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https://www.readbyqxmd.com/read/28191022/effect-of-mahuang-gancao-ganjiang-decoction-on-fusion-and-fission-of-mitochondria-and-apoptosis-of-lymphocytes-in-mice-under-cold-stress
#1
Longyun Chen, Huimin Chen
Mahuang Gancao Ganjiang Decoction (MGGD) can effectively alleviate the symptoms of the patients suffering from exogenous cold stress. However, the curative mechanism has not been fully clarified. This study was designed to investigate the effect of MGGD on the apoptosis of lymphocytes induced by cold stress in mice. The model mice were randomly divided into four groups: the normal control group (no handling mice), cold stress group, MGGD + cold stress group, and MGGD group. Lymphocytes of the mice were isolated from the peripheral blood...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28177702/modulation-of-mitochondrial-biomarkers-by-intermittent-hypobaric-hypoxia-and-aerobic-exercise-after-eccentric-exercise-in-trained-rats
#2
David Rizo-Roca, Juan Gabriel Ríos-Kristjánsson, Cristian Núñez-Espinosa, Estela Santos-Alves, José Magalhães, António Ascensão, Teresa Pagès, Ginés Viscor, Joan Ramon Torrella
Unaccustomed eccentric contractions induce muscle damage, calcium homeostasis disruption and mitochondrial alterations. Since exercise and hypoxia are known to modulate mitochondrial function, we aimed to analyze the effects on eccentric exercise-induced muscle damage (EEIMD), in trained rats, of two recovery protocols based on: 1) intermittent hypobaric hypoxia (IHH) and 2) IHH followed by exercise. The expression of biomarkers related to mitochondrial biogenesis, dynamics, oxidative stress and bioenergetics was evaluated...
February 2, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28176801/mfn2-suppresses-cancer-progression-through-inhibition-of-mtorc2-akt-signaling
#3
Ke Xu, Guo Chen, Xiaobo Li, Xiaoqin Wu, Zhijie Chang, Jianhua Xu, Yu Zhu, Peihao Yin, Xin Liang, Lei Dong
The mitochondrial GTPase mitofusin-2 (MFN2) has previously been reported to play a role in regulating cell proliferation, apoptosis and differentiation in a number of cell types. Here, we report that breast cancer patients with low MFN2 expression are associated with poor prognosis as compared to patients with high MFN2 expression. We find that MFN2 knockout from MCF7 and A549 cells via Crispr/Cas9 greatly promotes cell viability, colony formation, and invasion of cancer cells in vitro and in vivo, which were confirmed by colony formation assay, transwell invasion assay, and tumor xenograft model...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28164383/physiological-biochemical-anthropometric-and-biomechanical-influences-on-exercise-economy-in-humans
#4
Carsten Lundby, David Montero, Saskia Gehrig, Ulrika Anderson Hall, Pascal Kaiser, Robert Boushel, Anne-Kristine Meinild Lundby, Niels Kirk, Paola Valdivieso, Martin Flück, Niels H Secher, Frederik Edin, Tobias Hein, Klavs Madsen
Inter-individual variation in running and cycling exercise economy (EE) remains unexplained although studied for more than a century. This study is the first to comprehensively evaluate the importance of biochemical, structural, physiological, anthropometric, and biomechanical influences on running and cycling EE within a single study. In 22 healthy males (VO2 max range 45.5 to 72.1 ml.min(-1) .kg(-1) ) no factor related to skeletal muscle structure (% slow twitch fibre content, number of capillaries per fibre), mitochondrial properties (volume density, oxidative capacity, or mitochondrial efficiency) or protein content (UCP3 and MFN2 expression) explained variation in cycling and running EE among subjects...
February 5, 2017: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/28131082/mitochondrial-dynamics-in-type-2-diabetes-pathophysiological-implications
#5
REVIEW
Susana Rovira-Llopis, Celia Bañuls, Noelia Diaz-Morales, Antonio Hernandez-Mijares, Milagros Rocha, Victor M Victor
Mitochondria play a key role in maintaining cellular metabolic homeostasis. These organelles have a high plasticity and are involved in dynamic processes such as mitochondrial fusion and fission, mitophagy and mitochondrial biogenesis. Type 2 diabetes is characterised by mitochondrial dysfunction, high production of reactive oxygen species (ROS) and low levels of ATP. Mitochondrial fusion is modulated by different proteins, including mitofusin-1 (MFN1), mitofusin-2 (MFN2) and optic atrophy (OPA-1), while fission is controlled by mitochondrial fission 1 (FIS1), dynamin-related protein 1 (DRP1) and mitochondrial fission factor (MFF)...
January 16, 2017: Redox Biology
https://www.readbyqxmd.com/read/28110471/depletion-of-mitofusin-2-causes-mitochondrial-damage-in-cisplatin-induced-neuropathy
#6
Ilja Bobylev, Abhijeet R Joshi, Mohammed Barham, Wolfram F Neiss, Helmar C Lehmann
Sensory neuropathy is a relevant side effect of the antineoplastic agent cisplatin. Mitochondrial damage is assumed to play a critical role in cisplatin-induced peripheral neuropathy, but the pathomechanisms underlying cisplatin-induced mitotoxicity and neurodegeneration are incompletely understood. In an animal model of cisplatin-induced neuropathy, we determined in detail the extent and spatial distribution of mitochondrial damage during cisplatin treatment. Changes in the total number of axonal mitochondria during cisplatin treatment were assessed in intercostal nerves from transgenic mice that express cyan fluorescent protein...
January 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28108329/exercise-increases-mitochondrial-complex-i-activity-and-drp1-expression-in-the-brains-of-aged-mice
#7
Aaron M Gusdon, Jason Callio, Giovanna Distefano, Robert M O'Doherty, Bret H Goodpaster, Paul M Coen, Charleen T Chu
Exercise is known to have numerous beneficial effects. Recent studies indicate that exercise improves mitochondrial energetics not only in skeletal muscle but also in other tissues. While exercise elicits positive effects on memory, neurogenesis, and synaptic plasticity, the effects of exercise on brain mitochondrial energetics remain relatively unknown. Herein, we studied the effects of exercise training in old and young mice on brain mitochondrial energetics, in comparison to known effects on peripheral tissues that utilize fatty acid oxidation...
January 18, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28096879/association-between-mitofusin-2-gene-polymorphisms-and-late-onset-alzheimer-s-disease-in-the-korean-population
#8
Young Jong Kim, Jin Kyung Park, Won Sub Kang, Su Kang Kim, Changsu Han, Hae Ri Na, Hae Jeong Park, Jong Woo Kim, Young Youl Kim, Moon Ho Park, Jong-Woo Paik
OBJECTIVE: Mitochondrial dysfunction is a prominent and early feature of Alzheimer's disease (AD). The morphologic changes observed in the AD brain could be caused by a failure of mitochondrial fusion mechanisms. The aim of this study was to investigate whether genetic polymorphisms of two genes involved in mitochondrial fusion mechanisms, optic atrophy 1 (OPA1) and mitofusin 2 (MFN2), were associated with AD in the Korean population by analyzing genotypes and allele frequencies. METHODS: One coding single nucleotide polymorphism (SNP) in the MFN2, rs1042837, and two coding SNPs in the OPA1, rs7624750 and rs9851685, were compared between 165 patients with AD (83 men and 82 women, mean age 72...
January 2017: Psychiatry Investigation
https://www.readbyqxmd.com/read/28076385/the-effect-of-a-novel-c-820c-t-arg274trp-mutation-in-the-mitofusin-2-gene-on-fibroblast-metabolism-and-clinical-manifestation-in-a-patient
#9
Małgorzata Beręsewicz, Anna Boratyńska-Jasińska, Łukasz Charzewski, Maria Kawalec, Dagmara Kabzińska, Andrzej Kochański, Krystiana A Krzyśko, Barbara Zabłocka
Charcot-Marie-Tooth disease type 2A (CMT2A) is an autosomal dominant axonal peripheral neuropathy caused by mutations in the mitofusin 2 gene (MFN2). Mitofusin 2 is a GTPase protein present in the outer mitochondrial membrane and responsible for regulation of mitochondrial network architecture via the fusion of mitochondria. As that fusion process is known to be strongly dependent on the GTPase activity of mitofusin 2, it is postulated that the MFN2 mutation within the GTPase domain may lead to impaired GTPase activity, and in turn to mitochondrial dysfunction...
2017: PloS One
https://www.readbyqxmd.com/read/28076382/deregulated-expression-of-mitochondrial-proteins-mfn2-and-bcnl3l-in-placentae-from-sheep-somatic-cell-nuclear-transfer-scnt-conceptuses
#10
Marta Czernik, Paola Toschi, Federica Zacchini, Domenico Iuso, Grażyna Ewa Ptak
In various animal species, the main cause of pregnancy loss in conceptuses obtained by somatic cell nuclear transfer (SCNT) are placental abnormalities. Most abnormalities described in SCNT pregnancies (such as placentomegaly, reduced vascularisation, hypoplasia of trophoblastic epithelium) suggest that placental cell degeneration may be triggered by mitochondrial failure. We hypothesized that placental abnormalities of clones obtained by SCNT are related to mitochondrial dysfunction. To test this, early SCNT and control (CTR, from pregnancies obtained by in vitro fertilization) placentae were collected from pregnant ewes (at day 20 and 22 of gestation) and subjected to morphological, mRNA and protein analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28063088/mosaicism-for-a-pathogenic-mfn2-mutation-causes-minimal-clinical-features-of-cmt2a-in-the-parent-of-a-severely-affected-child
#11
Katherine Schon, Olivera Spasic-Boskovic, Kim Brugger, Tracey D Graves, Stephen Abbs, Soo-Mi Park, Gautam Ambegaonkar, Ruth Armstrong
Charcot-Marie-Tooth disease (CMT) refers to a genetically heterogeneous group of disorders which cause a peripheral motor and sensory neuropathy. The overall prevalence is 1 in 2500 individuals. Mutations in the MFN2 gene are the commonest cause for the axonal (CMT2) type. We describe a Caucasian 5-year old girl affected by CMT2A since the age of 2 years. She presented with unsteady gait, in-turning of the feet and progressive foot deformities. Nerve conduction studies suggested an axonal neuropathy and molecular testing identified a previously reported pathogenic variant c...
January 2017: Neurogenetics
https://www.readbyqxmd.com/read/28057766/rapid-degradation-of-mutant-slc25a46-by-the-ubiquitin-proteasome-system-results-in-mfn1-2-mediated-hyperfusion-of-mitochondria
#12
Janos Steffen, Ajay A Vashisht, Jijun Wan, Joanna C Jen, Steven M Claypool, James A Wohlschlegel, Carla M Koehler
SCL25A46 is a member of the mitochondrial carrier protein that surprisingly localizes to the outer membrane and is distantly related to Ugo1. Here we show that a subset of SLC25A46 interacted with mitochondrial dynamics components and the MICOS complex. Decreased expression of SLC25A46 resulted in increased stability and oligomerization of MFN1 and MFN2 on mitochondria, promoting mitochondrial hyperfusion. A mutation at L341P caused rapid degradation of SLC25A46 that manifested as a rare disease, pontocerebellar hypoplasia...
January 5, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28053050/parkin-functionally-interacts-with-pgc-1%C3%AE-to-preserve-mitochondria-and-protect-dopaminergic-neurons
#13
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/28013092/overexpression-of-mitofusin2-decreased-the-reactive-astrocytes-proliferation-in-vitro-induced-by-oxygen-glucose-deprivation-reoxygenation
#14
Yulong Shi, Chengla Yi, Xiao Li, Jiangpeng Wang, Fangyuan Zhou, Xiaoqian Chen
Glia scar is a hallmark in late-stage of brain stroke disease, which hinder axonal regeneration and neuronal repair. Mitofusin2 (Mfn2) is a newly found cellular proliferation inhibitor. This study is to elucidate the role of Mfn2 in reactive astrocytes induced by oxygen-glucose deprivation/reoxygenation(OGD/R) model in vitro. Up-expression in EdU staining and protein level of GFAP, PCNA and CyclinD1, demonstrates the distinct activation and proliferation of astrocytes after the stimulation of OGD/R. Meanwhile, Mfn2 was proved to be down-regulated both in gene and protein levels...
February 3, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/27997345/mitofusin-2-attenuates-the-histone-acetylation-at-collagen-iv-promoter-in-diabetic-nephropathy
#15
Xuhua Mi, Wanxin Tang, Xiaolei Chen, Fei Liu, Xiaohong Tang
Extracellular matrix (ECM) increase in diabetic nephropathy (DN) is closely related to mitochondrial dysfunction. The mechanism of protective function of mitofusin 2 (Mfn2) for mitochondria remains largely unknown. In this study, the molecular mechanisms for the effect of Mfn2 on mitochondria and subsequent collagen IV expression in DN were investigated. Ras-binding-deficient mitofusin 2 (Mfn2-Ras(Δ)) were overexpressed in rat glomerular mesangial cells, and then the cells were detected for mitochondrial morphology, cellular reactive oxygen species (ROS), mRNA and protein expression of collagen IV with advanced glycation end-product (AGE) stimulation...
November 2016: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/27907123/mice-hemizygous-for-a-pathogenic-mitofusin-2-allele-exhibit-hind-limb-foot-gait-deficits-and-phenotypic-perturbations-in-nerve-and-muscle
#16
Peter Bannerman, Travis Burns, Jie Xu, Laird Miers, David Pleasure
Charcot-Marie-Tooth disease type 2A (CMT2A), the most common axonal form of hereditary sensory motor neuropathy, is caused by mutations of mitofusin-2 (MFN2). Mitofusin-2 is a GTPase required for fusion of mitochondrial outer membranes, repair of damaged mitochondria, efficient mitochondrial energetics, regulation of mitochondrial-endoplasmic reticulum calcium coupling and axonal transport of mitochondria. We knocked T105M MFN2 preceded by a loxP-flanked STOP sequence into the mouse Rosa26 locus to permit cell type-specific expression of this pathogenic allele...
2016: PloS One
https://www.readbyqxmd.com/read/27895764/mitofusin-2-prevents-skeletal-muscle-wasting-in-cancer-cachexia
#17
Qiu-Lei Xi, Bo Zhang, Yi Jiang, Hai-Sheng Zhang, Qing-Yang Meng, Ying Chen, Yu-Song Han, Qiu-Lin Zhuang, Jun Han, Hai-Yu Wang, Jing Fang, Guo-Hao Wu
Cancer cachexia remains a leading cause of morbidity and mortality worldwide, despite extensive research and clinical trials. The prominent clinical feature of cancer cachexia is the continuous loss of skeletal muscle that cannot be fully reversed by conventional nutritional support, and that leads to progressive functional impairment. The mechanism underlying muscle loss in patients with cachexia is poorly understood. The present study analyzed 21 cancer patients with or without cachexia, and demonstrated that mitofusin-2 (Mfn2) was downregulated in the rectus abdominis of patients with cachexia, which was associated with body weight loss...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27862672/clinical-and-genetic-spectra-of-charcot-marie-tooth-disease-in-chinese-han-patients
#18
Bo Sun, Zhaohui Chen, Li Ling, Fei Yang, Xusheng Huang
Charcot-Marie-Tooth disease (CMT) is a common hereditary motor and sensory neuropathy. Epidemiological data for Chinese CMT patients are few. This study aimed to analyze the electrophysiological and genetic characteristics of Chinese Han patients. 106 unrelated patients with the clinical diagnosis of CMT were included. Clinical examination, nerve conduction studies (NCS), next-generation sequencing (NGS), and bioinformatic analyses were performed. Genetic testing was performed for 82 patients; 27 (33%) patients carried known CMT-associated gene mutations...
November 8, 2016: Journal of the Peripheral Nervous System: JPNS
https://www.readbyqxmd.com/read/27847330/altered-mitochondrial-quality-control-signaling-in-muscle-of-old-gastric-cancer-patients-with-cachexia
#19
Emanuele Marzetti, Maria Lorenzi, Francesco Landi, Anna Picca, Fausto Rosa, Fabiana Tanganelli, Marco Galli, Giovanni Battista Doglietto, Fabio Pacelli, Matteo Cesari, Roberto Bernabei, Riccardo Calvani, Maurizio Bossola
Mitochondrial dysfunction is involved in the loss of muscle featuring both aging and cancer cachexia (CC). Whether mitochondrial quality control (MQC) is altered in skeletal myocytes of old patients with CC is unclear. The present investigation therefore sought to preliminarily characterize MQC pathways in muscle of old gastric cancer patients with cachexia. The study followed a case-control cross-sectional design. Intraoperative biopsies of the rectus abdominis muscle were obtained from 18 patients with gastric adenocarcinoma (nine with CC and nine non-cachectic) and nine controls, and assayed for the expression of a set of MQC mediators...
January 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/27847271/oleuropein-improves-mitochondrial-function-to-attenuate-oxidative-stress-by-activating-the-nrf2-pathway-in-the-hypothalamic-paraventricular-nucleus-of-spontaneously-hypertensive-rats
#20
Wenyan Sun, Xin Wang, Chen Hou, Liang Yang, Hongbao Li, Jing Guo, Chanjuan Huo, Molin Wang, Yuwang Miao, Jiankang Liu, Yuming Kang
Hypertension is associated with increased reactive oxygen species (ROS) production in the paraventricular nucleus (PVN) of the hypothalamus. Oleuropein (OL) has a variety of biochemical roles, including antihypertensive and antioxidative functions. However, there have been few reports on the effects of OL on oxidative stress in the PVN on hypertension. In spontaneously hypertensive rats (SHR), eight-week administration of 60 mg/kg/day of OL significantly reduced blood pressure, pro-inflammatory cytokines and the expression of components of the renin-angiotensin system (RAS) compared with SHR rats treated with saline...
February 2017: Neuropharmacology
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