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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/29128369/inhibition-of-poly-adp-ribose-polymerase-1-alters-expression-of-mitochondria-related-genes-in-pc12-cells-relevance-to-mitochondrial-homeostasis-in-neurodegenerative-disorders
#2
Grzegorz A Czapski, Magdalena Cieślik, Przemysław L Wencel, Sylwia Wójtowicz, Robert P Strosznajder, Joanna B Strosznajder
Alzheimer's disease (AD) is characterized by the release of amyloid beta peptides (Aβ) in the form of monomers/oligomers which may lead to oxidative stress, mitochondria dysfunction, synaptic loss, neuroinflammation and, in consequence, to overactivation of poly(ADP-ribose) polymerase-1 (PARP-1). However, Aβ peptides are also released in the brain ischemia, traumatic injury and in inflammatory response. PARP-1 is suggested to be a promising target in therapy of neurodegenerative disorders. We investigated the impact of PARP-1 inhibition on transcription of mitochondria-related genes in PC12 cells...
November 8, 2017: Biochimica et Biophysica Acta
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
#3
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/29107503/abrogating-mitochondrial-dynamics-in-mouse-hearts-accelerates-mitochondrial-senescence
#4
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/29097872/mitofusin-2-mediated-mitochondrial-ca-2-uptake-1-2-induced-liver-injury-in-rat-remote-ischemic-perconditioning-liver-transplantation-and-alpha-mouse-liver-12-hypoxia-cell-line-models
#5
Ruo-Peng Liang, Jun-Jun Jia, Jian-Hui Li, Ning He, Yan-Fei Zhou, Li Jiang, Tao Bai, Hai-Yang Xie, Lin Zhou, Yu-Ling Sun
AIM: To investigate the protective mechanism of mitofusin-2 (Mfn2) in rat remote ischemic perconditioning (RIC) models and revalidate it in alpha mouse liver-12 (AML-12) hypoxia cell lines. METHODS: Sprague-Dawley rats were divided into three groups (n = 6 each): sham, orthotopic liver transplantation and RIC. After operation, blood samples were collected to test alanine aminotransferase and aspartate aminotransferase. The liver lobes were harvested for histopathological examination, western blotting (WB) and quantitative real-time (qRT)-PCR...
October 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29074197/mitochondrial-dysfunction-perturbations-of-mitochondrial-dynamics-and-biogenesis-involved-in-endothelial-injury-induced-by-silica-nanoparticles
#6
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/29068134/structure-function-and-regulation-of-mitofusin-2-in-health-and-disease
#7
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/29040533/hippocampal-phosphorylated-tau-induced-cognitive-decline-dendritic-spine-loss-and-mitochondrial-abnormalities-in-a-mouse-model-of-alzheimer-s-disease
#8
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/29036319/discovery-of-susceptibility-loci-associated-with-tuberculosis-in-han-chinese
#9
Hui Qi, Yong-Biao Zhang, Lin Sun, Cheng Chen, Biao Xu, Fang Xu, Jia-Wen Liu, Jin-Cheng Liu, Chen Chen, Wei-Wei Jiao, Chen Shen, Jing Xiao, Jie-Qiong Li, Ya-Jie Guo, Yong-Hong Wang, Qin-Jing Li, Qing-Qin Yin, Ying-Jia Li, Ting Wang, Xing-Yun Wang, Ming-Liang Gu, Jun Yu, A-Dong Shen
Genome-wide association studies (GWASs) have revealed the worldwide heterogeneity of genetic factors in tuberculosis (TB) susceptibility. Despite having the third highest global TB burden, no TB-related GWAS has been performed in China. Here, we performed the first three-stage GWAS on TB in the Han Chinese population. In the stage 1 (discovery stage), after quality control, 691,388 SNPs present in 972 TB patients and 1,537 controls were retained. After replication on an additional 3,460 TB patients and 4,862 controls (stages 2 and 3), we identified three significant loci associated with TB, the most significant of which was rs4240897 (logistic regression P = 1...
September 26, 2017: Human Molecular Genetics
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
#10
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/28977005/renal-cold-storage-followed-by-transplantation-impairs-expression-of-key-mitochondrial-fission-and-fusion-proteins
#11
Nirmala Parajuli, Stephen Shrum, Julia Tobacyk, Alex Harb, John M Arthur, Lee Ann MacMillan-Crow
BACKGROUND: The majority of transplanted kidneys are procured from deceased donors which all require exposure to cold storage (CS) for successful transplantation. Unfortunately, this CS leads to renal and mitochondrial damage but, specific mitochondrial targets affected by CS remain largely unknown. The goal of this study is to determine whether pathways involved with mitochondrial fusion or fission, are disrupted during renal CS. METHODS: Male Lewis rat kidneys were exposed to cold storage (CS) alone or cold storage combined with transplantation (CS/Tx)...
2017: PloS One
https://www.readbyqxmd.com/read/28973648/the-nad-dependent-deacetylase-sirt2-attenuates-oxidative-stress-and-mitochondrial-dysfunction-and-improves-insulin-sensitivity-in-hepatocytes
#12
Vera Lemos, Rita M de Oliveira, Luana Naia, Éva Szegö, Elisabete Ramos, Sónia Pinho, Fernando Magro, Cláudia Cavadas, A Cristina Rego, Vítor Costa, Tiago F Outeiro, Pedro Gomes
Insulin resistance is a major predictor of the development of metabolic disorders. Sirtuins (SIRTs) have emerged as potential targets that can be manipulated to counteract age-related diseases, including type 2 diabetes. SIRT2 has been recently shown to exert important metabolic effects, but whether SIRT2 regulates insulin sensitivity in hepatocytes is currently unknown. The aim of this study is to investigate this possibility and to elucidate underlying molecular mechanisms. Here, we show that SIRT2 is downregulated in insulin-resistant hepatocytes and livers, and this was accompanied by increased generation of reactive oxygen species, activation of stress-sensitive ERK1/2 kinase, and mitochondrial dysfunction...
November 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28969390/mutations-in-dnm1l-as-in-opa1-result-indominant-optic-atrophy-despite-opposite-effectson-mitochondrial-fusion-and-fission
#13
Sylvie Gerber, Majida Charif, Arnaud Chevrollier, Tanguy Chaumette, Claire Angebault, Mariame Selma Kane, Aurélien Paris, Jennifer Alban, Mélanie Quiles, Cécile Delettre, Dominique Bonneau, Vincent Procaccio, Patrizia Amati-Bonneau, Pascal Reynier, Stéphanie Leruez, Raphael Calmon, Nathalie Boddaert, Benoit Funalot, Marlène Rio, Didier Bouccara, Isabelle Meunier, Hiromi Sesaki, Josseline Kaplan, Christian P Hamel, Jean-Michel Rozet, Guy Lenaers
Dominant optic atrophy is a blinding disease due to the degeneration of the retinal ganglion cells, the axons of which form the optic nerves. In most cases, the disease is caused by mutations in OPA1, a gene encoding a mitochondrial large GTPase involved in cristae structure and mitochondrial network fusion. Using exome sequencing, we identified dominant mutations in DNM1L on chromosome 12p11.21 in three large families with isolated optic atrophy, including the two families that defined the OPA5 locus on chromosome 19q12...
October 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28964889/modulating-mitochondrial-morphology-enhances-antitumor-effect-of-5-ala-mediated-photodynamic-therapy-both-in-vitro-and-in-vivo
#14
Hongyou Zhao, Rong Yin, Ying Wang, Yuan-Hao Lee, Ting Luo, Jiaying Zhang, Haixia Qiu, Stephen Ambrose, Lijie Wang, Jie Ren, Jie Yao, Defu Chen, Yucheng Wang, Zhipin Liang, Jie Zhen, Sumin Wu, Zulin Ye, Jing Zeng, Naiyan Huang, Ying Gu
5-aminolevulinic acid mediated PDT (5-ALA-PDT) is an approved therapeutic procedure for treating carcinomas of the cervix. However, when employed as a monotherapy, 5-ALA-PDT could not produce satisfactory results toward large and deep tumors. Therefore, developing a method to improve the efficacy of 5-ALA-PDT becomes important. In this study, we demonstrate an enhanced antitumor effect of 5-ALA-PDT by the modulation of mitochondrial morphology. The mitochondria in the cells were regulated into tubular mitochondria or fragmented mitochondria through over expression of Drp1 or Mfn2...
September 20, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28957766/the-inflammatory-responses-in-cu-mediated-elemental-imbalance-is-associated-with-mitochondrial-fission-and-intrinsic-apoptosis-in-gallus-gallus-heart
#15
Siwen Li, Hongjing Zhao, Yu Wang, Yizhi Shao, Jinglun Li, Juanjuan Liu, Mingwei Xing
Copper (Cu) is an essential trace element for organism of function properly. Overexposure to Cu causes chronic cardiac impairment. The aim of this study was to investigate the change of 28-trace element, inflammatory response, the possible mitochondrial dynamics and apoptosis under Cu exposure in the heart of chickens. Cupric sulfate (CuSO4) (300 mg/kg) was administered in a basal diet to male Hy-line chickens (one-day-old) for 90 days. Results showed the concentrations of Cu in the Cu group were increased by 57...
September 21, 2017: Chemosphere
https://www.readbyqxmd.com/read/28952074/mfn2-mediated-preservation-of-mitochondrial-function-contributes-to-the-protective-effects-of-bhapi-in-response-to-ischemia
#16
Xiao-Li Chen, Guo-Ping Zhang, Sheng-Long Guo, Jia-Qi Ding, Jia-Ji Lin, Qian Yang, Zhu-Yi Li
Disturbances in intracellular iron homeostasis are associated with neuronal injury after stroke. However, exposure of cells to classical chelators may interfere with physiological iron functions. BHAPI is an iron prochelator that exerts strong iron binding capacity only under oxidative stress conditions. This study investigated the protective effects of N'-(1-(2-((4-(4,4,5,5-tetramethyl-1,2,3-dioxoborolan-2-yl)benzyl)oxy)phenyl)ethylidene (BHAPI) on an in vitro ischemia model mimicked by oxygen and glucose deprivation (OGD) in neuronal HT22 cells...
September 26, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28944836/aberrant-promoter-methylation-of-multiple-genes-in-vsmc-proliferation-induced-by-hcy
#17
Sheng-Chao Ma, Jian-Cheng Cao, Hui-Ping Zhang, Yun Jiao, Hui Zhang, Yang-Yang He, Yan-Hua Wang, Xiao-Ling Yang, An-Ning Yang, Jue Tian, Ming-Hao Zhang, Xiao-Ming Yang, Guan-Jun Lu, Shao-Ju Jin, Yue-Xia Jia, Yi-Deng Jiang
Vascular smooth muscle cell (VSMC) proliferation is a primary pathological event in atherosclerosis (AS), and homocysteine (Hcy) is an independent risk factor for AS. However, the underlying mechanisms are still lagging. Studies have used the combination of methylation of promoters of multiple genes to diagnose tumors, thus the aim of the current study was to investigate the role of methylation status of several genes in VSMCs treated with Hcy. CpG islands were identified in the promoters of platelet‑derived growth factor (PDGF), p53, phosphatase and tensin homologue on chromosome 10 (PTEN) and mitofusin 2 (MFN2)...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28944094/the-arl2-gtpase-regulates-mitochondrial-fusion-from-the-intermembrane-space
#18
Laura E Newman, Cara R Schiavon, Rachel E Turn, Richard A Kahn
Mitochondria are essential, dynamic organelles that regularly undergo both fusion and fission in response to cellular conditions, though mechanisms of the regulation of their dynamics are incompletely understood. We provide evidence that increased activity of the small GTPase ARL2 is strongly correlated with an increase in fusion, while loss of ARL2 activity results in a decreased rate of mitochondrial fusion. Strikingly, expression of activated ARL2 can partially restore the loss of fusion resulting from deletion of either mitofusin 1 (MFN1) or mitofusin 2 (MFN2), but not deletion of both...
2017: Cellular Logistics
https://www.readbyqxmd.com/read/28940366/lon-protease-a-novel-mitochondrial-matrix-protein-in-the-interconnection-between-drug-induced-mitochondrial-dysfunction-and-er-stress
#19
Miriam Polo, Fernando Alegre, Angela B Moragrega, Lara Gibellini, Alberto Marti-Rodrigo, Ana Blas-Garcia, Juan V Esplugues, Nadezda Apostolova
BACKGROUND AND PURPOSE: Mitochondria-associated membranes (MAMs) are specific ER-domains that enable direct interaction with mitochondria and mediate metabolic flow and Ca(2+) transfer. A growing list of proteins have been identified as MAMs components, but how they are recruited and function during complex cell stress situations is still not understood while the participation of mitochondrial matrix proteins is largely undervalued. EXPERIMENTAL APPROACH: This work compares mitochondrial/ER contact during combined ER stress/mitochondrial dysfunction using a model of human hepatoma cells (Hep3B cell line) treated for 24h with classic pharmacological inducers of ER stress (thapsigargin), mitochondrial dysfunction (CCCP or rotenone) or both (the antiretroviral drug Efavirenz used at clinically relevant concentrations)...
September 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28904083/assessing-the-effects-of-mitofusin-2-deficiency-in-the-adult-heart-using-3d-electron-tomography
#20
Siavash Beikoghli Kalkhoran, Andrew R Hall, Ian J White, Jackie Cooper, Qiao Fan, Sang-Bing Ong, Sauri Hernández-Reséndiz, Hector Cabrera-Fuentes, Kroekkiat Chinda, Bibhas Chakraborty, Gerald W Dorn, Derek M Yellon, Derek J Hausenloy
The effects of mitofusin 2 (MFN2) deficiency, on mitochondrial morphology and the mitochondria-junctional sarcoplasmic reticulum (jSR) complex in the adult heart, have been previously investigated using 2D electron microscopy, an approach which is unable to provide a 3D spatial assessment of these imaging parameters. Here, we use 3D electron tomography to show that MFN2-deficient mitochondria are larger in volume, more elongated, and less rounded; have fewer mitochondria-jSR contacts, and an increase in the distance between mitochondria and jSR, when compared to WT mitochondria...
September 2017: Physiological Reports
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