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https://www.readbyqxmd.com/read/28713989/effects-of-proton-beam-irradiation-on-mitochondrial-biogenesis-in-a-human-colorectal-adenocarcinoma-cell-line
#1
Byung Geun Ha, Sung Suk Jung, Yun Hee Shon
Proton beam therapy has recently been used to improve local control of tumor growth and reduce side-effects by decreasing the global dose to normal tissue. However, the regulatory mechanisms underlying the physiological role of proton beam radiation are not well understood, and many studies are still being conducted regarding these mechanisms. To determine the effects of proton beams on mitochondrial biogenesis, we investigated: mitochondrial DNA (mtDNA) mass; the gene expression of mitochondrial transcription factors, functional regulators, and dynamic-related regulators; and the phosphorylation of the signaling molecules that participate in mitochondrial biogenesis...
July 5, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28712398/-fasudil-attenuates-mitochondrial-injury-and-apoptosis-in-rat-model-of-myocardial-ischemia-reperfusion-injury
#2
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
#3
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
https://www.readbyqxmd.com/read/28703078/chrysophanol-suppresses-pro-inflammatory-response-in-microglia-via-regulation-of-drp1-dependent-mitochondrial-fission
#4
Unbin Chae, Ju-Sik Min, Hanna Lee, Kyung-Sik Song, Hyun-Shik Lee, Hong Jun Lee, Sang-Rae Lee, Dong-Seok Lee
OBJECTIVES: Chrysophanol, also called chrysophanic acid, is a natural anthraquinone compound found in Rheum palmatum. R. palmatum has been used in oriental medicine in ancient East Asia. Microglial cells represent not only the forefront immune defense in the central nervous system but also the most reactive sensors to various threats. However, activated microglia can exert neurotoxic effects via excessive production of cytotoxic molecules and proinflammatory cytokines. Therefore, modulation of microglial cell activation is important for maintaining neuronal function...
July 13, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28698403/identifying-mitotane-induced-mitochondria-associated-membranes-dysfunctions-metabolomic-and-lipidomic-approaches
#5
Ségolène Hescot, Larbi Amazit, Marie Lhomme, Simon Travers, Anais DuBow, Stéphanie Battini, Geoffrey Boulate, Izzie Jacques Namer, Anne Lombès, Anatol Kontush, Alessio Imperiale, Eric Baudin, Marc Lombès
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...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28698145/increase-in-proteins-involved-in-mitochondrial-fission-mitophagy-proteolysis-and-antioxidant-response-in-type-i-endometrial-cancer-as-an-adaptive-response-to-respiratory-complex-i-deficiency
#6
Antonella Cormio, Clara Musicco, Giuseppe Gasparre, Gennaro Cormio, Vito Pesce, Anna Maria Sardanelli, Maria Nicola Gadaleta
Pathogenic mtDNA mutations associated with alterations of respiratory complex I, mitochondrial proliferation (oncocytic-like phenotype) and increase in antioxidant response were previously reported in type I endometrial carcinoma (EC). To evaluate whether in the presence of pathogenic mtDNA mutations other mitochondrial adaptive processes are triggered by cancer cells, the expression level of proteins involved in mitochondrial dynamics, mitophagy, proteolysis and apoptosis were evaluated in type I ECs harboring pathogenic mtDNA mutations and complex I deficiency...
July 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28694451/polymorphic-regulation-of-mitochondrial-fission-and-fusion-modifies-phenotypes-of-microglia-in-neuroinflammation
#7
Mitsuhiko Katoh, Bao Wu, Huy Bang Nguyen, Truc Quynh Thai, Ryo Yamasaki, Haiyan Lu, Anna M Rietsch, Musab M Zorlu, Youichi Shinozaki, Yurika Saitoh, Sei Saitoh, Takashi Sakoh, Kazuhiro Ikenaka, Schuichi Koizumi, Richard M Ransohoff, Nobuhiko Ohno
Microglia are the resident macrophages of the central nervous system and play complex roles in the milieu of diseases including the primary diseases of myelin. Although mitochondria are critical for cellular functions and survival in the nervous system, alterations in and the roles of mitochondrial dynamics and associated signaling in microglia are still poorly understood. In the present study, by combining immunohistochemistry and 3D ultrastructural analyses, we show that mitochondrial fission/fusion in reactive microglia is differentially regulated from that in monocyte-derived macrophages and the ramified microglia of normal white matter in myelin disease models...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28689004/the-role-of-succinate-and-ros-in-reperfusion-injury-a-critical-appraisal
#8
REVIEW
Tatyana N Andrienko, Philippe Pasdois, Gonçalo C Pereira, Matthew J Ovens, Andrew P Halestrap
We critically assess the proposal that succinate-fuelled reverse electron flow (REF) drives mitochondrial matrix superoxide production from Complex I early in reperfusion, thus acting as a key mediator of ischemia/reperfusion (IR) injury. Real-time surface fluorescence measurements of NAD(P)H and flavoprotein redox state suggest that conditions are unfavourable for REF during early reperfusion. Furthermore, rapid loss of succinate accumulated during ischemia can be explained by its efflux rather than oxidation...
July 5, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28683400/azidothymidine-triphosphate-impairs-mitochondrial-dynamics-by-disrupting-the-quality-control-system
#9
Ryosuke Nomura, Takeya Sato, Yuka Sato, Jeffrey A Medin, Shigeki Kushimoto, Teruyuki Yanagisawa
Highly active anti-retrovirus therapy (HAART) has been used to block the progression and symptoms of human immunodeficiency virus infection. Although it decreases morbidity and mortality, clinical use of HAART has also been linked to various adverse effects such as severe cardiomyopathy resulting from compromised mitochondrial functioning. However, the mechanistic basis for these effects remains unclear. Here, we demonstrate that a key component of HAART, 3ꞌ-azido-3ꞌ-deoxythymidine (AZT), particularly, its active metabolite AZT-triphosphate (AZT-TP), caused mitochondrial dysfunction, leading to induction of cell death in H9c2 cells derived from rat embryonic myoblasts, which serve as a model for cardiomyopathy...
June 29, 2017: Redox Biology
https://www.readbyqxmd.com/read/28677814/involvement-of-mitochondrial-dynamics-in-the-antineoplastic-activity-of-cisplatin-in-murine-leukemia-l1210-cells
#10
Xiao-Jian Han, Sheng-Lan Shi, Yong-Fang Wei, Li-Ping Jiang, Miao-Yu Guo, Hong-Li Wu, Yu-Ying Wan
Leukemia is a type of hematopoietic stem cell malignant cloned disease with high mortality. Cisplatin-based chemotherapy is one of the most common treatments for leukemia. Similar to other chemotherapeutic agents, cisplatin resistance has become a serious issue in cancer therapy. In the present study, we investigated the role of mitochondrial dynamics in the antineoplastic activity of cisplatin in murine leukemia L1210 cells. Firstly, the L1210 cell line resistant to cisplatin (L1210/DDP) was established. Compared to its parental cell line, the IC50 value of cisplatin in the L1210/DDP cells was increased 10-fold...
August 2017: Oncology Reports
https://www.readbyqxmd.com/read/28672961/salidroside-inhibits-high-glucose-induced-proliferation-of-vascular-smooth-muscle-cells-via-inhibiting-mitochondrial-fission-and-oxidative-stress
#11
Xinyu Zhuang, Alimujiang Maimaitijiang, Yong Li, Haiming Shi, Xiaofei Jiang
The mitochondria are highly dynamic organelles, carefully maintaining network homeostasis by regulating mitochondrial fusion and fission. Mitochondrial dynamics are involved in the regulation of a variety of pathophysiological processes, including cell proliferation. Oxidative stress serves an important role in the remodeling of arterial vascular tissue in diabetic patients by affecting the proliferation of vascular smooth muscle cells (VSMCs). Salidroside is the primary active component of Rhodiola rosea and has been demonstrated to be an antioxidant with cardio- and vascular-protective effects, in addition to improving glucose metabolism...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28670625/mechanisms-of-acetaminophen-hepatotoxicity-and-their-translation-to-the-human-pathophysiology
#12
Anup Ramachandran, Hartmut Jaeschke
Acetaminophen (APAP) overdose is the most common cause of acute liver failure in the United States and mechanisms of liver injury induced by APAP overdose have been the focus of extensive investigation. Studies in the mouse model, which closely reproduces the human condition, have shown that hepatotoxicity is initiated by formation of a reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI), which depletes cellular glutathione and forms protein adducts on mitochondrial proteins. This leads to mitochondrial oxidative and nitrosative stress, accompanied by activation of c-jun N-terminal kinase (JNK) and its translocation to the mitochondria...
February 2017: Journal of Clinical and Translational Research
https://www.readbyqxmd.com/read/28659272/p53-drp1-dependent-mitochondrial-fission-mediates-aldosterone-induced-podocyte-injury-and-mitochondrial-dysfunction
#13
Yanggang Yuan, Aiqing Zhang, Jia Qi, Hui Wang, Xi Liu, Min Zhao, Suyan Duan, Zhimin Huang, Chengning Zhang, Lin Wu, Bo Zhang, Aihua Zhang, Changying Xing
Mitochondrial dysfunction is increasingly recognized as an important factor in glomerular diseases. Previous study showed that mitochondrial fission contributed mitochondrial dysfunction. However, the mechanism of mitochondrial fission on mitochondrial dysfunction in aldosterone-induced podocyte injury remains ambiguous. This study aimed to investigate the pathogenic effect of mitochondrial fission both in vivo and in vitro. In an animal model of aldosterone-induced nephropathy, inhibition of the mitochondrial fission protein Drp1 (dynamin-related protein 1) suppressed aldosterone-induced podocyte injury...
June 28, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28646508/hepatic-stimulator-substance-resists-hepatic-ischemia-reperfusion-injury-by-regulating-drp1-translocation-and-activation
#14
Chao Zhang, Jing Huang, Wei An
Ischemia-reperfusion injury (IRI), induced by abnormal mitochondrial fission related apoptosis, is a major concern in liver transplantation settings. Our previous studies have demonstrated that hepatic stimulator substance (HSS) is an anti-apoptotic effector and could protect liver from IRI. However, the underlying mechanism remains unclear. In the present study, we report that in vitro and in vivo HSS could regulate mitochondrial fission and hepatocyte apoptosis during liver IRI by orchestrating the translocation and activation of dynamin-related protein 1 (Drp1)...
June 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28644713/an-unstructured-loop-that-is-critical-for-interactions-of-the-stalk-domain-of-drp1-with-saturated-phosphatidic-acid
#15
Yoshihiro Adachi, Miho Iijima, Hiromi Sesaki
Dynamin-related protein 1 (Drp1) is a dynamin superfamily GTPase, which drives membrane constriction during mitochondrial division. To mediate mitochondrial division, Drp1 is recruited to the mitochondrial outer membrane and is assembled into the division machinery. We previously showed that Drp1 interacts with phosphatidic acid (PA) and saturated phospholipids in the mitochondrial membrane, and this interaction restrains Drp1 in initiating the constriction of mitochondria. Here, we show that the role of saturated acyl chains of phospholipids is independent of their contribution to the membrane curvature or lipid packing suggesting their direct interaction with Drp1...
June 23, 2017: Small GTPases
https://www.readbyqxmd.com/read/28641287/chrysophanol-suppressed-glutamate-induced-hippocampal-neuronal-cell-death-via-regulation-of-dynamin-related-protein-1-dependent-mitochondrial-fission
#16
Unbin Chae, Ju-Sik Min, Hyun Hee Leem, Hyun-Shik Lee, Hong Jun Lee, Sang-Rae Lee, Dong-Seok Lee
Chrysophanic acid, or chrysophanol, is an anthraquinone found in Rheum palmatum, which was used in the preparation of oriental medicine in ancient China. The hippocampus plays a major role in controlling the activities of the short- and long-term memory. It is one of the major regions affected by excessive cell death in Alzheimer's disease. Therefore, neuronal cell-death modulation in the hippocampus is important for maintaining neuronal function. We investigated chrysophanol's effects on glutamate-induced hippocampal neuronal cell death...
June 23, 2017: Pharmacology
https://www.readbyqxmd.com/read/28634116/succinate-induced-neuronal-mitochondrial-fission-and-hexokinase-ii-malfunction-in-ischemic-stroke-therapeutical-effects-of-kaempferol
#17
Bin Wu, Hong Luo, Xu Zhou, Cai-Yi Cheng, Lin Lin, Bao-Lin Liu, Kang Liu, Ping Li, Hua Yang
Mitochondrial dysfunction is known as one of causative factors in ischemic stroke, leading to neuronal cell death. The present work was undertaken to investigate whether succinate induces neuron apoptosis by regulating mitochondrial morphology and function. In neurons, oxygen-glucose deprivation induced succinate accumulation due to the reversal of succinate dehydrogenase (SDH) activation, leading to mitochondrial fission. Kaempferol inhibited mitochondrial fission and maintained mitochondrial HK-II through activation of Akt, and thereby protected neurons from succinate-mediated ischemi injury...
June 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28632757/molecular-mechanism-of-drp1-assembly-studied-in-vitro-by-cryo-electron-microscopy
#18
Kaustuv Basu, Driss Lajoie, Tristan Aumentado-Armstrong, Jin Chen, Roman I Koning, Blaise Bossy, Mihnea Bostina, Attila Sik, Ella Bossy-Wetzel, Isabelle Rouiller
Mitochondria are dynamic organelles that continually adapt their morphology by fusion and fission events. An imbalance between fusion and fission has been linked to major neurodegenerative diseases, including Huntington's, Alzheimer's, and Parkinson's diseases. A member of the Dynamin superfamily, dynamin-related protein 1 (DRP1), a dynamin-related GTPase, is required for mitochondrial membrane fission. Self-assembly of DRP1 into oligomers in a GTP-dependent manner likely drives the division process. We show here that DRP1 self-assembles in two ways: i) in the presence of the non-hydrolysable GTP analog GMP-PNP into spiral-like structures of ~36 nm diameter; and ii) in the presence of GTP into rings composed of 13-18 monomers...
2017: PloS One
https://www.readbyqxmd.com/read/28630156/apoptotic-foci-at-mitochondria-in-and-around-bax-pores
#19
REVIEW
Begoña Ugarte-Uribe, Ana J García-Sáez
The permeabilization of the mitochondrial outer membrane by Bax and Bak during apoptosis is considered a key step and a point of no return in the signalling pathway. It is always closely related to the reorganization of mitochondrial cristae that frees cytochrome c to the intermembrane space and to massive mitochondrial fragmentation mediated by the dynamin-like protein Drp1. Despite multiple evidence in favour of a functional link between these processes, the molecular mechanisms that connect them and their relevance for efficient apoptosis signalling remain obscure...
August 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28624623/mitochondrial-fission-forms-a-positive-feedback-loop-with-cytosolic-calcium-signaling-pathway-to-promote-autophagy-in-hepatocellular-carcinoma-cells
#20
Qichao Huang, Haiyan Cao, Lei Zhan, Xiacheng Sun, Gang Wang, Jibin Li, Xu Guo, Tingting Ren, Zhe Wang, Yinghua Lyu, Bingrong Liu, Jiaze An, Jinliang Xing
Both mitochondrial morphology and the level of cytosolic calcium [Ca(2+)]c are actively changed and play critical roles in a number of malignancies. However, whether communications existed between these two processes to ingeniously control the malignant phenotype are far from clear. We investigated the reciprocal regulation between mitochondrial fission and cytosolic calcium signaling in human hepatocellular carcinoma (HCC) cells. Furthermore, the underlying molecular mechanisms and the synergistic effect on autophagy were explored...
June 15, 2017: Cancer Letters
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