational modification mediated by palmitoyl acyltransferase enzymes, a group of Zn(2+)-finger DHHC-domain-containing proteins (ZDHHC). Here, for the first time, we show that Zdhhc13 plays a key role in anxiety-related behaviors and motor function, as well as brain bioenergetics, in a mouse model (luc) carrying a spontaneous Zdhhc13 recessive mutation. At 3 m of age, mutant mice displayed increased sensorimotor gating, anxiety, hypoactivity, and decreased motor coordination, compared to littermate controls...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29030231/als-associated-mutation-sod1-g93a-leads-to-abnormal-mitochondrial-dynamics-in-osteocytes
#17
Huan Wang, Jianxun Yi, Xuejun Li, Yajuan Xiao, Kamal Dhakal, Jingsong Zhou
While the death of motor neuron is a pathological hallmark of amyotrophic lateral sclerosis (ALS), defects in other cell types or organs may also actively contribute to ALS disease progression. ALS patients experience progressive skeletal muscle wasting that may not only exacerbate neuronal degeneration, but likely has a significant impact on bone function. In our previous published study, we have discovered severe bone loss in an ALS mouse model with overexpression of ALS-associated mutation SOD1(G93A) (G93A)...
October 10, 2017: Bone
https://www.readbyqxmd.com/read/29028772/heme-oxygenase-1-protects-the-liver-from-septic-injury-by-modulating-tlr4-mediated-mitochondrial-quality-control-in-mice
#18
Jin-Sook Park, Hyo-Sun Choi, So-Yeon Yim, Sun-Mee Lee
Mitochondrial dysfunction is involved in the pathogenesis of sepsis-induced multiple organ dysfunction syndrome (MODS). Mitochondrial quality control (QC) is characterized by self-recovering mitochondrial damage through mitochondrial biogenesis, mitophagy, and fission/fusion. Heme oxygenase (HO)-1 acts as a signaling molecule to modulate inflammation. The present study elucidated the cytoprotective mechanisms of HO-1 in sepsis, particularly focusing on toll-like receptor (TLR)4-mediated mitochondrial QC. Mice were subjected to sepsis by cecal ligation and puncture (CLP)...
October 12, 2017: Shock
https://www.readbyqxmd.com/read/29026190/growth-hormone-secretagogues-hexarelin-and-jmv2894-protect-skeletal-muscle-from-mitochondrial-damages-in-a-rat-model-of-cisplatin-induced-cachexia
#19
Giuseppe Sirago, Elena Conte, Flavio Fracasso, Antonella Cormio, Jean-Alain Fehrentz, Jean Martinez, Clara Musicco, Giulia Maria Camerino, Adriano Fonzino, Laura Rizzi, Antonio Torsello, Angela Maria Serena Lezza, Antonella Liantonio, Palmiro Cantatore, Vito Pesce
Chemotherapy can cause cachexia, which consists of weight loss associated with muscle atrophy. The exact mechanisms underlying this skeletal muscle toxicity are largely unknown and co-therapies to attenuate chemotherapy-induced side effects are lacking. By using a rat model of cisplatin-induced cachexia, we here characterized the mitochondrial homeostasis in tibialis anterior cachectic muscle and evaluated the potential beneficial effects of the growth hormone secretagogues (GHS) hexarelin and JMV2894 in this setting...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29024001/dynamin-related-protein-1-mediated-mitochondrial-fission-contributes-to-post-traumatic-cardiac-dysfunction-in-rats-and-the-protective-effect-of-melatonin
#20
Mingge Ding, Jiao Ning, Na Feng, Zeyang Li, Zhenhua Liu, Yuanbo Wang, Yueming Wang, Xing Li, Cong Huo, Xin Jia, Rong Xu, Feng Fu, Xiaoming Wang, Jianming Pei
Mechanical trauma (MT) causes myocardial injury and cardiac dysfunction. However, the underlying mechanism remains largely unclear. This study investigated the role of mitochondrial dynamics in post-traumatic cardiac dysfunction and the protective effects of melatonin. Adult male Sprague Dawley rats were subjected to 5-minute rotations (200 revolutions at a rate of 40 rpm) to induce MT model. Melatonin was administrated intraperitoneally 5 minute after MT. Mitochondrial morphology, myocardial injury, and cardiac function were determined in vivo...
October 11, 2017: Journal of Pineal Research
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