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TonE and mitochondria

Chin-Chang Chen, Tzung-Yan Lee, Ching-Fai Kwok, Yung-Pei Hsu, Kuang-Chung Shih, Yan-Jie Lin, Low-Tone Ho
Over activity of cannabinoid receptor type 1 (CB1R) plays a key role in increasing the incidence of obesity-induced non-alcoholic fatty liver disease. Tissue proteome analysis has been applied to investigate the bioinformatics regarding the mode of action and therapeutic mechanism. The aim of this study was to explore the potential pathways altered with CB1R in obesity-induced fatty liver. Male C57BL/6 mice were fed either a standard chow diet (STD) or a high-fat diet (HFD) with or without 1-week treatment of CB1R inverse agonist AM251 at 5 mg/kg...
January 2017: Proteomics
Camilla F Wenceslau, Cameron G McCarthy, R Clinton Webb
The major pathophysiological characteristic of systemic inflammatory response syndrome (SIRS) and sepsis is the loss of control of vascular tone and endothelial barrier dysfunction. These changes are attributed to pro-inflammatory mediators. It has been proposed that in patients and rats without infection, cell components from damaged tissue are the primary instigators of vascular damage. Mitochondria share several characteristics with bacteria, and when fragments of mitochondria are released into the circulation after injury, they are recognized by the innate immune system...
2016: Frontiers in Immunology
Saška Lipovšek, Tone Novak, Franc Janžekovič, Nina Weiland, Gerd Leitinger
During winter, cave cricket larvae undergo dormancy in subterranean habitats; this dormancy is termed diapause in second year Troglophilus cavicola larvae because they mature during this time, and termed quiescence in T. neglectus, because they mature after dormancy. Here we used electron microscopy to analyze ultrastructural changes in the epithelial cells in the Malpighian tubules (MTs) of T. cavicola during diapause, in order to compare them with previous findings on T. neglectus. Moreover, the autophagosomes were studied with immunofluorescence microscopy in both species...
2016: PloS One
David W Busija, Ibolya Rutkai, Somhrita Dutta, Prasad V Katakam
Mitochondria not only produce energy in the form of ATP to support the activities of cells comprising the neurovascular unit, but mitochondrial events, such as depolarization and/or ROS release, also initiate signaling events which protect the endothelium and neurons against lethal stresses via pre-/postconditioning as well as promote changes in cerebral vascular tone. Mitochondrial depolarization in vascular smooth muscle (VSM), via pharmacological activation of the ATP-dependent potassium channels on the inner mitochondrial membrane (mitoKATP channels), leads to vasorelaxation through generation of calcium sparks by the sarcoplasmic reticulum and subsequent downstream signaling mechanisms...
2016: Comprehensive Physiology
H Almukhtar, M J Garle, P A Smith, R E Roberts
Statins induce acute vasorelaxation which may contribute to the overall benefits of statins in the treatment of cardiovascular disease. The mechanism underlying this relaxation is unknown. As statins have been shown to alter mitochondrial function, in this study we investigated the role of mitochondria in the relaxation to simvastatin. Relaxation of porcine coronary artery segments by statins was measured using isolated tissue baths. Mitochondrial activity was determined by measuring changes in rhodamine 123 fluorescence...
August 15, 2016: Toxicology and Applied Pharmacology
Dario R Lemos, Graham Marsh, Angela Huang, Gabriela Campanholle, Takahide Aburatani, Lan Dang, Ivan Gomez, Ken Fisher, Giovanni Ligresti, Janos Peti-Peterdi, Jeremy S Duffield
Pericytes are tissue-resident mesenchymal progenitor cells anatomically associated with the vasculature that have been shown to participate in tissue regeneration. Here, we tested the hypothesis that kidney pericytes, derived from FoxD1(+) mesodermal progenitors during embryogenesis, are necessary for postnatal kidney homeostasis. Diphtheria toxin delivery to FoxD1Cre::RsDTR transgenic mice resulted in selective ablation of >90% of kidney pericytes but not other cell lineages. Abrupt increases in plasma creatinine, blood urea nitrogen, and albuminuria within 96 h indicated acute kidney injury in pericyte-ablated mice...
December 1, 2016: American Journal of Physiology. Renal Physiology
Diorginis José Soares Ferreira, Anderson Apolônio da Silva Pedroza, Glauber Rude Feitoza Braz, Reginaldo Correia da Silva-Filho, Talitta Arruda Lima, Mariana Pinheiro Fernandes, Sonia Q Doi, Claudia Jacques Lagranha
Mitochondrial bioenergetics dysfunction has been postulated as an important mechanism associated to a number of cardiovascular diseases in adulthood. One of the hypotheses is that this is caused by the metabolic challenge generated by the mismatch between prenatal predicted and postnatal reality. Perinatal low-protein diet produces several effects that are manifested in the adult animal, including altered sympathetic tone, increased arterial blood pressure and oxidative stress in the brainstem. The majority of the studies related to nutritional programming postulates that the increased risk levels for non-communicable diseases are associated with the incompatibility between prenatal and postnatal environment...
April 21, 2016: Brain Research
Walmor C De Mello
The influence of intracellular angiotensin II on the regulation of potassium current and membrane potential of smooth muscle cells of mesenteric arteries and its relevance for the regulation of vascular tone was reviewed. The presence of components of the renin angiotensin system (RAS) in different cells of the cardiovascular system, was discussed including their presence in the nuclei and mitochondria. Emphasis was given to the opposite effects of intracellular and extracellular angiotensin II (Ang II) on the regulation of potassium current, membrane potential and contractility of vascular resistance vessels and its implication to vascular physiology and pathology and the possible role of epigenetic factors on the expression of angiotensin II (Ang II) and renin in vascular resistance vessels as well as its possible pathophysiological role in hypertension and other cardiovascular diseases...
April 2016: Peptides
Neta Gazit, Irena Vertkin, Ilana Shapira, Martin Helm, Edden Slomowitz, Maayan Sheiba, Yael Mor, Silvio Rizzoli, Inna Slutsky
The insulin-like growth factor-1 receptor (IGF-1R) signaling is a key regulator of lifespan, growth, and development. While reduced IGF-1R signaling delays aging and Alzheimer's disease progression, whether and how it regulates information processing at central synapses remains elusive. Here, we show that presynaptic IGF-1Rs are basally active, regulating synaptic vesicle release and short-term plasticity in excitatory hippocampal neurons. Acute IGF-1R blockade or transient knockdown suppresses spike-evoked synaptic transmission and presynaptic cytosolic Ca(2+) transients, while promoting spontaneous transmission and resting Ca(2+) level...
February 3, 2016: Neuron
Bryan A Wilson, Manisha Nautiyal, TanYa M Gwathmey, James C Rose, Mark C Chappell
Evidence for an intracellular renin-angiotensin system (RAS) in various cell organelles now includes the endoplasmic reticulum, nucleus and mitochondria (Mito). Indeed, angiotensin (Ang) AT1 and AT2 receptor subtypes were functionally linked to Mito respiration and nitric oxide production, respectively in previous studies. We undertook a biochemical analysis of the Mito RAS from male and female sheep kidney cortex. Mito -were isolated by differential centrifugation followed by a discontinuous Percoll gradient and were co-enriched in Mito membrane markers VDAC and ATP synthase, but not β-actin or cathepsin B...
December 23, 2015: American Journal of Physiology. Renal Physiology
Andreas Daiber, Fabio Di Lisa, Matthias Oelze, Swenja Kröller-Schön, Sebastian Steven, Eberhard Schulz, Thomas Münzel
Cardiovascular diseases are associated with and/or caused by oxidative stress. This concept has been proven by using the approach of genetic deletion of reactive species producing (pro-oxidant) enzymes as well as by the overexpression of reactive species detoxifying (antioxidant) enzymes leading to a marked reduction of reactive oxygen and nitrogen species (RONS) and in parallel to an amelioration of the severity of diseases. Likewise, the development and progression of cardiovascular diseases is aggravated by overexpression of RONS producing enzymes as well as deletion of antioxidant RONS detoxifying enzymes...
December 9, 2015: British Journal of Pharmacology
Jaclyn S Lerea, Laurence E Ring, Rim Hassouna, Angie C N Chong, Klara Szigeti-Buck, Tamas L Horvath, Lori M Zeltser
Although most adults can lose weight by dieting, a well-characterized compensatory decrease in energy expenditure promotes weight regain more than 90% of the time. Using mice with impaired hypothalamic leptin signaling as a model of early-onset hyperphagia and obesity, we explored whether this unfavorable response to weight loss could be circumvented by early intervention. Early-onset obesity was associated with impairments in the structure and function of brown adipose tissue mitochondria, which were ameliorated by weight loss at any age...
February 2016: Endocrinology
Carlo G Tocchetti, Brian A Stanley, Vidhya Sivakumaran, Djahida Bedja, Brian O'Rourke, Nazareno Paolocci, Sonia Cortassa, Miguel A Aon
In Type I diabetic (T1DM) patients, both peaks of hyperglycaemia and increased sympathetic tone probably contribute to impair systolic and diastolic function. However, how these stressors eventually alter cardiac function during T1DM is not fully understood. In the present study, we hypothesized that impaired mitochondrial energy supply and excess reactive oxygen species (ROS) emission is centrally involved in T1DM cardiac dysfunction due to metabolic/redox stress and aimed to determine the mitochondrial sites implicated in these alterations...
October 2015: Clinical Science (1979-)
J Benjamin Kacerovsky, K K Murai
Astrocytes are major non-neuronal cell types in the central nervous system that regulate a variety of processes in the brain including synaptic transmission, neurometabolism, and cerebrovasculature tone. Recent discoveries have revealed that astrocytes perform very specialized and heterogeneous roles in brain homeostasis and function. Exactly how astrocytes fulfill such diverse roles in the brain remains to be fully understood and is an active area of research. In this review, we focus on the complex subcellular anatomical features of protoplasmic gray matter astrocytes in the mature, healthy brain that likely empower these cells with the ability to detect and respond to changes in neuronal and synaptic activity...
May 26, 2016: Neuroscience
Maksym I Harhun
Vasomotion is the rhythmical changes in vascular tone of various blood vessels. It was proposed that in rabbit portal vein (RPV) the spontaneous contractile activity is driven by vascular interstitial cells (VICs), since RPV VICs generate rhythmical changes in intracellular Ca(2+) concentration ([Ca(2+)]i) associated with membrane depolarisation in these cells. In this work, using confocal imaging in Fluo-3 loaded RPV VICs we studied if generation of rhythmical [Ca(2+)]i changes is affected when Ca(2+) handling by mitochondria is compromised...
September 2015: Cell Calcium
Linda S Hoffmann, Christopher J Larson, Alexander Pfeifer
The second messenger cyclic guanosine monophosphate (cGMP) is a key mediator in physiological processes such as vascular tone, and its essential involvement in pathways regulating metabolism has been recognized in recent years. Here, we focus on the fundamental role of cGMP in brown adipose tissue (BAT) differentiation and function. In contrast to white adipose tissue (WAT), which stores energy in the form of lipids, BAT consumes energy stored in lipids to generate heat. This so-called non-shivering thermogenesis takes place in BAT mitochondria, which express the specific uncoupling protein 1 (UCP1)...
2016: Handbook of Experimental Pharmacology
Véronique Brault, Arnaud Duchon, Caroline Romestaing, Ignasi Sahun, Stéphanie Pothion, Mona Karout, Christelle Borel, Doulaye Dembele, Jean-Charles Bizot, Nadia Messaddeq, Andrew J Sharp, Damien Roussel, Stylianos E Antonarakis, Mara Dierssen, Yann Hérault
The trisomy of human chromosome 21 (Hsa21), which causes Down syndrome (DS), is the most common viable human aneuploidy. In contrast to trisomy, the complete monosomy (M21) of Hsa21 is lethal, and only partial monosomy or mosaic monosomy of Hsa21 is seen. Both conditions lead to variable physiological abnormalities with constant intellectual disability, locomotor deficits, and altered muscle tone. To search for dosage-sensitive genes involved in DS and M21 phenotypes, we created two new mouse models: the Ts3Yah carrying a tandem duplication and the Ms3Yah carrying a deletion of the Hspa13-App interval syntenic with 21q11...
March 2015: PLoS Genetics
John T Hancock, Matthew Whiteman
Signaling in cells involving reactive compounds is well established. Reactive oxygen species (ROS) and nitric oxide (NO) are known to be extremely influential in the control of a range of physiological responses in many organisms, from animals to plants. Often, their generation is triggered in reaction to stress, and it is common for ROS and NO metabolism to interact to give a coordinated response. Recently, hydrogen sulfide (H2 S) has also been found to be an important signaling molecule, being shown to be involved in vascular tone in animals...
February 2016: Annals of the New York Academy of Sciences
Richard T Clements, Dmitry Terentyev, Frank W Sellke
Small- and large-conductance Ca(2+)-activated K(+)channels (SKCa and BKCa, respectively) may be important targets for therapeutic interventions in a variety of cardiac conditions. In cardiomyocytes, BKCa channels are localized to mitochondria where they beneficially modulate reactive oxygen species, mitochondrial Ca(2+), and respiration. In vascular smooth muscle cells, BKCa channels regulate vascular tone and promote vasodilation. Activation of BKCa channels has demonstrated significant cardioprotection following ischemic injury, including improved function and reduced infarct size...
2015: Circulation Journal: Official Journal of the Japanese Circulation Society
Amy M Palubinsky, Jeannette N Stankowski, Alixandra C Kale, Simona G Codreanu, Robert J Singer, Daniel C Liebler, Gregg D Stanwood, BethAnn McLaughlin
AIMS: Determine the mechanism by which C-terminus of HSC70-interacting protein (CHIP) induction alters neuronal survival under conditions of mitochondrial stress induced by oxygen glucose deprivation. RESULTS: We report that animals deficient in the E3 ubiquitin ligase, CHIP, have high baseline levels of central nervous system protein oxidation and lipid peroxidation, reduced antioxidant defenses, and decreased energetic status. Stress-associated molecules typically linked to Parkinson's disease such as the mitochondrial kinase, PTEN-inducible putative kinase 1 (PINK1), and another E3 ligase, Parkin, are upregulated in brains from CHIP knockout (KO) animals...
August 20, 2015: Antioxidants & Redox Signaling
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