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https://www.readbyqxmd.com/read/28904083/assessing-the-effects-of-mitofusin-2-deficiency-in-the-adult-heart-using-3d-electron-tomography
#1
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
https://www.readbyqxmd.com/read/28902413/frequent-genes-in-rare-diseases-panel-based-next-generation-sequencing-to-disclose-causal-mutations-in-hereditary-neuropathies
#2
Maike F Dohrn, Nicola Glöckle, Lejla Mulahasanovic, Corina Heller, Julia Mohr, Christine Bauer, Erik Riesch, Andrea Becker, Florian Battke, Konstanze Hörtnagel, Thorsten Hornemann, Saranya Suriyanarayanan, Markus Blankenburg, Jörg B Schulz, Kristl G Claeys, Burkhard Gess, Istvan Katona, Andreas Ferbert, Debora Vittore, Alexander Grimm, Stefan Wolking, Ludger Schöls, Holger Lerche, G Christoph Korenke, Dirk Fischer, Bertold Schrank, Urania Kotzaeridou, Gerhard Kurlemann, Bianca Dräger, Anja Schirmacher, Peter Young, Beate Schlotter-Weigel, Saskia Biskup
Hereditary neuropathies comprise a wide variety of chronic diseases associated to more than 80 genes identified to date. We herein examined 612 index patients with either a Charcot-Marie-Tooth phenotype, hereditary sensory neuropathy, familial amyloid neuropathy, or small fiber neuropathy using a customized multigene panel based on the next generation sequencing (NGS) technique. In 121 cases (19.8%), we identified at least one putative pathogenic mutation. Out of these, 54.4% showed an autosomal dominant, 33...
September 13, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28901427/microrna%C3%A2-106b-regulates-skeletal-muscle-insulin-sensitivity-and-glucose-homeostasis-by-targeting-mitofusion%C3%A2-2
#3
Ying Zhang, Wei He, Yuan-Fu Gao, Zhong-Min Fan, Chun-Lin Gao, Zheng-Kun Xia
MicroRNA‑106b (miR‑106b) is reported to be closely associated with skeletal muscle insulin resistance. The present study further investigated the role of miR‑106b in skeletal muscle insulin sensitivity and glucose homeostasis in vivo. Mice were randomly divided into 4 groups and infected with lentivirus expressing miR‑106b (miR‑106b mice), miR‑106b sponge (miR‑106b inhibition mice) or the corresponding empty vectors. Mitofusion‑2 (Mfn2) protein expression levels and glucose transporter (Glut)‑4 protein translocation were significantly reduced in the muscle of miR‑106b mice, whereas they were unaffected in miR‑106b inhibition mice...
September 8, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28860994/pioglitazone-improves-mitochondrial-function-in-the-remnant-kidney-and-protects-against-renal-fibrosis-in-5-6-nephrectomized-rats
#4
Li Sun, Quan Yuan, Tianhua Xu, Li Yao, Jiangmin Feng, Jianfei Ma, Lining Wang, Changlong Lu, Danan Wang
Pioglitazone is a type of peroxisome proliferator-activated receptor γ (PPARγ) agonist and has been demonstrated to be effective in chronic kidney diseases (CKD) treatment. However, the underlying mechanism involved in the renoprotection of pioglitazone has not been fully revealed. In the present study, the renoprotective mechanism of pioglitazone was investigated in 5/6 nephrectomized (Nx) rats and TGF-β1-exposed HK-2 cells. Pioglitazone attenuated renal injury and improved renal function, as examined by 24 h urinary protein, blood urea nitrogen and plasma creatinine in Nx rats...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28859443/imbalance-in-mitochondrial-dynamics-and-apoptosis-in-pregnancies-among-hiv-infected-women-on-haart-with-obstetric-complications
#5
Mariona Guitart-Mampel, A Sandra Hernandez, Constanza Moren, Marc Catalan-Garcia, Ester Tobias, Ingrid Gonzalez-Casacuberta, Diana L Juarez-Flores, Josep M Gatell, Francesc Cardellach, Jose C Milisenda, Josep M Grau, Eduard Gratacos, Francesc Figueras, Gloria Garrabou
Background: HIV infection and HAART trigger genetic and functional mitochondrial alterations leading to cell death and adverse clinical manifestations. Mitochondrial dynamics enable mitochondrial turnover and degradation of damaged mitochondria, which may lead to apoptosis. Objectives: To evaluate markers of mitochondrial dynamics and apoptosis in pregnancies among HIV-infected women on HAART and determine their potential association with obstetric complications...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28845591/mitochondrial-degeneration-precedes-the-development-of-muscle-atrophy-in-progression-of-cancer-cachexia-in-tumour-bearing-mice
#6
Jacob L Brown, Megan E Rosa-Caldwell, David E Lee, Thomas A Blackwell, Lemuel A Brown, Richard A Perry, Wesley S Haynie, Justin P Hardee, James A Carson, Michael P Wiggs, Tyrone A Washington, Nicholas P Greene
BACKGROUND: Cancer cachexia is largely irreversible, at least via nutritional means, and responsible for 20-40% of cancer-related deaths. Therefore, preventive measures are of primary importance; however, little is known about muscle perturbations prior to onset of cachexia. Cancer cachexia is associated with mitochondrial degeneration; yet, it remains to be determined if mitochondrial degeneration precedes muscle wasting in cancer cachexia. Therefore, our purpose was to determine if mitochondrial degeneration precedes cancer-induced muscle wasting in tumour-bearing mice...
August 28, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/28833102/tetrahydrocurcumin-ameliorates-homocysteine-mediated-mitochondrial-remodeling-in-brain-endothelial-cells
#7
Jonathan C Vacek, Jyotirmaya Behera, Akash K George, Pradip K Kamat, Anuradha Kalani, Neetu Tyagi
Homocysteine (Hcy) causes endothelial dysfunction by inducing oxidative stress in most neurodegenerative disorders. This dysfunction is highly correlated with mitochondrial dynamics such as fusion and fission. However, there are no strategies to prevent Hcy induced mitochondrial remodeling. Tetrahydrocurcumin (THC) is an anti-inflammatory and anti-oxidant compound. We hypothesized that THC may ameliorates Hcy induced mitochondria remodeling in mouse brain endothelial cells (bEnd3) cells. bEnd3 cells were exposed to Hcy treatment in the presence or absence of THC...
August 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28807823/dietary-supplementation-with-acetyl-l-carnitine-counteracts-age-related-alterations-of-mitochondrial-biogenesis-dynamics-and-antioxidant-defenses-in-brain-of-old-rats
#8
Luigi Nicassio, Flavio Fracasso, Giuseppe Sirago, Clara Musicco, Anna Picca, Emanuele Marzetti, Riccardo Calvani, Palmiro Cantatore, Maria Nicola Gadaleta, Vito Pesce
We previously reported the ability of dietary supplementation with acetyl-l-carnitine (ALCAR) to prevent age-related decreases of mitochondrial biogenesis in skeletal muscle and liver of old rats. Here, we investigate the effects of ALCAR supplementation in cerebral hemispheres and cerebellum of old rats by analyzing several parameters linked to mitochondrial biogenesis, mitochondrial dynamics and antioxidant defenses. We measured the level of the coactivators PGC-1α and PGC-1β and of the factors regulating mitochondrial biogenesis, finding an age-related decrease of PGC-1β, whereas PGC-1α level was unvaried...
August 12, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28796392/natural-history-of-charcot-marie-tooth-disease-during-childhood
#9
Kayla Md Cornett, Manoj P Menezes, Rosemary R Shy, Isabella Moroni, Emanuela Pagliano, Davide Pareyson, Timothy Estilow, Sabrina W Yum, Trupti Bhandari, Francesco Muntoni, Matilde Laura, Mary M Reilly, Richard S Finkel, Kate J Eichinger, David N Herrmann, Paula Bray, Mark Halaki, Michael E Shy, Joshua Burns
OBJECTIVE: To determine the rate of disease progression in a longitudinal natural history study of children with Charcot-Marie-Tooth disease (CMT). METHODS: 206 (103 female) participants aged 3-20 years enrolled in the Inherited Neuropathies Consortium were assessed at baseline and 2-years. Demographic, anthropometric, and diagnostic information were collected. Disease progression was assessed with the CMT Pediatric Scale (CMTPedS), a reliable Rasch-built linearly weighted disability scale evaluating fine and gross motor function, strength, sensation, and balance...
August 10, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28782654/mir-485-5p-modulates-mitochondrial-fission-through-targeting-mitochondrial-anchored-protein-ligase-in-cardiac-hypertrophy
#10
Yanfang Zhao, Murugavel Ponnusamy, Cuiyun Liu, Jing Tian, Yanhan Dong, Jinning Gao, Chaoqun Wang, Yuan Zhang, Lei Zhang, Kun Wang, Peifeng Li
The pathogenesis of cardiac hypertrophy is tightly associated with mitochondrial dysfunction. Disequilibrium of mitochondrial dynamic is one of the main drivers in the pathological processes during development of various cardiac diseases. However, the effect of mitochondrial dynamics on cardiac hypertrophy remains largely unclear. MicroRNAs (miRNAs) are small noncoding RNAs that can switch off expression of many genes. Mitochondrial anchored protein ligase (MAPL) is a small ubiquitin-like modifier (SUMO) E3 ligase, which is an important contributor in mitochondrial fission process...
August 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28772265/microrna-214-affects-fibroblast-differentiation-of-adipose-derived-mesenchymal-stem-cells-by-targeting-mitofusin-2-during-pelvic-floor-dysfunction-in-sd-rats-with-birth-trauma
#11
Jing Wu, Jiang Li, Wei-Kang Chen, Shang Liu, Jian-He Liu, Jing-Song Zhang, Ke-Wei Fang
BACKGROUND/AIMS: This study investigated whether microRNA-214 (miR-214) targets mitofusin-2 (Mfn2) in the process of fibroblast differentiation of adipose-derived mesenchymal stem cells (ADMSCs) during pelvic floor dysfunction (PFD) in Sprague Dawley (SD) rats with birth trauma. METHODS: The ADMSCs were isolated from 4-6 week male SD rats (n = 20) and were cultured and divided into the blank, miR-214 mimic negative control (NC), miR-214 mimic, miR-214 inhibitor NC, miR-214 inhibitor, empty vector, Mfn2 over-expression and miR-214 + Mfn2 over-expression groups...
August 3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28771897/clinical-and-mutational-spectrum-of-charcot-marie-tooth-disease-type-2z-caused-by-morc2-variants-in-japan
#12
M Ando, Y Okamoto, A Yoshimura, J-H Yuan, Y Hiramatsu, Y Higuchi, A Hashiguchi, J Mitsui, H Ishiura, S Fukumura, M Matsushima, N Ochi, J Tsugawa, S Morishita, S Tsuji, H Takashima
BACKGROUND AND PURPOSE: The microrchidia family CW-type zinc finger 2 gene (MORC2) was newly identified as a causative gene of Charcot-Marie-Tooth disease (CMT) type 2Z in 2016. We aimed to describe the clinical and mutational spectrum of patients with CMT harboring MORC2 mutations in Japan. METHODS: We analyzed samples from 781 unrelated patients clinically diagnosed with CMT using deoxyribonucleic acid microarray or targeted resequencing by next-generation sequencing, and samples from 434 mutation-negative patients were subjected to whole-exome sequencing...
August 3, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28755984/penehyclidine-hydrochloride-preconditioning-provides-cardiac-protection-in-a-rat-model-of-myocardial-ischemia-reperfusion-injury-via-the-mechanism-of-mitochondrial-dynamics-mechanism
#13
Yanli Yang, Liyun Zhao, Jun Ma
To investigate that penehyclidine hydrochloride (PHC) plays a cardiac protection role in myocardial ischemia/reperfusion injury (IRI) through mitochondrial dynamics mechanism. Rat model of myocardial I/R injury was established by the ligation of left anterior descending coronary artery for 30min followed by 3h perfusion. Before I/R, the rats were pretreated with or without PHC. Cardiac function was measured by echocardiography. The activities/levels of myocardial enzymes, oxidants and antioxidant enzymes were detected...
July 26, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28751712/activation-of-mitophagy-leads-to-decline-in-mfn2-and-loss-of-mitochondrial-mass-in-fuchs-endothelial-corneal-dystrophy
#14
Anne-Sophie Benischke, Shivakumar Vasanth, Takashi Miyai, Kishore Reddy Katikireddy, Tomas White, Yuming Chen, Adna Halilovic, Marianne Price, Francis Price, Paloma B Liton, Ula V Jurkunas
Human corneal endothelial cells (HCEnCs) are terminally differentiated cells that have limited regenerative potential. The large numbers of mitochondria in HCEnCs are critical for pump and barrier function required for corneal hydration and transparency. Fuchs Endothelial Corneal Dystrophy (FECD) is a highly prevalent late-onset oxidative stress disorder characterized by progressive loss of HCEnCs. We previously reported increased mitochondrial fragmentation and reduced ATP and mtDNA copy number in FECD. Herein, carbonyl cyanide m-chlorophenyl hydrazone (CCCP)-induced mitochondrial depolarization decreased mitochondrial mass and Mfn2 levels, which were rescued with mitophagy blocker, bafilomycin, in FECD...
July 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28746876/wbscr16-is-a-guanine-nucleotide-exchange-factor-important-for-mitochondrial-fusion
#15
Guorui Huang, Dawiyat Massoudi, Alison M Muir, Dinesh C Joshi, Chuan-Li Zhang, Shing Yan Chiu, Daniel S Greenspan
Regulated inter-mitochondrial fusion/fission is essential for maintaining optimal mitochondrial respiration and control of apoptosis and autophagy. In mammals, mitochondrial fusion is controlled by outer membrane GTPases MFN1 and MFN2 and by inner membrane (IM) GTPase OPA1. Disordered mitochondrial fusion/fission contributes to various pathologies, and MFN2 or OPA1 mutations underlie neurodegenerative diseases. Here, we show that the WBSCR16 protein is primarily associated with the outer face of the inner mitochondrial membrane and is important for mitochondrial fusion...
July 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28743390/baicalin-attenuates-in-vivo-and-in-vitro-hyperglycemia-exacerbated-ischemia-reperfusion-injury-by-regulating-mitochondrial-function-in-a-manner-dependent-on-ampk
#16
Shanshan Li, Xiaoxu Sun, Lixing Xu, Ruoxi Sun, Zhanqiang Ma, Xueyang Deng, Baolin Liu, Qiang Fu, Rong Qu, Shiping Ma
Cerebral ischemia/reperfusion (I/R) is a lethal and disabling disease. Studies have suggested that hyperglycemia is a risk factor for cerebral I/R. Baicalin is a natural bioactive flavonoid extracted from Scutellaria baicalensis Georgi with neuroprotective activity. In the present study, we investigated the effects of baicalin on hyperglycemia-exacerbated cerebral I/R injury. Streptozotocin (STZ) injection aggravated the brain damage induced by middle cerebral artery occlusion (MCAO) surgery, while baicalin administration reduced blood glucose, relieved neurological deficit and decreased infarct volume...
July 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28729638/inhibition-of-microrna-214-promotes-epithelial-mesenchymal-transition-process-and-induces-interstitial-cystitis-in-postmenopausal-women-by-upregulating-mfn2
#17
Jian-Wei Lv, Wei Wen, Chen Jiang, Qi-Bo Fu, Yin-Jun Gu, Ting-Ting Lv, Zhen-Dong Li, Wei Xue
Our study aims to investigate the roles that microRNA-214 (miR-214) plays in the epithelial mesenchymal transition (EMT) process and the development of interstitial cystitis (IC) in postmenopausal women by targeting Mitofusin 2 (Mfn2). IC bladder tissues and adjacent normal bladder tissues were collected from postmenopausal women. Immunohistochemistry (IHC) staining was conducted. The target relationship between miR-214 and Mfn2 was determined by a dual luciferase reporter gene assay. Adipose-derived mesenchymal stem cells (ADMSCs) were extracted from postmenopausal rats and assigned to the blank, mimics, miR-214 inhibitors, mimics negative control (NC), inhibitors NC, Mfn2 siRNA, miR-214 inhibitors and Mfn2 siRNA groups...
July 21, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28713932/human-trypsin-inhibitor-reduces-the-apoptosis-of-lipopolysaccharide%C3%A2-induced-human-kidney%C3%A2-2-cells-by-promoting-mitochondrial-fusion
#18
Ning Liu, Zhiyi Jiang, Yongjun Liu, Yao Nie, Juan Chen, Bin Ouyang, Xiangdong Guan, Minying Chen
Imbalance in mitochondrial fusion/fission is one of the mechanisms leading to sepsis‑induced mitochondrial dysfunction and cell apoptosis. The present study examined the effects of human trypsin inhibitor (UTI), a well‑known antioxidant and anti‑inflammatory substance, on mitochondrial dynamics and cell apoptosis in lipopolysaccharide (LPS)‑induced human kidney‑2 (HK‑2) cells. The HK‑2 cells were incubated for 24 h either with LPS (800 ng/ml) or LPS (800 ng/ml) mixed with UTI (250 U/ml). Cell viability was assessed using a3‑(4,5‑dimethyl‑2‑thiazolyl)‑2, 5‑diphenyl‑2‑H‑tetrazolium bromide assay...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28712398/-fasudil-attenuates-mitochondrial-injury-and-apoptosis-in-rat-model-of-myocardial-ischemia-reperfusion-injury
#19
Hongwei Ye, Guanjun Zhang, Ruiping Cao, Pinfang Kang, Zhenghong Li, Qin Gao
Objective To observe the changes of mitochondria fusion protein 2 (Mfn2) and dynamin-related protein 1 (Drp1) in the cardioprotection of fasudil, and analyze the significance. Methods Hearts isolated from male Sprague-Dawley rats were subjected to ischemia for 30 minutes (occlusion of left anterior descending artery), and continuously perfusion for 120 minutes to establish myocardial ischemia/reperfusion (I/R) injury model. The rats were divided into 3 groups: sham group, I/R group and fasudil group. The left ventricular hemodynamics were continuously recorded; lactate dehydrogenase (LDH) content was measured during reperfusion; myocardial ultrastructure was observed by electron microscopy; the protein expression of phosphorylated protein phosphatase 1 regulatory subunit 12A (p-PPP1R12A/p-MYPT1) was detected by immunohistochemistry; and the protein expressions of Mfn2, Drp1 and cleaved caspase-3 (c-caspase-3) were detected by Western blot analysis...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28705993/effects-of-%C3%AE-hydroxy-%C3%AE-methylbutyrate-hmb-on-skeletal-muscle-mitochondrial-content-and-dynamics-and-lipids-after-10-days-of-bed-rest-in-older-adults
#20
Robert A Standley, Giovanna Distefano, Suzette L Pereira, Min Tian, Owen J Kelly, Paul M Coen, Nicolaas E P Deutz, Robert R Wolfe, Bret H Goodpaster
Loss of muscle mass during periods of disuse likely has negative health consequences for older adults. We have previously shown that β-hydroxy-β-methylbutyrate (HMB) supplementation during 10 days of strict bed rest (BR) attenuates the loss of lean mass in older adults. To elucidate potential molecular mechanisms of HMB effects on muscle during bed rest and resistance training rehabilitation (RT), we examined mediators of skeletal muscle mitochondrial dynamics, autophagy and atrophy, and intramyocellular lipids...
July 13, 2017: Journal of Applied Physiology
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