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https://www.readbyqxmd.com/read/29351829/inhibition-of-dynamin-related-protein-1-has-neuroprotective-effect-comparable-with-therapeutic-hypothermia-in-a-rat-model-of-cardiac-arrest
#1
Peng Wang, Yi Li, Zhengfei Yang, Tao Yu, Guanghui Zheng, Xiangshao Fang, Zitong Huang, Longyuan Jiang, Wanchun Tang
Dynamin-related protein 1 (Drp1) regulates mitochondrial fission, it has been proven that inhibition of Drp1 by mdivi-1 improves survival and attenuates cerebral ischemic injury after cardiac arrest. In this study, we compared the effects of Drp1 inhibition with therapeutic hypothermia on post-resuscitation neurologic injury in a rat model of cardiac arrest. Rats were randomized into 4 groups: Mdivi-1 treatment group (n = 39), hypothermic group (n = 38), normothermic group (n = 41), and sham group (n = 12)...
January 8, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29348461/loss-of-cdk5-in-breast-cancer-cells-promotes-ros-mediated-cell-death-through-dysregulation-of-the-mitochondrial-permeability-transition-pore
#2
Saranya NavaneethaKrishnan, Jesusa L Rosales, Ki-Young Lee
Cdk5, which plays a role in the development and progression of many human cancers, localizes in the mitochondria, a key determinant of apoptotic cell death. Cdk5 is upregulated in breast cancer cells but it was shown that Cdk5 loss increases chemotherapy-induced apoptosis. However, the molecular mechanism by which Cdk5 loss promotes cell death remains unclear. Here, we investigate the possibility that Cdk5 loss activates the intrinsic apoptotic pathway in breast cancer cells. We demonstrate that Cdk5-deficient breast cancer cells exhibit increased mitochondrial depolarization, mitochondrial ROS levels, and mitochondrial fragmentation that is associated with an increase in both intracellular Ca2+ level and calcineurin activity, and DRP1 S637 dephosphorylation...
January 19, 2018: Oncogene
https://www.readbyqxmd.com/read/29345339/the-role-of-cdk5-mediated-drp1-phosphorylation-in-a%C3%AE-1-42-induced-mitochondrial-fission-and-neuronal-apoptosis
#3
Miao-Yu Guo, Lei Shang, Yang-Yang Hu, Li-Ping Jiang, Yu-Ying Wan, Qin-Qin Zhou, Kun Zhang, Hong-Fei Liao, Jing-Lin Yi, Xiao-Jian Han
Alzheimer's disease, one of the most common neurodegenerative diseases, is pathologically characterized by Amyloid beta containing plaques and neurofibrillary tangles. Amyloid beta (Aβ) induces neuronal apoptosis through the intracellular Ca2+ increase, subsequent hyperactivation of cyclin-dependent kinase 5 (Cdk5) and mitochondrial abnormality. Recently, Cdk5 was identified as an upstream regulator of mitochondrial fission during neuronal apoptosis, but the underlying mechanism remains unclear. Here, in vitro phosphorylation assays showed that Cdk5 could phosphorylate the recombinant Drp1 at Serine 579...
January 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29344294/cardiomyocyte-restricted-low-density-lipoprotein-receptor-related-protein-6-lrp6-deletion-leads-to-lethal-dilated-cardiomyopathy-partly-through-drp1-signaling
#4
Zhidan Chen, Yang Li, Ying Wang, Juying Qian, Hong Ma, Xiang Wang, Guoliang Jiang, Ming Liu, Yanpeng An, Leilei Ma, Le Kang, Jianguo Jia, Chunjie Yang, Guoping Zhang, Ying Chen, Wei Gao, Mingqiang Fu, Zheyong Huang, Huiru Tang, Yichun Zhu, Junbo Ge, Hui Gong, Yunzeng Zou
Low density lipoprotein receptor-related protein 6 (LRP6), a wnt co-receptor, regulates multiple functions in various organs. However, the roles of LRP6 in the adult heart are not well understood. Methods: We observed LRP6 expression in heart with end-stage dilated cardiomyopathy (DCM) by western blot. Tamoxifen-inducible cardiac-specific LRP6 knockout mouse was constructed. Hemodynamic and echocardiographic analyses were performed to these mice. Results: Cardiac LRP6 expression was dramatically decreased in patients with end-stage dilated cardiomyopathy (DCM) compared to control group...
2018: Theranostics
https://www.readbyqxmd.com/read/29339725/tgr5-signalling-promotes-mitochondrial-fission-and-beige-remodelling-of-white-adipose-tissue
#5
Laura A Velazquez-Villegas, Alessia Perino, Vera Lemos, Marika Zietak, Mitsunori Nomura, Thijs Willem Hendrik Pols, Kristina Schoonjans
Remodelling of energy storing white fat into energy expending beige fat could be a promising strategy to reduce adiposity. Here, we show that the bile acid-responsive membrane receptor TGR5 mediates beiging of the subcutaneous white adipose tissue (scWAT) under multiple environmental cues including cold exposure and prolonged high-fat diet feeding. Moreover, administration of TGR5-selective bile acid mimetics to thermoneutral housed mice leads to the appearance of beige adipocyte markers and increases mitochondrial content in the scWAT of Tgr5 +/+ mice but not in their Tgr5 -/- littermates...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29339557/chronic-dietary-creatine-enhances-hippocampal-dependent-spatial-memory-bioenergetics-and-levels-of-plasticity-related-proteins-associated-with-nf-%C3%AE%C2%BAb
#6
Wanda M Snow, Chris Cadonic, Claudia Cortes-Perez, Subir K Roy Chowdhury, Jelena Djordjevic, Ella Thomson, Michael J Bernstein, Miyoung Suh, Paul Fernyhough, Benedict C Albensi
The brain has a high demand for energy, of which creatine (Cr) is an important regulator. Studies document neurocognitive benefits of oral Cr in mammals, yet little is known regarding their physiological basis. This study investigated the effects of Cr supplementation (3%, w/w) on hippocampal function in male C57BL/6 mice, including spatial learning and memory in the Morris water maze and oxygen consumption rates from isolated mitochondria in real time. Levels of transcription factors and related proteins (CREB, Egr1, and IκB to indicate NF-κB activity), proteins implicated in cognition (CaMKII, PSD-95, and Egr2), and mitochondrial proteins (electron transport chain Complex I, mitochondrial fission protein Drp1) were probed with Western blotting...
February 2018: Learning & Memory
https://www.readbyqxmd.com/read/29336470/tnf-%C3%AE-induces-drp1-mediated-mitochondrial-fragmentation-during-inflammatory-cardiomyocyte-injury
#7
Yue-Liang Shen, Ying-Zhou Shi, Gai-Ge Chen, Lin-Lin Wang, Ming-Zhi Zheng, Hong-Feng Jin, Ying-Ying Chen
Dynamin-related peptide 1 (Drpl)-mediated mitochondrial fission is an important process associated with cardiac dysfunction under different pathological conditions. The aim of the present study was to investigate the expression of Drpl during inflammatory myocardial injury. Sprague‑Dawley rats were treated intraperitoneally with lipopolysaccharides (LPS). Furthermore, cultured H9C2 cardiomyocytes were treated with LPS, interleukin‑6 (IL‑6) and tumor necrosis factor‑α (TNF‑α). Total and mitochondrial proteins were isolated from the heart tissue of rats and from the H9C2 cardiomyocytes...
January 15, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29335339/inhibition-of-drp1-fis1-interaction-slows-progression-of-amyotrophic-lateral-sclerosis
#8
Amit U Joshi, Nay L Saw, Hannes Vogel, Anna D Cunnigham, Mehrdad Shamloo, Daria Mochly-Rosen
Bioenergetic failure and oxidative stress are common pathological hallmarks of amyotrophic lateral sclerosis (ALS), but whether these could be targeted effectively for novel therapeutic intervention needs to be determined. One of the reported contributors to ALS pathology is mitochondrial dysfunction associated with excessive mitochondrial fission and fragmentation, which is predominantly mediated by Drp1 hyperactivation. Here, we determined whether inhibition of excessive fission by inhibiting Drp1/Fis1 interaction affects disease progression...
January 15, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29329364/downregulation-of-drp1-a-fission-regulator-is-associated-with-human-lung-and-colon-cancers
#9
Young Yeon Kim, Seong-Hoon Yun, Jeanho Yun
Dynamin-related protein 1 (Drp1), a dynamin-related GTPase, is a key regulator of mitochondrial fission. Although recent studies have shown that Drp1 plays important roles in various important cellular processes, such as maintaining proper mitochondrial function, apoptosis and necrosis, the potential involvement of Drp1 in cancer development has not been fully addressed. To explore the role of Drp1 in cancer, we examined Drp1 levels in various human cancer tissues. Tissue array analysis showed that the level of Drp1 was decreased significantly in malignant colon and lung cancer tissues, whereas no change in Drp1 was observed in breast and prostate tumors...
January 10, 2018: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29322081/data-of-expression-status-of-mir-29a-and-its-putative-target-mitochondrial-apoptosis-regulatory-gene-drp1-upon-mir-15a-and-mir-214-inhibition
#10
Muhammad Ishtiaq Jan, Riaz Anwar Khan, Abdul Malik, Tahir Ali, Muhammad Bilal, Long Bo, Abdul Sajid, Naseeb Urehman, Nayyar Waseem, Javed Nawab, Murad Ali, Abdul Majeed, Hamid Ahmad, Sohail Aslam, Sadia Hamera, Aneesa Sultan, Mariam Aneesa, Qamar Javed, Iram Murtaza
Data is about the mitochondrial apoptosis regulatory framework genes PUMA, DRP1 (apoptotic), and ARC (anti-apoptotic) analysis after the employment of their controlling miRNAs inhibitors. The data represents putative conserved targeting of seed regions of miR-15a, miR-29a, and miR-214 with respective target genes PUMA, DRP1, and ARC. Data is of cross interference in expression levels of one miRNA family, miR-29a and its putative target DRP1 upon the inhibitory treatment of other miRNAs 15a and 214.
February 2018: Data in Brief
https://www.readbyqxmd.com/read/29317239/protective-effect-of-mitochondrial-targeted-antioxidant-mitoq-against-iron-ion-56fe-radiation-induced-brain-injury-in-mice
#11
Lu Gan, Zhenhua Wang, Jing Si, Rong Zhou, Chao Sun, Yang Liu, Yancheng Ye, Yanshan Zhang, Zhiyuan Liu, Hong Zhang
Exposure to iron ion 56Fe radiation (IR) during space missions poses a significant risk to the central nervous system and radiation exposure is intimately linked to the production of reactive oxygen species (ROS). MitoQ is a mitochondria-targeted antioxidant that has been shown to decrease oxidative damage and lower mitochondrial ROS in a number of animal models. Therefore, the present study aimed to investigate role of the mitochondrial targeted antioxidant MitoQ against 56Fe particle irradiation-induced oxidative damage and mitochondria dysfunction in the mouse brains...
January 6, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29314417/a-nestin-cdk5-drp1-axis-regulates-neural-stem-progenitor-cell-stemness-via-a-metabolic-shift
#12
Jiancheng Wang, Yinong Huang, Jianye Cai, Qiong Ke, Jiaqi Xiao, Weijun Huang, Hongyu Li, Yuan Qiu, Yi Wang, Bin Zhang, Haoxiang Wu, Yanan Zhang, Xin Sui, Adham Sameer A Bardeesi, Andy Peng Xiang
Neural stem/progenitor cells (NSPCs) transplantation provides an alternative approach for various central nervous system (CNS) diseases treatment, while the difficulties in NSPC acquisition and expansion limit their further application. Unveiling the mechanism of NSPC stemness regulation may contribute to its further application. Nestin, generally recognized as a marker of NSPCs, plays a crucial role in the CNS development and NSPC stemness maintenance. Here, we report that Nestin loss triggers mitochondrial network remodeling and enhances oxidative phosphorylation (OXPHOS) in NSPCs treated with Nestin RNA interference (RNAi)...
January 3, 2018: Stem Cells
https://www.readbyqxmd.com/read/29307080/inhibition-of-peroxynitrite-induced-mitophagy-activation-attenuates-cerebral-ischemia-reperfusion-injury
#13
Jinghan Feng, Xingmiao Chen, Binghe Guan, Caiming Li, Jinhua Qiu, Jiangang Shen
Activated autophagy/mitophagy has been intensively observed in ischemic brain, but its roles remain controversial. Peroxynitrite (ONOO-), as a representative of reactive nitrogen species, is considered as a critical neurotoxic factor in mediating cerebral ischemia-reperfusion (I/R) injury, but its roles in autophagy/mitophagy activation remain unclear. Herein, we hypothesized that ONOO- could induce PINK1/Parkin-mediated mitophagy activation via triggering dynamin-related protein 1 (Drp1) recruitment to damaged mitochondria, contributing to cerebral I/R injury...
January 6, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29301103/%C3%AE-synuclein-and-tau-mitochondrial-kill-switches
#14
Ulrike Pech, Patrik Verstreken
α-Synuclein resides in Lewy bodies in Parkinson's disease. Ordonez et al. (2017) now show that α-syn disrupts the actin network, causing Drp1-dependent mitochondrial fission defects. This is similar to defects induced by the PD risk factor Tau, suggesting converging pathways in neurodegeneration.
January 3, 2018: Neuron
https://www.readbyqxmd.com/read/29299119/identifying-mitotane-induced-mitochondria-associated-membranes-dysfunctions-metabolomic-and-lipidomic-approaches
#15
Ségolène Hescot, Larbi Amazit, Marie Lhomme, Simon Travers, Anais DuBow, Stephanie Battini, Geoffrey Boulate, Izzie Jacques Namer, Anne Lombes, Anatol Kontush, Alessio Imperiale, Eric Baudin, Marc Lombes
Mitotane (o,p'DDD), the most effective drug in adrenocortical carcinoma, concentrates into the mitochondria and impacts mitochondrial functions. To address the molecular mechanisms of mitotane action and to identify its potential target, metabolomic and lipidomic approaches as well as imaging analyses were employed in human adrenocortical H295R cells allowing identification of Mitochondria-Associated Membranes dysfunction as a critical impact of mitotane. Study of intracellular energetic metabolites by NMR spectroscopy showed that mitotane significantly decreased aspartate while concomitantly increased glutamate content in a time- and concentration-dependent manner...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29290987/icg-001-affects-drp1-activity-and-er-stress-correlative-with-its-anti-proliferative-effect
#16
Heidi Zinecker, Djamila Ouaret, Daniel Ebner, Moritz M Gaidt, Steve Taylor, Anna Aulicino, Marta Jagielowicz, Veit Hornung, Alison Simmons
Mitochondria form a highly dynamic network driven by opposing scission and fusion events. DRP1 is an essential modulator of mitochondrial fission and dynamics within mammalian cells. Its fission activity is regulated by posttranslational modifications such as activating phosphorylation at serine 616. DRP1 activity has recently been implicated as being dysregulated in numerous human disorders such as cancer and neurodegenerative diseases. Here we describe the development of a cell-based screening assay to detect DRP1 activation...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29261068/expression-of-a-t39n-mutant-rab32-protein-arrests-mitochondria-movement-within-neurites-of-differentiated-sh-sy5y-cells
#17
Jonas Rybnicek, Samira Samtleben, Maria Sol Herrera-Cruz, Thomas Simmen
We have shown that multiple sclerosis (MS) and endoplasmic reticulum (ER) stress induce Rab32, an ER/mitochondria-localized small GTPase. High levels of both dominant-active (Q85L) or dominant-inactive (T39N) Rab32 are toxic to neurons. While Rab32Q85L interacts with its effector Drp1 to promote mitochondria fission, it is unclear how Rab32T39N could result as toxic to neurons. Given the perinuclear clustering of mitochondria observed upon transfection of inactive Rab32, we hypothesized Rab32T39N could stall mitochondria within neurites...
December 20, 2017: Small GTPases
https://www.readbyqxmd.com/read/29249285/%C3%AE-synuclein-induces-mitochondrial-dysfunction-through-spectrin-and-the-actin-cytoskeleton
#18
Dalila G Ordonez, Michael K Lee, Mel B Feany
Genetics and neuropathology strongly link α-synuclein aggregation and neurotoxicity to the pathogenesis of Parkinson's disease and related α-synucleinopathies. Here we describe a new Drosophila model of α-synucleinopathy based on widespread expression of wild-type human α-synuclein, which shows robust neurodegeneration, early-onset locomotor deficits, and abundant α-synuclein aggregation. We use results of forward genetic screening and genetic analysis in our new model to demonstrate that α-synuclein expression promotes reorganization of the actin filament network and consequent mitochondrial dysfunction through altered Drp1 localization...
December 13, 2017: Neuron
https://www.readbyqxmd.com/read/29248491/atorvastatin-exerts-inhibitory-effect-on-endothelial-senescence-in-hyperlipidemic-rats-through-a-mechanism-involving-down-regulation-of-mir-21-5p-203a-3p
#19
Jie-Jie Zhang, Yin-Zhuang Zhang, Jing-Jie Peng, Nian-Sheng Li, Xiao-Ming Xiong, Qi-Lin Ma, Xiu-Ju Luo, Bin Liu, Jun Peng
Statins are reported to exert benefits on endothelial function through a mechanism involving in prevention of endothelial senescence. This study aims to explore whether atorvastatin exerts inhibitory effect on endothelial senescence in hyperlipidemic rats or ox-LDL-treated HUVECs through a mechanism involving suppress of miR-21-5p/203a-3p expression and their downstream pathway. The rats were fed with high-fat diet to establish a hyperlipidemic model, which showed an increase in plasma lipids and endothelial senescence, accompanied by the elevation in plasma levels of miR-21-5p/203a-3p, down-regulation of Drp1 and up-regulation of p53 in the aorta of hyperlipidemic rats; these phenomena were reversed by atorvastatin...
December 14, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/29245958/apelin-protects-against-myocardial-ischemic-injury-by-inhibiting-dynamin-related-protein-1
#20
Wei Xu, Hongwei Yu, Ruixue Ma, Lina Ma, Qiushuang Liu, Huitong Shan, Chengyu Wu, Rong Zhang, Yuhong Zhou, Hongli Shan
It is known that dynamin-related protein 1 (Drp1)-mediated mitochondrial fission plays an important role in ischemic injury of myocardial infarction (MI). Apelin, an endogenous ligand for Apelin receptor, acts as a key modulator of cardiovascular diseases. Here, we examined the effects of Apelin on MI injury and underlying mechanisms. Adult male C57BL/6J mice were treated with Apelin for 4 weeks and then subjected coronary artery ligation (LAD) to induce MI and the protective effects of Apelin on MI injury were evaluated at 6 h post LAD...
November 21, 2017: Oncotarget
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