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Antonietta Franco, Daniela Sorriento, Jessica Gambardella, Roberto Pacelli, Nella Prevete, Claudio Procaccini, Giuseppe Matarese, Bruno Trimarco, Guido Iaccarino, Michele Ciccarelli
The modern understanding of the G protein-coupled receptor kinase 2 has grown towards the definition of a stress protein, for its ability to rapidly compartmentalize within the cell in response to acute stimulation. Also, mitochondria can be regulated by GRK2 localization. We show that Ionizing Radiation (IR) exposure acutely damages mitochondria regarding mass, morphology, and respiration, with recovery in a framework of hours. This phenomenon is actively regulated by GRK2, whose overexpression results to be protective, and reciprocally, deletion accelerates degenerative processes...
December 2018: Cell Death Discovery
Massa Oi, Daniel Donner, Jason Peart, Belinda Beck, Lauren Wendt, John P Headrick, Eugene F du Toit
Statins are effective in management of dyslipidaemia, and a cornerstone of CVD prevention strategies. However, the impacts of their pleiotropic effects on other cardiovascular risk factors and myocardial responses to infarction are not well characterised. We hypothesised that pravastatin treatment in obesity improves lipid profiles, insulin-resistance and myocardial resistance to ischaemia/reperfusion (I/R) injury. Wistar rats were fed a control (C) chow or high carbohydrate and fat diet (HCFD) for 16 weeks with vehicle or pravastatin (prava 7...
March 1, 2018: European Journal of Pharmacology
Liming Yan, Yuanbo Qi, Xiaofang Huang, Caiting Yu, Lan Lan, Xiangyang Guo, Zihe Rao, Junjie Hu, Zhiyong Lou
Fusion of the outer mitochondrial membrane is mediated by the dynamin-like GTPase mitofusin (MFN). Here, we determined the structure of the minimal GTPase domain (MGD) of human MFN1 in complex with GDP-BeF3 - . The MGD folds into a canonical GTPase fold with an associating four-helix bundle, HB1, and forms a dimer. A potassium ion in the catalytic core engages GDP and BeF3 - (GDP-BeF3 - ). Enzymatic analysis has confirmed that efficient GTP hydrolysis by MFN1 requires potassium. Compared to previously reported MGD structures, the HB1 structure undergoes a major conformational change relative to the GTPase domains, as they move from pointing in opposite directions to point in the same direction, suggesting that a swing of the four-helix bundle can pull tethered membranes closer to achieve fusion...
February 26, 2018: Nature Structural & Molecular Biology
James E Glazer, Nicholas J Kelley, Narun Pornpattananangkul, Vijay A Mittal, Robin Nusslock
Most reward-related electroencephalogram (EEG) studies focus exclusively on the feedback-related negativity (FRN, also known as feedback negativity or FN, medial-frontal negativity or MFN, feedback error-related negativity or fERN, and reward positivity or RewP). This component is usually measured approximately 200-300 ms post-feedback at a single electrode in the frontal-central area (e.g., Fz or FCz). The present review argues that this singular focus on the FRN fails to leverage EEG's greatest strength, its temporal resolution, by underutilizing the rich variety of event-related potential (ERP) and EEG time-frequency components encompassing the wider temporal heterogeneity of reward processing...
February 15, 2018: International Journal of Psychophysiology
Sarah Verena Mayer, Karsten Rauss, Gilles Pourtois, Aiste Jusyte, Michael Schönenberg
Antisocial personality disorder is characterized by a stable, lifelong pattern of disregard for and violation of others' rights. Disruptions in the representation of fairness norms may represent a key mechanism in the development and maintenance of this disorder. Here, we investigated fairness norm considerations and reactions to their violations. To examine electrophysiological correlates, we assessed the medial frontal negativity (MFN), an event-related potential previously linked to violations of social expectancy and norms...
February 3, 2018: European Archives of Psychiatry and Clinical Neuroscience
Dennis K Fix, Justin P Hardee, Song Gao, Brandon N VanderVeen, Kandy T Velazquez, James A Carson
The IL-6 cytokine family activates intracellular signaling pathways through glycoprotein 130 (gp130), and this signaling has established regulatory roles in muscle glucose metabolism and proteostasis. Although the IL-6 family has been implicated as myokines regulating the muscle's metabolic response to exercise, gp130's role in mitochondrial quality control involving fission, fusion, mitophagy and biogenesis is not well understood. Therefore, we examined gp130's role in basal and exercise-trained muscle mitochondrial quality control...
February 1, 2018: Journal of Applied Physiology
Erkan Tuncay, Verda Bitirim, Yusuf Olgar, Aysegul Durak, Guy A Rutter, Belma Turan
Functional contribution of S(E)R-mitochondria coupling to normal cellular processes is crucial and any alteration in S(E)R-mitochondria axis may be responsible for the onset of diseases. Mitochondrial free Zn2+ level in cardiomyocytes ([Zn2+]Mit) is lower comparison to either its cytosolic or S(E)R level under physiological condition. However, there is little information about distribution of Zn2+-transporters on mitochondria and role of Zn2+-dependent mitochondrial-function associated with [Zn2+]Mit. Since we recently have shown how hyperglycemia (HG)-induced changes in ZIP7 and ZnT7 contribute to Zn2+-transport across S(E)R and contribute to S(E)R-stress in the heart, herein, we hypothesized that these transporters can also be localized to mitochondria and affect the S(E)R-mitochondria coupling, and thereby contribute to cellular Zn2+-muffling between S(E)R-mitochondria in HG-cells...
January 4, 2018: Mitochondrion
Thomas G. Wolf, Frank Paqué, Patrick Betz, Brita Willershausen, Benjamín Briseño-Marroquín
The root canal system morphology of the mandibular second molar was investigated by means of micro-computed tomography (μCT). The root canal configuration (RCC), foramina and accessory canals frequency of 93 mandibular second molars of an Egyptian sample were investigated by μCT scans. The RCC and main foramina number (MFN) are described by means of a four-digit system from coronal to apical. The most frequently observed RCCs in the mesial root were 2-2-1/1 (32.3%), 2-2-2/2 (28.0%), 1-1-1/1 (6.5%) and 2-1-1/1 (6...
June 18, 2017: Swiss Dental Journal
Ling Xiang, Yan Chen, Antao Chen, Fenghua Zhang, Fuming Xu, Baoxi Wang
The current study used event-related brain potentials (ERPs) to explore whether self-reported trait impulsivity in healthy individuals might be differentially related to proactive and reactive interference control. Participants with high and low impulsivity (HI and LI, respectively) performed a modified version of the prime-target interference task. Proactive interference control was induced in the mostly incongruent (MI) context and reactive interference control was induced in the mostly congruent (MC) context...
December 13, 2017: Brain Research
Sevan Mattie, Jan Riemer, Jeremy G Wideman, Heidi M McBride
Mitochondrial fusion occurs in many eukaryotes, including animals, plants, and fungi. It is essential for cellular homeostasis, and yet the underlying mechanisms remain elusive. Comparative analyses and phylogenetic reconstructions revealed that fungal Fzo1 and animal Mitofusin proteins are highly diverged from one another and lack strong sequence similarity. Bioinformatic analysis showed that fungal Fzo1 proteins exhibit two predicted transmembrane domains, whereas metazoan Mitofusins contain only a single transmembrane domain...
February 5, 2018: Journal of Cell Biology
Jun-Mo Kim, Kyu-Sang Lim, Kyung-Bo Ko, Youn-Chul Ryu
Here, we newly provided the parameters for estimating meat quality in live pigs using the muscle biopsy. The biopsied longissimus thoracis muscle was used to identify the muscle fibre characteristics (MFCs). Of the various MFCs in biopsied muscle, muscle fibre number (MFN) composition showed the greatest correlation with the MFCs in postmortem muscle (P<0.001). Moreover, the pigs cluster groups, based on the biopsied MFN composition, demonstrated statistically significant differences in meat quality traits such as muscle pH, drip loss, and meat colour (P<0...
March 2018: Meat Science
Moshi Song, Antonietta Franco, Julie A Fleischer, Lihong Zhang, Gerald W Dorn
Mitochondrial fusion and fission are critical to heart health; genetically interrupting either is rapidly lethal. To understand whether it is loss of, or the imbalance between, fusion and fission that underlies observed cardiac phenotypes, we engineered mice in which Mfn-mediated fusion and Drp1-mediated fission could be concomitantly abolished. Compared to fusion-defective Mfn1/Mfn2 cardiac knockout or fission-defective Drp1 cardiac knockout mice, Mfn1/Mfn2/Drp1 cardiac triple-knockout mice survived longer and manifested a unique pathological form of cardiac hypertrophy...
December 5, 2017: Cell Metabolism
Xiaofang Huang, Xin Zhou, Xiaoyu Hu, Amit S Joshi, Xiangyang Guo, Yushan Zhu, Quan Chen, William A Prinz, Junjie Hu
Mitochondria constantly divide and fuse. Homotypic fusion of the outer mitochondrial membranes requires the mitofusin (MFN) proteins, a family of dynamin-like GTPases. MFNs are anchored in the membrane by transmembrane (TM) segments, exposing both the N-terminal GTPase domain and the C-terminal tail (CT) to the cytosol. This arrangement is very similar to that of the atlastin (ATL) GTPases, which mediate fusion of endoplasmic reticulum (ER) membranes. We engineered various MFN-ATL chimeras to gain mechanistic insight into MFN-mediated fusion...
November 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
Dohyeong Kwon, Eunbyeol Park, Suk-Jo Kang
The stimulator of IFN genes (STING)-mediated DNA-sensing pathway plays an important role in the innate immune response to pathogen infection, autoimmunity, and cancer; however, its regulatory mechanism has not been fully elucidated, and we do not yet know whether the STING pathway is counter-regulated by other innate immune pathways. Here, we show that the NLRP3-activating agonists, ATP and nigericin, prevent STING pathway activation in association with mitochondrial fragmentation; however, the suppression of the STING pathway and mitochondria fission were not dependent on NLRP3 or potassium efflux...
November 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Ning Liu, Zhiyi Jiang, Yongjun Liu, Yao Nie, Juan Chen, Bin Ouyang, Xiangdong Guan, Minying Chen
Imbalance in mitochondrial fusion/fission is one of the mechanisms leading to sepsis‑induced mitochondrial dysfunction and cell apoptosis. The present study examined the effects of human trypsin inhibitor (UTI), a well‑known antioxidant and anti‑inflammatory substance, on mitochondrial dynamics and cell apoptosis in lipopolysaccharide (LPS)‑induced human kidney‑2 (HK‑2) cells. The HK‑2 cells were incubated for 24 h either with LPS (800 ng/ml) or LPS (800 ng/ml) mixed with UTI (250 U/ml). Cell viability was assessed using a3‑(4,5‑dimethyl‑2‑thiazolyl)‑2, 5‑diphenyl‑2‑H‑tetrazolium bromide assay...
September 2017: Molecular Medicine Reports
Jung-Yu Hsu, Yu-Ling Jhang, Pei-Hsun Cheng, Yu-Fan Chang, Su-Han Mao, Han-In Yang, Chia-Wei Lin, Chuan-Mu Chen, Shang-Hsun Yang
Spinocerebellar ataxia type 3 (SCA3), known as Machado-Joseph disease, is an autosomal dominant disease caused by an abnormal expansion of polyglutamine in ATXN3 gene, leading to neurodegeneration in SCA3 patients. Similar to other neurodegenerative diseases, the dysfunction of mitochondria is observed to cause neuronal death in SCA3 patients. Based on previous studies, proteolytic cleavage of mutant ATXN3 is found to produce truncated C-terminal fragments in SCA3 models. However, whether these truncated mutant fragments disturb mitochondrial functions and result in pathological death is still unclear...
2017: Frontiers in Molecular Neuroscience
Rogério M Borges, Alcester Mendes, Selene S C Nogueira, Jérôme Bindelle, Sérgio L G Nogueira-Filho
A nitrogen (N) balance digestion trial was conducted to determine the protein requirement of collared peccaries (Pecari tajacu). In a 4 × 4 Latin square design, four captive adult male peccaries were fed four isoenergy diets containing four different levels of N (11.7, 16.3, 22.8, and 26.7 g N/kg of dry matter-DM). After 15 days of adaptation, a total collection of feces and urine was carried out for five consecutive days. Regression analyses between N intake and N in feces and urine allowed to calculate the metabolic fecal nitrogen (MFN = 2...
October 2017: Tropical Animal Health and Production
Li Ge, Li-Hua Wei, Chang-Qing Du, Guo-Hua Song, Ya-Zhuo Xue, Hao-Shen Shi, Ming Yang, Xin-Xin Yin, Run-Ting Li, Xue-Er Wang, Zhen Wang, Wen-Gang Song
To study how hydrogen-rich saline (HS) promotes the recovery of testicular biological function in a hemi-sectioned spinal cord injury (hSCI) rat model, a right hemisection was performed at the T11-T12 of the spinal cord in Wistar rats. Animals were divided into four groups: normal group; vehicle group: sham-operated rats administered saline; hSCI group: subjected to hSCI and administered saline; HRST group: subjected to hSCI and administered HS. Hind limb neurological function, testis index, testicular morphology, mean seminiferous tubular diameter (MSTD) and seminiferous epithelial thickness (MSET), the expression of heme oxygenase-1 (HO-1), mitofusin-2 (MFN-2), and high-mobility group box 1 (HMGB-1), cell ultrastructure, and apoptosis of spermatogenic cells were studied...
June 27, 2017: Oncotarget
Katharina Gangl, Daniela M Pfabigan, Claus Lamm, Erich Kirchler, Eva Hofmann
Cooperation in social systems such as tax honesty is of central importance in our modern societies. However, we know little about cognitive and neural processes driving decisions to evade or pay taxes. This study focuses on the impact of perceived tax authority and examines the mental chronometry mirrored in ERP data allowing a deeper understanding about why humans cooperate in tax systems. We experimentally manipulated coercive and legitimate authority and studied its impact on cooperation and underlying cognitive (experiment 1, 2) and neuronal (experiment 2) processes...
July 1, 2017: Social Cognitive and Affective Neuroscience
Adam Riba, Laszlo Deres, Krisztian Eros, Aliz Szabo, Klara Magyar, Balazs Sumegi, Kalman Toth, Robert Halmosi, Eszter Szabados
In addition to their anti-bacterial action, tetracyclines also have complex biological effects, including the modification of mitochondrial protein synthesis, metabolism and gene-expression. Long-term clinical studies have been performed using tetracyclines, without significant side effects. Previous studies demonstrated that doxycycline (DOX), a major tetracyclin antibiotic, exerted a protective effect in animal models of heart failure; however, its exact molecular mechanism is still unknown. Here, we provide the first evidence that DOX reduces oxidative stress-induced mitochondrial fragmentation and depolarization in H9c2 cardiomyocytes and beneficially alters the expression of Mfn-2, OPA-1 and Drp-1 -the main regulators of mitochondrial fusion and fission-in our isoproterenol (ISO)-induced heart failure model, ultimately decreasing the severity of heart failure...
2017: PloS One
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