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neutrophil mitochondria

M A Chelombitko, O A Averina, T V Vasilyeva, O Yu Pletiushkina, E N Popova, A V Fedorov, B V Chernyak, V S Shishkina, O P Ilinskaya
The therapeutic effect of mitochondria-targeted antioxidant 10-(6´-plastoquinonyl)decyltriphenylphosphonium bromide (SkQ1) in experimental models of acute inflammation and wound repair has been shown earlier. It was suggested that the antiinflammatory activity of SkQ1 is related to its ability to suppress inflammatory activation of the vascular endothelium and neutrophil migration into tissues. Here, we demonstrated that SkQ1 inhibits activation of mast cells (MCs) followed by their degranulation and histamine release in vivo and in vitro...
December 2017: Biochemistry. Biokhimii︠a︡
Manoj K Pandey, Gregory A Grabowski, Jörg Köhl
The complement system is well appreciated for its role as an important effector of innate immunity that is activated by the classical, lectin or alternative pathway. C5a is one important mediator of the system that is generated in response to canonical and non-canonical C5 cleavage by circulating or cell-derived proteases. In addition to its function as a chemoattractant for neutrophils and other myeloid effectors, C5a and its sister molecule C3a have concerted roles in cell homeostasis and surveillance. Through activation of their cognate G protein coupled receptors, C3a and C5a regulate multiple intracellular pathways within the mitochondria and the lysosomal compartments that harbor multiple enzymes critical for protein, carbohydrate and lipid metabolism...
February 22, 2018: Seminars in Immunology
Jiaqi Gu, Lingchun Luo, Qian Wang, Songfan Yan, Jing Lin, Dan Li, Bingbing Cao, Hongxia Mei, Binyu Ying, Lu Bin, Fang Gao Smith, Sheng-Wei Jin
Inflammation always accompanies infection during sepsis. Mitochondrial dysfunction and the role of reactive oxygen species (ROS) produced by mitochondria have been proposed in the pathogenesis of sepsis. Maresins have protective and resolving effects in experimental models of infection. In the present study, we investigated the effects of maresin 1 (MaR1) on mitochondrial function in cecal ligation and puncture (CLP)-induced sepsis and sepsis patients to identify mechanisms underlying maresin 1-mediated stimulation of ROS in mitochondria...
February 21, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Koichi Oshima, Norikazu Saiki, Michihiro Tanaka, Hiromi Imamura, Akira Niwa, Ayako Tanimura, Ayako Nagahashi, Akiyoshi Hirayama, Keisuke Okita, Akitsu Hotta, Shuichi Kitayama, Mitsujiro Osawa, Shin Kaneko, Akira Watanabe, Isao Asaka, Wataru Fujibuchi, Kohsuke Imai, Hiromasa Yabe, Yoshiro Kamachi, Junichi Hara, Seiji Kojima, Masaru Tomita, Tomoyoshi Soga, Takafumi Noma, Shigeaki Nonoyama, Tatsutoshi Nakahata, Megumu K Saito
AK2 is an adenylate phosphotransferase that localizes at the intermembrane spaces of the mitochondria, and its mutations cause a severe combined immunodeficiency with neutrophil maturation arrest named reticular dysgenesis (RD). Although the dysfunction of hematopoietic stem cells (HSCs) has been implicated, earlier developmental events that affect the fate of HSCs and/or hematopoietic progenitors have not been reported. Here, we used RD-patient-derived induced pluripotent stem cells (iPSCs) as a model of AK2-deficient human cells...
February 17, 2018: Biochemical and Biophysical Research Communications
Chun Li, Hong Sun, Guodong Xu, Kimberly D McCarter, Jiyu Li, William G Mayhan
Nicotine may contribute to the pathogenesis of cerebrovascular disease via the generation of reactive oxygen species (ROS). Overproduction of ROS leads to brain damage by intensifying post-ischemic inflammation. Our goal was to determine the effect of Mito-Tempo, a mitochondria-targeted antioxidant, on ischemic brain damage and post-ischemic inflammation during chronic exposure to nicotine. Male Sprague-Dawley rats were divided into four groups: control, nicotine, Mito-Tempo-treated control, and Mito-Tempo-treated nicotine...
February 8, 2018: Journal of Applied Physiology
Björn Ingelsson, Daniel Söderberg, Tobias Strid, Anita Söderberg, Ann-Charlotte Bergh, Vesa Loitto, Kourosh Lotfi, Mårten Segelmark, Giannis Spyrou, Anders Rosén
Circulating mitochondrial DNA (mtDNA) is receiving increasing attention as a danger-associated molecular pattern in conditions such as autoimmunity, cancer, and trauma. We report here that human lymphocytes [B cells, T cells, natural killer (NK) cells], monocytes, and neutrophils derived from healthy blood donors, as well as B cells from chronic lymphocytic leukemia patients, rapidly eject mtDNA as web filament structures upon recognition of CpG and non-CpG oligodeoxynucleotides of class C. The release was quenched by ZnCl2 , independent of cell death (apoptosis, necrosis, necroptosis, autophagy), and continued in the presence of TLR9 signaling inhibitors...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
Liu-Long Zhu, Mao-Qiang Li, Fan He, Shao-Bo Zhou, Wu Jiang
BACKGROUND/AIMS: Spinal cord injury (SCI) is a common and devastating disease, which results in systemic inflammatory response syndrome and secondary lung injury. Mitochondrial dysfunction and inflammation are closely related to lung injury in diverse disease models. No studies have demonstrated the effects of mitochondrial targeted peptide SS-31 in a mouse model of SCI-induced lung injury. METHODS: Immediately after injury, mice in the treatment groups received a daily, single-dose intraperitoneal injection of SS-31 and for the next 2 days...
November 13, 2017: Cellular Physiology and Biochemistry
Arnold N Onyango
Insulin resistance contributes to the development of diabetes and cardiovascular dysfunctions. Recent studies showed that elevated singlet oxygen-mediated lipid peroxidation precedes and predicts diet-induced insulin resistance (IR), and neutrophils were suggested to be responsible for such singlet oxygen production. This review highlights literature suggesting that insulin-responsive cells such as endothelial cells, hepatocytes, adipocytes, and myocytes also produce singlet oxygen, which contributes to insulin resistance, for example, by generating bioactive aldehydes, inducing endoplasmic reticulum (ER) stress, and modifying mitochondrial DNA...
2017: Oxidative Medicine and Cellular Longevity
Stephen R Thom, Veena M Bhopale, Kevin Yu, Weiliang Huang, Maureen A Kane, David J Margolis
Microparticles are lipid bilayer-enclosed vesicles produced by cells under oxidative stress. MP production is elevated in patients with diabetes, but the underlying cellular mechanisms are poorly understood. We hypothesized that raising glucose above the physiological level of 5.5 mm would stimulate leukocytes to produce MPs and activate the nucleotide-binding domain, leucine-rich repeat pyrin domain-containing 3 (NLRP3) inflammasome. We found that when incubated in buffer with up to 20 mm glucose, human and murine neutrophils, but not monocytes, generate progressively more MPs with high interleukin (IL)-1β content...
November 3, 2017: Journal of Biological Chemistry
Zhi Qiao, Johannes Greven, Klemens Horst, Roman Pfeifer, Philipp Kobbe, Hans-Christoph Pape, Frank Hildebrand
The process of fracture healing is complex and requires an interaction of multiple organ systems. Cell-cell communication is known to be very important during this process. Extracellular vesicle (EVs) are small membranous vesicles generated from a variety of cells. Proteins, RNAs, small molecules and mitochondria DNA were found to be transported among cells through EVs. EV-based crosstalk represents a substantial cell-cell communication pattern, that can both interact with cells through molecular surfaces, and transfer molecules to cells...
September 27, 2017: Shock
Driss El Kebir, Everton de Oliveira Lima Dos Santos, Soukaina Mansouri, Meriem Sekheri, János G Filep
Accumulating evidence indicates development of local extracellular acidosis in inflamed tissues in response to infection and tissue injury. Activation of infiltrating neutrophils contributes to a transient decrease in pH, which, in turn, triggers innate immunity. In this study, we investigated the impact of extracellular acidosis on neutrophil apoptosis, a critical determinant of the outcome of the inflammatory response and analyzed the underlying signaling pathways. Culture of human isolated neutrophils in mildly acidotic conditions (pH 6...
December 2017: Journal of Leukocyte Biology
Stefania Camastra, Alessandra Vitali, Marco Anselmino, Amalia Gastaldelli, Rosario Bellini, Rossana Berta, Ilenia Severi, Simona Baldi, Brenno Astiarraga, Giorgio Barbatelli, Saverio Cinti, Ele Ferrannini
Obesity is characterized by insulin-resistance (IR), enhanced lipolysis, and ectopic, inflamed fat. We related the histology of subcutaneous (SAT), visceral fat (VAT), and skeletal muscle to the metabolic abnormalities, and tested their mutual changes after bariatric surgery in type 2 diabetic (T2D) and weight-matched non-diabetic (ND) patients. We measured IR (insulin clamp), lipolysis ((2)H5-glycerol infusion), ß-cell glucose-sensitivity (ß-GS, mathematical modeling), and VAT, SAT, and rectus abdominis histology (light and electron microscopy)...
August 21, 2017: Scientific Reports
Minna E Kubin, Lars Hellberg, Riitta Palatsi
Bullous pemphigoid (BP) is the most common of pemphigoid diseases caused by autoantibodies against the structures of dermoepidermal junction followed by complement activation, innate immune cell infiltration, neutrophil proteinase secretion and subepidermal blister formation. The first-line treatment of BP is topical and systemic glucocorticoids (GC). Regulation of the immune system and inflammatory cells is the main target of GC actions. GCs act through genomic and non-genomic mechanisms. The human glucocorticoid receptor (GR) mediates most of the biologic effects of GC: cytosolic GR binds GCs and is capable to bind to glucocorticoid response elements in DNA and either transactivate or transrepress genes depending on the tissue and cell type...
December 2017: Experimental Dermatology
Ilya A Demyanenko, Vlada V Zakharova, Olga P Ilyinskaya, Tamara V Vasilieva, Artem V Fedorov, Vasily N Manskikh, Roman A Zinovkin, Olga Yu Pletjushkina, Boris V Chernyak, Vladimir P Skulachev, Ekaterina N Popova
Oxidative stress is widely recognized as an important factor in the delayed wound healing in diabetes. However, the role of mitochondrial reactive oxygen species in this process is unknown. It was assumed that mitochondrial reactive oxygen species are involved in many wound-healing processes in both diabetic humans and animals. We have applied the mitochondria-targeted antioxidant 10-(6'-plastoquinonyl)decyltriphenylphosphonium (SkQ1) to explore the role of mitochondrial reactive oxygen species in the wound healing of genetically diabetic mice...
2017: Oxidative Medicine and Cellular Longevity
Carlos Pérez-Sánchez, María Ángeles Aguirre, Patricia Ruiz-Limón, María Carmen Ábalos-Aguilera, Yolanda Jiménez-Gómez, Iván Arias-de la Rosa, Antonio Rodriguez-Ariza, Lucía Fernández-Del Río, José Antonio González-Reyes, Pedro Segui, Eduardo Collantes-Estévez, Nuria Barbarroja, Francisco Velasco, Savino Sciascia, Irene Cecchi, María José Cuadrado, José Manuel Villalba, Chary López-Pedrera
OBJECTIVE: Antiphospholipid syndrome (APS) leukocytes exhibit an oxidative perturbation, directly linked to alterations in mitochondrial dynamics and metabolism. This disturbance is related to the patients' prothrombotic status and can be prevented by in vitro treatment with coenzyme Q10. Our aim was to investigate short-term effects of in vivo ubiquinol (reduced coenzyme Q10 [Qred]) supplementation on markers related to inflammation and thrombosis in APS through a prospective, randomized, crossover, placebo-controlled trial...
October 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
Ying Wang, Wei Wang, Nan Wang, Alan R Tall, Ira Tabas
RATIONALE: Mitochondrial oxidative stress (mitoOS) has been shown to be increased in various cell types in human atherosclerosis and with aging. However, the role of cell type-specific mitoOS in atherosclerosis in the setting of advanced age and the molecular mechanisms remains to be determined in vivo. OBJECTIVE: The aim of this study was to examine the role of myeloid cell mitoOS in atherosclerosis in aged mice. APPROACH AND RESULTS: Lethally irradiated low-density lipoprotein receptor-deficient mice ( Ldlr -/- ) were reconstituted with bone marrow from either wild-type or mitochondrial catalase (mCAT) mice...
August 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
Lydia Renner, Stefan Kahlert, Tanja Tesch, Erik Bannert, Jana Frahm, Anikó Barta-Böszörményi, Jeannette Kluess, Susanne Kersten, Peter Schönfeld, Hermann-Josef Rothkötter, Sven Dänicke
The aim of the present study was to examine the role of chronic deoxynivalenol (DON) exposition on the liver morphology and function in combination with pre- and post-hepatic lipopolysaccharide (LPS) stress in young pigs fed for 4 weeks with a DON-contaminated diet (4.59 mg/kg feed). At the end of the experiment, LPS (7.5 μg/kg BW) was administered for 1 h pre-hepatically (Vena portae hepatis) or post-hepatically (Vena jugularis). Liver morphology was macroscopically checked and showed haemorrhage in all LPS groups, significantly higher relative liver weights, accompanied by marked oedema in the gallbladder wall...
August 2017: Mycotoxin Research
M A Chelombitko, O A Averina, T V Vasil'eva, E E Dvorianinova, M V Egorov, O Yu Pletjushkina, E N Popova, A V Fedorov, V P Romashchenko, O P Ilyinskaya
The effect of mitochondria-targeted antioxidant 10-(6'-plastoquinonyl) decyltriphenylphosphonium bromide (SkQ1) and its fragment dodecyltriphenylphosphonium (C12TPP), weak uncouplers of respiration and oxidative phosphorylation, was studied using a mouse model of carrageenan-induced acute inflammation in the subcutaneous air pouch. In our model, SkQ1 demonstrated a strong anti-inflammatory effect that manifested in a decrease in the absolute number of inflammatory cells, mainly neutrophils, and their relative number in parallel with an increase in macrophages and mast cell content in the inflammatory exudate...
April 2017: Bulletin of Experimental Biology and Medicine
Weifeng Yao, Haobo Li, Gangjian Luo, Xiang Li, Chaojin Chen, Dongdong Yuan, Xinjin Chi, Zhengyuan Xia, Ziqing Hei
BACKGROUND: Postoperative acute lung injury (ALI) is a severe complication after liver transplantation, which severely affects postoperative patients' survival. The underlying mechanism is largely unknown and effective treatment limited. We explored the role of serpin protease inhibitor B1 (SERPINB1), a potent inhibitor of neutrophil serine proteases, in ALI in liver transplantation and its interplay with signal transducer and activator of transcription 3 (STAT3) and heme oxygenase-1 (HO-1)...
April 17, 2017: Free Radical Biology & Medicine
Ahmed Khairallah, Abo-Alela Farag, Dina Johar, Larry Bernstein
The dynamics of cellular metabolism involves rapid interactions between proteins and nucleic acids, proteins and proteins, and signaling. These involve the interactions with respect to the sulfur bond, noncovalent electrostatic interactions, protein structure stabilization and protein-ligand binding, weak electrostatic interactions in proteins, oxygen radicals that initiate a change in conformation and a chain of events. We review a development in molecular medicine that is a very promising work in progress...
April 17, 2017: Journal of Cellular Biochemistry
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