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https://www.readbyqxmd.com/read/29351723/mitochondrial-uncoupling-proteins-subtle-regulators-of-cellular-redox-signaling
#1
Petr Jezek, Blanka Holendová, Keith D Garlid, Martin Jaburek
SIGNIFICANCE: Mitochondria are the energetic, metabolic, redox and information signaling centers of the cell. Substrate pressure, mitochondrial network dynamics and cristae morphology state are integrated by the protonmotive force Δp or its potential component, ΔΨ, which are attenuated by proton backflux into the matrix, termed uncoupling. The mitochondrial uncoupling proteins (UCP1-5) play an eminent role in the regulation of each of the above aspects, being involved in numerous physiological events including redox signaling...
January 19, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29348374/-neurologic-abnormalities-in-myalgic-encephalomyelitis-chronic-fatigue-syndrome-a-review
#2
Anthony L Komaroff, Ryosuke Takahashi, Takashi Yamamura, Masanori Sawamura
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an illness characterized by fatigue lasting for at least six months, post-exertional malaise, unrefreshing sleep, cognitive impairment and orthostatic intolerance. ME/CFS has been a controversial illness because it is defined exclusively by subjective complaints. However, recent studies of neuroimaging as well as analysis of blood markers, energy metabolism and mitochondrial function have revealed many objective biological abnormalities. Specifically, it is suspected that the symptoms of ME/CFS may be triggered by immune activation - either inside or outside the brain - through release of inflammatory cytokines...
January 2018: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/29348263/phosphoinositide-3-kinase-gamma-inhibition-protects-from-anthracycline-cardiotoxicity-and-reduces-tumor-growth
#3
Mingchuan Li, Valentina Sala, Maria Chiara De Santis, James Cimino, Paola Cappello, Nicola Pianca, Anna Di Bona, Jean Piero Margaria, Miriam Martini, Edoardo Lazzarini, Flora Pirozzi, Luca Rossi, Irene Franco, Julia Bornbaum, Jacqueline Heger, Susanne Rohrbach, Alessia Perino, Carlo G Tocchetti, Braulio H F Lima, Mauro M Teixeira, Paolo E Porporato, Rainer Schulz, Annalisa Angelini, Marco Sandri, Pietro Ameri, Sebastiano Sciarretta, Roberto César P Lima-Júnior, Marco Mongillo, Tania Zaglia, Fulvio Morello, Francesco Novelli, Emilio Hirsch, Alessandra Ghigo
Background -Anthracyclines, such as doxorubicin (DOX), are potent anti-cancer agents for the treatment of solid tumors and hematological malignancies. However, their clinical use is hampered by cardiotoxicity. This study sought to investigate the role of PI3Kγ in DOX-induced cardiotoxicity and the potential cardio-protective and anti-cancer effects of PI3Kγ inhibition. Methods -Mice expressing a kinase-inactive PI3Kγ or receiving PI3Kγ selective inhibitors were subjected to chronic DOX treatment. Cardiac function was analyzed by echocardiography and DOX-mediated signaling was assessed in whole hearts or in isolated cardiomyocytes...
January 18, 2018: Circulation
https://www.readbyqxmd.com/read/29348254/circulating-platelets-as-mediators-of-immunity-inflammation-and-thrombosis
#4
REVIEW
Milka Koupenova, Lauren Clancy, Heather A Corkrey, Jane E Freedman
Platelets, non-nucleated blood components first described over 130 years ago, are recognized as the primary cell regulating hemostasis and thrombosis. The vascular importance of platelets has been attributed to their essential role in thrombosis, mediating myocardial infarction, stroke, and venous thromboembolism. Increasing knowledge on the platelets' role in the vasculature has led to many advances in understanding not only how platelets interact with the vessel wall but also how they convey changes in the environment to other circulating cells...
January 19, 2018: Circulation Research
https://www.readbyqxmd.com/read/29348018/myocardial-inflammation-predicts-remodeling-and-neuroinflammation-after-myocardial-infarction
#5
James T Thackeray, Henri C Hupe, Yong Wang, Jens P Bankstahl, Georg Berding, Tobias L Ross, Johann Bauersachs, Kai C Wollert, Frank M Bengel
BACKGROUND: The local inflammatory tissue response after acute myocardial infarction (MI) determines subsequent healing. Systemic interaction may induce neuroinflammation as a precursor to neurodegeneration. OBJECTIVES: This study sought to assess the influence of MI on cardiac and brain inflammation using noninvasive positron emission tomography (PET) of the heart-brain axis. METHODS: After coronary artery ligation or sham surgery, mice (n = 49) underwent serial whole-body PET imaging of the mitochondrial translocator protein (TSPO) as a marker of activated macrophages and microglia...
January 23, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29345056/for-when-bacterial-infections-persist-toll-like-receptor-inducible-direct-antimicrobial-pathways-in-macrophages
#6
REVIEW
Claudia J Stocks, Mark A Schembri, Matthew J Sweet, Ronan Kapetanovic
Macrophages are linchpins of innate immunity, responding to invading microorganisms by initiating coordinated inflammatory and antimicrobial programs. Immediate antimicrobial responses, such as NADPH-dependent reactive oxygen species (ROS), are triggered upon phagocytic receptor engagement. Macrophages also detect and respond to microbial products through pattern recognition receptors (PRRs), such as TLRs. TLR signaling influences multiple biological processes including antigen presentation, cell survival, inflammation, and direct antimicrobial responses...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29342113/mitochondria-oxidative-stress-and-the-kynurenine-system-with-a-focus-on-ageing-and-neuroprotection
#7
REVIEW
Katalin Sas, Elza Szabó, László Vécsei
In this review, the potential causes of ageing are discussed. We seek to gain insight into the main physiological functions of mitochondria and discuss alterations in their function and the genome, which are supposed to be the central mechanisms in senescence. We conclude by presenting the potential modulating role of the kynurenine pathway in the ageing processes. Mitochondrial dynamics are supposed to have important physiological roles in maintaining cell homeostasis. During ageing, a decrease in mitochondrial dynamics was reported, potentially compromising the function of mitochondria...
January 17, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29340618/mitochondrial-toxicity
#8
Joel N Meyer, Jessica H Hartman, Danielle F Mello
Recent decades have seen a rapid increase in reported toxic effects of drugs and pollutants on mitochondria. Researchers have also documented many genetic differences leading to mitochondrial diseases, currently reported to affect ∼1 person in 4,300, creating a large number of potential gene-environment interactions in mitochondrial toxicity. We briefly review this history, and then highlight cutting-edge areas of mitochondrial research including the role of mitochondrial reactive oxygen species in signaling; increased understanding of fundamental biological processes involved in mitochondrial homeostasis (DNA maintenance and mutagenesis, mitochondrial stress response pathways, fusion and fission, autophagy and biogenesis, and exocytosis); systemic effects resulting from mitochondrial stresses in specific cell types; mitochondrial involvement in immune function; the growing evidence of long-term effects of mitochondrial toxicity; mitochondrial-epigenetic cross-talk; and newer approaches to test chemicals for mitochondrial toxicity...
January 11, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29338093/longitudinal-profiles-of-metabolism-and-bioenergetics-associated-with-innate-immune-hormonal-inflammatory-responses-and-amino-acid-kinetics-in-severe-sepsis-and-systemic-inflammatory-response-syndrome-in-children
#9
Anna Maria Spanaki, Theonymfi Tavladaki, Helen Dimitriou, Andrey V Kozlov, J Catharina Duvigneau, Eftychia Meleti, Adelheid Weidinger, Evangelos Papakonstantinou, George Briassoulis
BACKGROUND: Experimental data indicate that sepsis influences the mitochondrial function and metabolism. We aim to investigate longitudinal bioenergetic, metabolic, hormonal, amino-acid, and innate immunity changes in children with sepsis. METHODS: Sixty-eight children (sepsis, 18; systemic inflammatory response syndrome [SIRS], 23; healthy controls, 27) were enrolled. Plasma amino acids were determined by high-performance liquid chromatography (HPLC); flow-cytometry expressed as mean fluorescence intensity (MFI) of heat shock protein (HSP) levels from monocytes (m) and neutrophils (n); resistin, adiponectin, and extracellular (e) HSPs evaluated by ELISA; ATP levels in white blood cells by luciferase luminescent assay; lipid peroxidation products (TBARS) by colorimetric test; nitrite and nitrate levels by chemiluminescent assay; biliverdin reductase (BVR) activity by enzymatic assay; and energy-expenditure (EE) by E-COVX...
January 16, 2018: JPEN. Journal of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/29338042/a-pharmacological-screen-for-compounds-that-rescue-the-developmental-lethality-of-a-drosophila-atm-mutant
#10
Stacey A Rimkus, David A Wassarman
Ataxia-telangiectasia (A-T) is a neurodegenerative disease caused by mutation of the A-T mutated (ATM) gene. ATM encodes a protein kinase that is activated by DNA damage and phosphorylates many proteins, including those involved in DNA repair, cell cycle control, and apoptosis. Characteristic biological and molecular functions of ATM observed in mammals are conserved in Drosophila melanogaster. As an example, conditional loss-of-function ATM alleles in flies cause progressive neurodegeneration through activation of the innate immune response...
2018: PloS One
https://www.readbyqxmd.com/read/29331712/genetic-biomarkers-for-differential-diagnosis-of-major-depressive-disorder-and-bipolar-disorder-a-systematic-and-critical-review
#11
REVIEW
Itiana Castro Menezes, Cristiane von Werne Baes, Riccardo Lacchini, Mario Francisco Juruena
Depressive symptoms are present in the depressive mood state of bipolar disorder (BPD) and major depression disorder (MDD). Often, in clinical practice, BPD patients are misdiagnosed with MDD. Therefore, genetic biomarkers could contribute to the improvement of differential diagnosis between BPD and MDD. This systematic and critical review aimed to find in literature reliable genetic biomarkers that may show differences between BPD and MDD. This systematic review followed the PRISMA-P method. The terms used to search PubMed, Scopus, PsycINFO, and Web of Science were depress*, bipolar, diagnos*, genetic*, biomark*...
January 10, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29329795/omega-3-fatty-acids-and-adipose-tissue-biology
#12
REVIEW
Ondrej Kuda, Martin Rossmeisl, Jan Kopecky
This review provides evidence for the importance of white and brown adipose tissue (i.e. WAT and BAT) function for the maintenance of healthy metabolic phenotype and its preservation in response to omega-3 polyunsaturated fatty acids (omega-3 PUFA), namely in the context of diseased states linked to aberrant accumulation of body fat, systemic low-grade inflammation, dyslipidemia and insulin resistance. More specifically, the review deals with (i) the concept of immunometabolism, i.e. how adipose-resident immune cells and adipocytes affect each other and define the immune-metabolic interface; and (ii) the characteristic features of "healthy adipocytes" in WAT, which are relatively small fat cells endowed with a high capacity for mitochondrial oxidative phosphorylation, triacylglycerol/fatty acid (TAG/FA) cycling and de novo lipogenesis (DNL)...
January 9, 2018: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/29329794/redox-signals-and-macrophage-biology-for-the-upcoming-issue-of-molecular-aspects-of-medicine-on-signaling-by-reactive-oxygen-species
#13
REVIEW
Andreas Weigert, Andreas von Knethen, Dominik Fuhrmann, Nathalie Dehne, Bernhard Brüne
Macrophages are known for their versatile role in biology. They sense and clear structures that contain exogenous or endogenous pathogen-associated molecular patterns. This process is tightly linked to the production of a mixture of potentially harmful oxidants and cytokines. Their inherent destructive behavior is directed against foreign material or structures of 'altered self', which explains the role of macrophages during innate immune reactions and inflammation. However, there is also another side of macrophages when they turn into a tissue regenerative, pro-resolving, and healing phenotype...
January 9, 2018: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/29325869/microglial-activation-and-the-nitric-oxide-cgmp-pkg-pathway-underlie-enhanced-neuronal-vulnerability-to-mitochondrial-dysfunction-in-experimental-multiple-sclerosis
#14
Andrea Mancini, Michela Tantucci, Petra Mazzocchetti, Antonio de Iure, Valentina Durante, Lara Macchioni, Carmela Giampà, Alessandra Alvino, Lorenzo Gaetani, Cinzia Costa, Alessandro Tozzi, Paolo Calabresi, Massimiliano Di Filippo
During multiple sclerosis (MS), a close link has been demonstrated to occur between inflammation and neuro-axonal degeneration, leading to the hypothesis that immune mechanisms may promote neurodegeneration, leading to irreversible disease progression. Energy deficits and inflammation-driven mitochondrial dysfunction seem to be involved in this process. In this work we investigated, by the use of striatal electrophysiological field-potential recordings, if the inflammatory process associated with experimental autoimmune encephalomyelitis (EAE) is able to influence neuronal vulnerability to the blockade of mitochondrial complex IV, a crucial component for mitochondrial activity responsible of about 90% of total cellular oxygen consumption...
January 8, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29321620/lack-of-pink1-alters-glia-innate-immune-responses-and-enhances-inflammation-induced-nitric-oxide-mediated-neuron-death
#15
Liuke Sun, Ruifang Shen, Sandeep K Agnihotri, Yun Chen, Zhiwei Huang, Hansruedi Büeler
Neuroinflammation is involved in the pathogenesis of Parkinson's disease (PD) and other neurodegenerative disorders. We show that lack of PINK1- a mitochondrial kinase linked to recessive familial PD - leads to glia type-specific abnormalities of innate immunity. PINK1 loss enhances LPS/IFN-γ stimulated pro-inflammatory phenotypes of mixed astrocytes/microglia (increased iNOS, nitric oxide and COX-2, reduced IL-10) and pure astrocytes (increased iNOS, nitric oxide, TNF-α and IL-1β), while attenuating expression of both pro-inflammatory (TNF-α, IL-1β) and anti-inflammatory (IL-10) cytokines in microglia...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321276/ifn-regulatory-factor-3-balances-th1-and-t-follicular-helper-immunity-during-nonlethal-blood-stage-plasmodium-infection
#16
Kylie R James, Megan S F Soon, Ismail Sebina, Daniel Fernandez-Ruiz, Gayle Davey, Urijah N Liligeto, Arya Sheela Nair, Lily G Fogg, Chelsea L Edwards, Shannon E Best, Lianne I M Lansink, Kate Schroder, Jane A C Wilson, Rebecca Austin, Andreas Suhrbier, Steven W Lane, Geoffrey R Hill, Christian R Engwerda, William R Heath, Ashraful Haque
Differentiation of CD4+ Th cells is critical for immunity to malaria. Several innate immune signaling pathways have been implicated in the detection of blood-stage Plasmodium parasites, yet their influence over Th cell immunity remains unclear. In this study, we used Plasmodium-reactive TCR transgenic CD4+ T cells, termed PbTII cells, during nonlethal P. chabaudi chabaudi AS and P. yoelii 17XNL infection in mice, to examine Th cell development in vivo. We found no role for caspase1/11, stimulator of IFN genes, or mitochondrial antiviral-signaling protein, and only modest roles for MyD88 and TRIF-dependent signaling in controlling PbTII cell expansion...
January 10, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29317705/pneumolysin-induced-mitochondrial-dysfunction-leads-to-release-of-mitochondrial-dna
#17
Andreas Nerlich, Maren Mieth, Eleftheria Letsiou, Diana Fatykhova, Katja Zscheppang, Aki Imai-Matsushima, Thomas F Meyer, Lisa Paasch, Timothy J Mitchell, Mario Tönnies, Torsten T Bauer, Paul Schneider, Jens Neudecker, Jens C Rückert, Stephan Eggeling, Maria Schimek, Martin Witzenrath, Norbert Suttorp, Stefan Hippenstiel, Andreas C Hocke
Streptococcus pneumoniae (S.pn.) is the most common bacterial pathogen causing community acquired pneumonia. The pore-forming toxin pneumolysin (PLY) is the major virulence factor of S.pn. and supposed to affect alveolar epithelial cells thereby activating the immune system by liberation of danger-associated molecular patterns (DAMP). To test this hypothesis, we established a novel live-cell imaging based assay to analyse mitochondrial function and associated release of mitochondrial DNA (mtDNA) as DAMP in real-time...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29317664/human-cytomegalovirus-encoded-us9-targets-mavs-and-sting-signaling-to-evade-type-i-interferon-immune-responses
#18
Hyun Jin Choi, Areum Park, Sujin Kang, Eunhye Lee, Taeyun A Lee, Eun A Ra, Jiseon Lee, Sungwook Lee, Boyoun Park
Human cytomegalovirus (HCMV) has evolved sophisticated immune evasion mechanisms that target both the innate and adaptive immune responses. However, how HCMV encoded proteins are involved in this immune escape is not clear. Here, we show that HCMV glycoprotein US9 inhibits the IFN-β response by targeting the mitochondrial antiviral-signaling protein (MAVS) and stimulator of interferon genes (STING)-mediated signaling pathways. US9 accumulation in mitochondria attenuates the mitochondrial membrane potential, leading to promotion of MAVS leakage from the mitochondria...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29304412/developmental-toxicity-and-potential-mechanisms-of-pyraoxystrobin-to-zebrafish-danio-rerio
#19
Hui Li, Song Yu, Fangjie Cao, Chengju Wang, Mingqi Zheng, Xuefeng Li, Lihong Qiu
As a newly developed, highly efficient strobilurin fungicide, pyraoxystrobin has been reported to be highly toxic to some aquatic organisms. However, the toxicity of pyraoxystrobin to different life stages of fish and the potential underlying mechanisms are still unknown. Hence, in the present study, the acute toxicity of pyraoxystrobin to different life stages of zebrafish (embryo, larva, and adult) was assessed. The developmental toxicity of pyraoxystrobin to zebrafish embryos and its effects on gene transcription in the embryo were also investigated...
January 2, 2018: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/29303013/inhibition-of-plasma-kallikrein-kinin-system-to-alleviate-renal-injury-and-arthritis-symptoms-in-rats-with-adjuvant-induced-arthritis
#20
Jie Zhu, Hui Wang, Jingyu Chen, Wei Wei
BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Impairment of kidney functions in RA was observed. However, the mechanism of kidney injury of RA has not been clear. Plasma kallikrein-kinin system (KKS) was involved in inflammatory processes in kidney disease. AIM: This study aimed to explore the role of plasma KKS in immune reactions and kidney injury of RA. RESULTS: The paw of AA rats appeared to be swelling and redness, the arthritis index was significantly increased on the 18, 21 and 24 d after injection and secondary inflammation in multi-sites was observed...
January 5, 2018: Immunopharmacology and Immunotoxicology
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