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Mitochondrial efficiency

Kolla Rajasekhar, Kapilkumar Mehta, Thimmaiah Govindaraju
Amyloid beta (Aβ) aggregation is the key trait responsible for the pathological devastation caused by Alzheimer's disease (AD). Among the various pathways of multifaceted toxicity exhibited by Aβ aggregates in neuronal cells, generation of reactive oxygen species (ROS) by Aβ-CuII complex and mitochondrial damage are prominent. Aβ interferes with mitochondrial transport channels, causing mitochondrial dysfunction. Herein, we present nontoxic hybrid multifunctional modulators (HMMs, TGR86-88) developed by integrating the structural and functional features of the metal chelating aggregation modulator, clioquinol (Clq) and the antioxidant epigallocatechin gallate (EGCG)...
March 20, 2018: ACS Chemical Neuroscience
Yi-Chao Hsu, Yu-Ting Wu, Chia-Ling Tsai, Yau-Huei Wei
In mammalian cells, there are seven members of the sirtuin protein family (SIRT1-7). SIRT1, SIRT6, and SIRT7 catalyze posttranslational modification of proteins in the nucleus, SIRT3, SIRT4, and SIRT5 are in the mitochondria and SIRT2 is in the cytosol. SIRT1 can deacetylate the transcription factor SOX2 and regulate induced pluripotent stem cells (iPSCs) reprogramming through the miR-34a-SIRT1-p53 axis. SIRT2 can regulate the function of pluripotent stem cells through GSK3β. SIRT3 can positively regulate PPAR gamma coactivator 1-alpha (PGC-1α) expression during the differentiation of stem cells...
March 2018: Experimental Biology and Medicine
Victoria Pons, Joan Riera, Xavier Capó, Miquel Martorell, Antoni Sureda, Josep A Tur, Franchek Drobnic, Antoni Pons
Background: Caloric restriction induces mitochondrial biogenesis and improves physical fitness in rodents. We aimed to provide evidence of how caloric restriction affects the body composition and physical performance of trained athletes and to evaluate the possible impact of an every-other-day feeding diet on nutritional deficiencies of micronutrients and essential fatty acids. Methods: The study was performed with 12 healthy male athletes by carrying out a 33% caloric restriction with respect to their usual diet...
2018: Journal of the International Society of Sports Nutrition
Noelia Morales-Prieto, Julia Ruiz-Laguna, David Sheehan, Nieves Abril
The use of DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane) in some countries, although regulated, is contributing to an increased worldwide risk of exposure to this organochlorine pesticide or its derivative p,p'-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene]. Many studies have associated p,p'-DDE exposure to type 2 diabetes, obesity and alterations of the reproductive system, but their molecular mechanisms of toxicity remain poorly understood. We have addressed this issue by using commercial microarrays based on probes for the entire Mus musculus genome to determine the hepatic transcriptional signatures of p,p'-DDE in the phylogenetically close mouse species Mus spretus...
March 16, 2018: Environmental Pollution
Lan Luo, Haibo Zhao, Qian Luo
PURPOSE: Ovarian cancer is one of the major causes of death in females around the world. There are several drug regimens available for this type of cancer, but despite initial response to chemotherapy, the disease consistently relapses, showing that there is a need to find more efficient and novel anticancer agents. Plant-derived natural products may prove beneficial in this case due to their lower cytotoxicity. In the present study we evaluated the anticancer activity of swerchirin against human SKOV3 ovarian cancer cell line...
January 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Karen Nørgaard Nielsen, Julia Peics, Tao Ma, Iuliia Karavaeva, Morten Dall, Sabina Chubanava, Astrid L Basse, Oksana Dmytriyeva, Jonas T Treebak, Zachary Gerhart-Hines
OBJECTIVE: The ability of adipose tissue to expand and contract in response to fluctuations in nutrient availability is essential for the maintenance of whole-body metabolic homeostasis. Given the nutrient scarcity that mammals faced for millions of years, programs involved in this adipose plasticity were likely evolved to be highly efficient in promoting lipid storage. Ironically, this previously advantageous feature may now represent a metabolic liability given the caloric excess of modern society...
March 7, 2018: Molecular Metabolism
Andrea K H Stavoe, Erika L F Holzbaur
Neurons are long-lived and highly polarized cells that depend on autophagy to maintain cellular homeostasis. The robust, constitutive biogenesis of autophagosomes in the distal axon occurs via a conserved pathway that is required to maintain functional synapses and prevent axon degeneration. Autophagosomes are formed de novo at the axon terminal in a stepwise assembly process, engulfing mitochondrial fragments, aggregated proteins, and bulk cytosol in what appears to be a nonselective uptake mechanism. Following formation, autophagosomes fuse with late endosomes/lysosomes and then are rapidly and efficiently transported along the axon toward the soma, driven by the microtubule motor cytoplasmic dynein...
March 13, 2018: Neuroscience Letters
Hwei-Ming Peng, Chase Barlow, Richard J Auchus
Unlike most of the drug-metabolizing cytochrome P450s, microsomal P450 17A1 and mitochondrial P450 11B2 catalyze sequential multi-step reactions in steroid biosynthesis. The membrane phospholipid composition might be one parameter that modulates the efficiency and processivity of specific pathways. Here we systematically examined the effects of physiologically relevant phospholipids on the catalysis of purified P450 17A1, P450 11B2, and P450 11B1 in reconstituted assay systems. Both dioleoylphosphatidylcholine (DOPC, 18:1) and dilauroylphosphatidylcholine (DLPC, 12:0) were found to be very efficient in reconstituting 17-hydroxylase and 17,20-lyase reactions of P450 17A1...
March 13, 2018: Journal of Steroid Biochemistry and Molecular Biology
Audrey M Bernstein, Robert Ritch, J Mario Wolosin
Exfoliation syndrome (XFS) is an age-related disease involving the deposition of aggregated fibrillar material (XFM) at extracellular matrices in tissues that synthesize elastic fibers. Its main morbidity is in the eye, where XFM accumulations form on the surface of the ciliary body, iris and lens. Exfoliation glaucoma (XFG) occurs in a high proportion of persons with XFS and can be a rapidly progressing disease. Worldwide, XFG accounts for about 25% of open-angle glaucoma cases. XFS and XFG show a sharp age-dependence, similarly to the many age-related diseases classified as aggregopathies...
March 15, 2018: Journal of Glaucoma
Haline G O Alvim, Jose Raimundo Correa, José A F Assumpção, Wender Alves da Silva, Marcelo Oliveira Rodrigues, Julio Lemos de Macedo, Mariana Fioramonte, Fabio Cesar Gozzo, Claudia C Gatto, Brenno A D Neto
The current manuscript describes the use of a heteropolyacid-containing task-specific ionic liquid, supported in imidazolium-based ionic liquids, as the catalyst for an efficient multicomponent synthesis of hexahydroimidazo[1,2-alpha]pyridine derivatives. The reactions conditions were fully optimized and the bridgehead nitrogen heterocycle derivatives could be obtained in just one hour exclusively as a single isomer (trans). Single crystal X-ray analysis confirmed the trans derivative as the only isomer. The mechanism of the reaction was investigated by ESI(+)-MS(/MS) and the use of the elegant charge-tag strategy allowed a catalytic cycle to be proposed for the current transformation and revealed the possibility of at least two reaction pathways...
March 16, 2018: Journal of Organic Chemistry
Matheus D Baldissera, Carine F Souza, Carla Cristina Zeppenfeld, Sharine Descovi, Aleksandro S da Silva, Bernardo Baldisserotto
The phosphotransfer network system, through the enzymes creatine kinase (CK), adenylate kinase (AK), and pyruvate kinase (PK), contributes to efficient intracellular energetic communication between cellular adenosine triphosphate (ATP) consumption and production in tissues with high energetic demand, such as cerebral tissue. Thus, the aim of this study was to evaluate whether aflatoxin B1 (AFB1 ) intoxication in diet negatively affects the cerebral phosphotransfer network related to impairment of cerebral ATP levels in silver catfish (Rhamdia quelen)...
March 15, 2018: Fish Physiology and Biochemistry
Takeshi Takamatsu, Marouane Baslam, Takuya Inomata, Kazusato Oikawa, Kimiko Itoh, Takayuki Ohnishi, Tetsu Kinoshita, Toshiaki Mitsui
Chloroplasts, which perform photosynthesis, are one of the most important organelles in green plants and algae. Chloroplasts maintain an independent genome that includes important genes encoding their photosynthetic machinery and various housekeeping functions. Owing to its non-recombinant nature, low mutation rates, and uniparental inheritance, the chloroplast genome (plastome) can give insights into plant evolution and ecology and in the development of biotechnological and breeding applications. However, efficient methods to obtain high-quality chloroplast DNA (cpDNA) are currently not available, impeding powerful sequencing and further functional genomics research...
2018: Frontiers in Plant Science
Adam J Chicco, Catherine H Le, Erich Gnaiger, Hans C Dreyer, Jonathan B Muyskens, Angelo D'Alessandro, Travis Nemkov, Austin D Hocker, Jessica E Prenni, Lisa M Wolfe, Nathan M Sindt, Andrew T Lovering, Andrew W Subudhi, Robert C Roach
Metabolic responses to hypoxia play important roles in cell survival strategies and disease pathogenesis in humans.  However, the homeostatic adjustments that balance changes in energy supply and demand to maintain organismal function under chronic low oxygen conditions remain incompletely understood, making it difficult to distinguish adaptive from maladaptive responses in hypoxia-related pathologies.  We integrated metabolomic and proteomic profiling with mitochondrial respirometry and blood gas analyses to comprehensively define the physiological responses of skeletal muscle energy metabolism to 16 days of high-altitude hypoxia (5260 m) in healthy volunteers from the AltitudeOmics project...
March 14, 2018: Journal of Biological Chemistry
Thomas C A Royle, Dionne Sakhrani, Camilla F Speller, Virginia L Butler, Robert H Devlin, Aubrey Cannon, Dongya Y Yang
Pacific salmonid (Oncorhynchus spp.) remains are routinely recovered from archaeological sites in northwestern North America but typically lack sexually dimorphic features, precluding the sex identification of these remains through morphological approaches. Consequently, little is known about the deep history of the sex-selective salmonid fishing strategies practiced by some of the region's Indigenous peoples. Here, we present a DNA-based method for the sex identification of archaeological Pacific salmonid remains that integrates two PCR assays that each co-amplify fragments of the sexually dimorphic on the Y chromosome (sdY) gene and an internal positive control (Clock1a or D-loop)...
2018: PloS One
Yang Yuan, Shan-Shan Pan
BACKGROUND: Late exercise preconditioning (LEP) is confirmed to have a protective effect on acute cardiovascular stress. However, the mechanisms by which mitophagy participates in EP-induced cardioprotection remain unclear. LEP may involve mitophagy mediated by the receptors PARK2 gene-encoded E3 ubiquitin ligase (Parkin) and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (Bnip3) to scavenge damaged mitochondria. METHODS: Our exercise preconditioning (EP) protocol involved four 10-minute periods of running, separated by 10-minute recovery intervals, plus a period of exhaustive running at 24 hours after EP...
March 9, 2018: Journal of Cardiovascular Pharmacology
Jingjing Zhang, Zhijun Zhang, Benshui Shu, Gaofeng Cui, Guohua Zhong
Harmine, one of the natural β-carboline alkaloids extracted from Peganum harmala L., exhibits broad spectrum but limited insecticidal ability against many pests. So there is an urgent need to synthesize novel derivatives with high efficiency. In the present study, a new synthetic compound, [1-(2-naphthyl)-3-(2-thioxo-1,3,4-oxadiazol-5-yl) β-carboline] (ZC-14), showed a strong proliferation inhibition effect against the Spodoptera frugiperda Sf9 cell line in a dose-dependent manner. Simultaneously, apoptosis induced by 7...
March 11, 2018: International Journal of Molecular Sciences
Hannah Crocker Cunningham, Kristi M Cammack, Kristin E Hales, Harvey C Freetly, Amanda K Lindholm-Perry
Feed costs account for over 70% of the annual expenditures in cow/calf production. During the production year the cow uses nutrients to support conceptus growth, milk production, work (grazing and locomotion), and maintenance requirements. The majority of the nutrients are used to support maintenance. Substrate cycling has been identified as one of the major contributors toward energy expenditure associated with maintenance in mature cows. The objective of this study was to determine whether beef cows that differ in the efficiency of weight gain differ in the relative abundance of transcripts for metabolic regulation in adipose tissue...
2018: PloS One
Javier Gandasegui, Pedro Fernández-Soto, Antonio Muro, Constança Simões Barbosa, Fabio Lopes de Melo, Rodrigo Loyo, Elainne Christine de Souza Gomes
BACKGROUND: In Brazil, schistosomiasis is a parasitic disease of public health relevance, mainly in poor areas where Schistosoma mansoni is the only human species encountered and Biomphalaria straminea is one of the intermediate host snails. A nested-PCR based on a specific mitochondrial S. mansoni minisatellite DNA region has been successfully developed and applied as a reference method in Brazil for S. mansoni detection, mainly in host snails for epidemiological studies. The amplification efficiency of LAMP is known to be higher than PCR...
March 2018: PLoS Neglected Tropical Diseases
Jacob D Aguirre, Karen M Dunkerley, Rica Lam, Michele Rusal, Gary S Shaw
Autosomal recessive juvenile Parkinsonism (ARJP) is an inherited neurodegenerative disease in which 50% of affected individuals harbor mutations in the gene encoding the E3 ligase parkin. Parkin regulates the mitochondrial recycling pathway, which is induced by oxidative stress. In its native state, parkin is autoinhibited by its N-terminal ubiquitin-like (Ubl) domain which blocks the binding site for an incoming E2~ubiquitin conjugate, needed for parkin's ubiquitination activity. Parkin is activated via phosphorylation of Ser65 in its Ubl domain by PTEN-induced putative kinase 1 (PINK1) and an ubiquitin molecule phosphorylated at a position equivalent to Ser65 in parkin...
March 12, 2018: Journal of Biological Chemistry
Erzsebet Polyak, Julian Ostrovsky, Min Peng, Stephen D Dingley, Mai Tsukikawa, Young Joon Kwon, Shana E McCormack, Michael Bennett, Rui Xiao, Christoph Seiler, Zhe Zhang, Marni J Falk
Oxidative stress is a known contributing factor in mitochondrial respiratory chain (RC) disease pathogenesis. Yet, no efficient means exists to objectively evaluate the comparative therapeutic efficacy or toxicity of different antioxidant compounds empirically used in human RC disease. We postulated that pre-clinical comparative analysis of diverse antioxidant drugs having suggested utility in primary RC disease using animal and cellular models of RC dysfunction may improve understanding of their integrated effects and physiologic mechanisms, and enable prioritization of lead antioxidant molecules to pursue in human clinical trials...
February 23, 2018: Molecular Genetics and Metabolism
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