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Mitochondrial pharmacology

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https://www.readbyqxmd.com/read/28091829/inhibition-of-dpp-4-activity-and-neuronal-atrophy-with-genistein-attenuates-neurological-deficits-induced-by-transient-global-cerebral-ischemia-and-reperfusion-in-streptozotocin-induced-diabetic-mice
#1
Mithun Singh Rajput, Purnima Dey Sarkar, Nilesh Prakash Nirmal
Genistein, an isoflavonoid phytoestrogen, has been known for its potential pharmacological properties especially for neuroprotection and treating diabetes. The present study aims to determine the neuroprotective efficacy of genistein against global cerebral ischemia-reperfusion-induced neuronal injury in streptozotocin-induced diabetic mice and explore the underlying mechanisms. Streptozotocin-induced diabetic mice were subjected to transient cerebral ischemia by occluding both common carotid arteries for 30 min followed by 24 h reperfusion to induce neuronal injury...
January 16, 2017: Inflammation
https://www.readbyqxmd.com/read/28088331/eicosapentaenoic-acid-ameliorates-palmitate-induced-lipotoxicity-via-the-amp-kinase-dynamin-related-protein-1-signaling-pathway-in-differentiated-h9c2-myocytes
#2
Atsushi Sakamoto, Masao Saotome, Prottoy Hasan, Terumori Satoh, Hayato Ohtani, Tsuyoshi Urushida, Hideki Katoh, Hiroshi Satoh, Hideharu Hayashi
BACKGROUND: Emerging evidence suggested the preferable effects of eicosapentaenoic acid (EPA; n-3 polyunsaturated fatty acid) against cardiac lipotoxicity, which worsens cardiac function by means of excessive serum free fatty acids due to chronic adrenergic stimulation under heart failure. Nonetheless, the precise molecular mechanisms remain elusive. In this study, we focused on dynamin-related protein-1 (Drp1) as a possible modulator of the EPA-mediated cardiac protection against cardiac lipotoxicity, and investigated the causal relation between AMP-activated protein kinase (AMPK) and Drp1...
January 11, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28078981/resilience-to-alzheimer-s-disease-the-role-of-physical-activity
#3
Pedrinolla Anna, Schena Federico, Venturelli Massimo
BACKGROUND: Although Alzheimer's disease (AD) is a neurodegenerative pathology characterized by accumulation of β-amyloid plaques and neurofibrillary tangles at cerebral level, recent studies highlighted that AD might be the result of many altered physiological processes occurring at whole-organism level. The ability to adapt to stressors by "bending" but not "breaking" can be considered as "resilience". Individuals incline to withstand such pathophysiological challenges, can be considered more resilient than those that do not...
January 11, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28077358/biological-signaling-by-carbon-monoxide-and-carbon-monoxide-releasing-molecules-co-rms
#4
Roberto Motterlini, Roberta Foresti
Carbon monoxide (CO) is continuously produced in mammalian cells during degradation of heme. It is a stable gaseous molecule that reacts selectively with transition metals in a specific redox state and these characteristics restrict the interaction of CO with defined biological targets that transduce its signaling activity. Because of the high affinity of CO for ferrous heme, these targets can be grouped into heme-containing proteins, representing a large variety of sensors and enzymes with a series of diverse function in the cell and the organism...
January 11, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28069926/creatine-enhances-mitochondrial-mediated-oligodendrocyte-survival-following-demyelinating-injury
#5
Kelly A Chamberlain, Kristen S Chapey, Sonia E Nanescu, Jeffrey K Huang
: Chronic oligodendrocyte loss, which occurs in the demyelinating disorder multiple sclerosis (MS), contributes to axonal dysfunction and neurodegeneration. Current therapies are able to reduce MS severity, but do not prevent transition into the progressive phase of the disease, which is characterized by chronic neurodegeneration. Therefore, pharmacological compounds that promote oligodendrocyte survival could be beneficial for neuroprotection in MS. Here, we investigated the role of creatine, an organic acid involved in ATP buffering, in oligodendrocyte function...
January 9, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28069354/bufadienolides-from-amphibians-a-promising-source-of-anticancer-prototypes-for-radical-innovation-apoptosis-triggering-and-na-k-atpase-inhibition
#6
REVIEW
Lívia Queiroz de Sousa, Kátia da Conceição Machado, Samara Ferreira de Carvalho Oliveira, Lidiane da Silva Araújo, Evaldo Dos Santos Monção-Filho, Ana Amélia de Carvalho Melo-Cavalcante, Gerardo Magela Vieira-Júnior, Paulo Michel Pinheiro Ferreira
Amphibians present pharmacologically active aliphatic, aromatic and heterocyclic molecules in their skin as defense against microorganisms, predators and infections, such as steroids, alkaloids, biogenic amines, guanidine derivatives, proteins and peptides. Based on the discovered bioactive potential of bufadienolides, this work reviewed the contribution of amphibians, especially from members of Bufonidae family, as source of new cytotoxic and antitumor molecules, highlighting the mechanisms responsible for such amazing biological potentialities...
January 6, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28067471/traditional-and-novel-tools-to-probe-the-mitochondrial-metabolism-in-health-and-disease
#7
REVIEW
Yanfei Zhang, José L Avalos
Mitochondrial metabolism links energy production to other essential cellular processes such as signaling, cellular differentiation, and apoptosis. In addition to producing adenosine triphosphate (ATP) as an energy source, mitochondria are responsible for the synthesis of a myriad of important metabolites and cofactors such as tetrahydrofolate, α-ketoacids, steroids, aminolevulinic acid, biotin, lipoic acid, acetyl-CoA, iron-sulfur clusters, heme, and ubiquinone. Furthermore, mitochondria and their metabolism have been implicated in aging and several human diseases, including inherited mitochondrial disorders, cardiac dysfunction, heart failure, neurodegenerative diseases, diabetes, and cancer...
January 9, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/28063595/the-mitochondrial-targeted-peptide-ss-31-improves-glomerular-architecture-in-mice-of-advanced-age
#8
Mariya T Sweetwyne, Jeffrey W Pippin, Diana G Eng, Kelly L Hudkins, Ying Ann Chiao, Matthew D Campbell, David J Marcinek, Charles E Alpers, Hazel H Szeto, Peter S Rabinovitch, Stuart J Shankland
Although age-associated changes in kidney glomerular architecture have been described in mice and man, the mechanisms are unknown. It is unclear if these changes can be prevented or even reversed by systemic therapies administered at advanced age. Using light microscopy and transmission electron microscopy, our results showed glomerulosclerosis with injury to mitochondria in glomerular epithelial cells in mice aged 26 months (equivalent to a 79-year-old human). To test the hypothesis that reducing mitochondrial damage in late age would result in lowered glomerulosclerosis, we administered the mitochondrial targeted peptide, SS-31, to aged mice...
January 4, 2017: Kidney International
https://www.readbyqxmd.com/read/28063379/oxidative-stress-mitochondrial-abnormalities-and-antioxidant-defense-in-ataxia-telangiectasia-bloom-syndrome-and-nijmegen-breakage-syndrome
#9
REVIEW
Mateusz Maciejczyk, Bozena Mikoluc, Barbara Pietrucha, Edyta Heropolitanska-Pliszka, Malgorzata Pac, Radosław Motkowski, Halina Car
Rare pleiotropic genetic disorders, Ataxia-telangiectasia (A-T), Bloom syndrome (BS) and Nijmegen breakage syndrome (NBS) are characterised by immunodeficiency, extreme radiosensitivity, higher cancer susceptibility, premature aging, neurodegeneration and insulin resistance. Some of these functional abnormalities can be explained by aberrant DNA damage response and chromosomal instability. It has been suggested that one possible common denominator of these conditions could be chronic oxidative stress caused by endogenous ROS overproduction and impairment of mitochondrial homeostasis...
December 28, 2016: Redox Biology
https://www.readbyqxmd.com/read/28061969/role-of-nitric-oxide-in-stress-induced-anxiety-from-pathophysiology-to-therapeutic-target
#10
A Kumar, P Chanana
Stress is often marked by a state of hyperarousal to aid the initiation of necessary stress response for the successful management of stressful stimuli. It can be manifested as a challenge (stimulus) that requires behavioral, psychological, and physiological adaptations for the maintenance of a state of homeostasis in response to stressful stimuli. In an organism, miscellaneous stressors trigger a wide spectrum of alterations in hormonal and neuronal physiologies, resulting in behavioral (anxiety and depression disorders, diminished food intake and gastrointestinal dysfunctions, decline in sexual behavior, diabetes, and loss of cognitive function) and other physiological responses...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28055012/aif-independent-parthanatos-in-the-pathogenesis-of-dry-age-related-macular-degeneration
#11
Ki-Hong Jang, Yun-Ju Do, Dongwon Son, Eunji Son, Jun-Sub Choi, Eunhee Kim
Cell death of retinal pigment epithelium (RPE) is characterized as an essential late-stage phenomenon of dry age-related macular degeneration (AMD). The aim of this study was to elucidate the molecular mechanism underlying RPE cell death after exposure to oxidative stress, which occurs often because of the anatomical location of RPE cells. ARPE-19, an established RPE cell line, exhibited necrotic features involving poly (ADP-ribose) polymerase-1 (PARP-1) activation in response to hydrogen peroxide (H2O2). ARPE-19 cells were resistant to H2O2 when PARP-1 was depleted using siRNA or inhibited by a pharmacological inhibitor of PARP-1, olaparib...
January 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28053881/effect-of-novel-dietary-supplement-on-metabolism-in%C3%A2-vitro-and-in%C3%A2-vivo
#12
Roger A Vaughan, Ailish C White, Jason R Beam, Nicholas P Gannon, Randi Garcia-Smith, Roy M Salgado, Marco Bisoffi, Kristina A Trujillo, Carole A Conn, Christine M Mermier
Obesity is an increasingly prevalent and preventable morbidity with multiple behavioral, surgical and pharmacological interventions currently available. Commercial dietary supplements are often advertised to stimulate metabolism and cause rapid weight and/or fat loss, although few well-controlled studies have demonstrated such effects. We describe a commercially available dietary supplement (purportedly containing caffeine, catechins, and other metabolic stimulators) on resting metabolic rate in humans, and on metabolism, mitochondrial content, and related gene expression in vitro...
January 2017: Journal of Traditional and Complementary Medicine
https://www.readbyqxmd.com/read/28050232/identification-of-cetp-as-a-molecular-target-for-estrogen-positive-breast-cancer-cell-death-by-cholesterol-depleting-agents
#13
Luke Esau, Sunil Sagar, Dhinoth Bangarusamy, Mandeep Kaur
Cholesterol and its metabolites act as steroid hormone precursors, which promote estrogen receptor positive (ER+) breast cancer (BC) progression. Development of cholesterol targeting anticancer drugs has been hindered due to the lack of knowledge of viable molecular targets. Till now, Cholesteryl ester transfer protein (CETP) has been envisaged as a feasible molecular target in atherosclerosis, but for the first time, we show that CETP contributes to BC cell survival when challenged with cholesterol depleting agents...
September 2016: Genes & Cancer
https://www.readbyqxmd.com/read/28049732/nadph-oxidase-4-nox4-suppresses-mitochondrial-biogenesis-and-bioenergetics-in-lung-fibroblasts-via-a-nuclear-factor-erythroid-derived-2-like-2-nrf2-dependent-pathway
#14
Karen Bernard, Naomi J Logsdon, Veronica Miguel, Gloria A Benavides, Jianhua Zhang, A Brent Carter, Victor M Darley-Usmar, Victor J Thannickal
Mitochondrial bioenergetics are critical for cellular homeostasis and stress responses. The reactive oxygen species (ROS)-generating enzyme, NADPH oxidase 4 (Nox4), regulates a number of physiological and pathological processes, including cellular differentiation, host defense and tissue fibrosis. In this study, we explored the role of constitutive Nox4 activity in regulating mitochondrial function. An increase in mitochondrial oxygen consumption and reserve capacity was observed in murine and human lung fibroblasts with genetic deficiency (or silencing) of Nox4...
January 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28045936/detoxification-of-mitochondrial-oxidants-and-apoptotic-signaling-are-facilitated-by-thioredoxin-2-and-peroxiredoxin-3-during-hyperoxic-injury
#15
Benjamin J Forred, Darwin R Daugaard, Brianna K Titus, Ryan R Wood, Miranda J Floen, Michelle L Booze, Peter F Vitiello
Mitochondria play a fundamental role in the regulation of cell death during accumulation of oxidants. High concentrations of atmospheric oxygen (hyperoxia), used clinically to treat tissue hypoxia in premature newborns, is known to elicit oxidative stress and mitochondrial injury to pulmonary epithelial cells. A consequence of oxidative stress in mitochondria is the accumulation of peroxides which are detoxified by the dedicated mitochondrial thioredoxin system. This system is comprised of the oxidoreductase activities of peroxiredoxin-3 (Prx3), thioredoxin-2 (Trx2), and thioredoxin reductase-2 (TrxR2)...
2017: PloS One
https://www.readbyqxmd.com/read/28045016/the-three-herb-formula-shuang-huang-lian-stabilizes-mast-cells-through-activation-of-mitochondrial-calcium-uniporter
#16
Yuan Gao, Rui Hou, Qiaoling Fei, Lei Fang, Yixin Han, Runlan Cai, Cheng Peng, Yun Qi
Mast cells (MCs) are key effector cells of IgE-FcεRI- or MrgprX2-mediated signaling event. Shuang-Huang-Lian (SHL), a herbal formula from Chinese Pharmacopoeia, has been clinically used in type I hypersensitivity. Our previous study demonstrated that SHL exerted a non-negligible effect on MC stabilization. Herein, we sought to elucidate the molecular mechanisms of the prominent anti-allergic ability of SHL. MrgprX2- and IgE-FcεRI-mediated MC activation in vitro and in vivo models were developed by using compound 48/80 (C48/80) and shrimp tropomyosin (ST), respectively...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28039397/physical-exercise-in-aging-human-skeletal-muscle-increases-mitochondrial-calcium-uniporter-expression-levels-and-affects-mitochondria-dynamics
#17
Sandra Zampieri, Cristina Mammucari, Vanina Romanello, Laura Barberi, Laura Pietrangelo, Aurora Fusella, Simone Mosole, Gaia Gherardi, Christian Höfer, Stefan Löfler, Nejc Sarabon, Jan Cvecka, Matthias Krenn, Ugo Carraro, Helmut Kern, Feliciano Protasi, Antonio Musarò, Marco Sandri, Rosario Rizzuto
Age-related sarcopenia is characterized by a progressive loss of muscle mass with decline in specific force, having dramatic consequences on mobility and quality of life in seniors. The etiology of sarcopenia is multifactorial and underlying mechanisms are currently not fully elucidated. Physical exercise is known to have beneficial effects on muscle trophism and force production. Alterations of mitochondrial Ca(2+) homeostasis regulated by mitochondrial calcium uniporter (MCU) have been recently shown to affect muscle trophism in vivo in mice...
December 2016: Physiological Reports
https://www.readbyqxmd.com/read/28034771/lkb1-promotes-metabolic-flexibility-in-response-to-energy-stress
#18
Seth J Parker, Robert U Svensson, Ajit S Divakaruni, Austin E Lefebvre, Anne N Murphy, Reuben J Shaw, Christian M Metallo
The Liver Kinase B1 (LKB1) tumor suppressor acts as a metabolic energy sensor to regulate AMP-activated protein kinase (AMPK) signaling and is commonly mutated in various cancers, including non-small cell lung cancer (NSCLC). Tumor cells deficient in LKB1 may be uniquely sensitized to metabolic stresses, which may offer a therapeutic window in oncology. To address this question we have explored how functional LKB1 impacts the metabolism of NSCLC cells using (13)C metabolic flux analysis. Isogenic NSCLC cells expressing functional LKB1 exhibited higher flux through oxidative mitochondrial pathways compared to those deficient in LKB1...
December 26, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/28034647/synthesis-and-biological-evaluation-of-cis-restricted-triazole-tetrazole-mimics-of-combretastatin-benzothiazole-hybrids-as-tubulin-polymerization-inhibitors-and-apoptosis-inducers
#19
A V Subba Rao, Konderu Swapna, Siddiq Pasha Shaik, V Lakshma Nayak, T Srinivasa Reddy, Satish Sunkari, Thokhir Basha Shaik, Chandrakant Bagul, Ahmed Kamal
A series of colchicine site binding tubulin inhibitors were synthesized by the modification of the combretastatin pharmacophore. The ring B was replaced by the pharmacologically relevant benzothiazole scaffolds, and the cis configuration of the olefinic bond was restricted by the incorporation of a triazole and tetrazole rings which is envisaged by the structural resemblance to a tubulin inhibitor like combretastatin (CA-4). These compounds were evaluated for their antiproliferative activity on selected cancer cell lines and an insight in the structure activity relationship was developed...
December 9, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28034298/effective-agents-targeting-the-mitochondria-and-apoptosis-to-protect-the-heart
#20
Eltyeb Abdelwahid, Aurimas Stulpinas, Audrone Kalvelyte
A wide variety of agents have been traditionally used in cardiovascular medicine worldwide and their precise mechanisms of action have been demonstrated to be largely related to the cardiomyocyte mitochondria and apoptosis. Abnormalities in the structure and function of the mitochondria and mutations in mitochondrial DNA can decrease energy production, alter the redox system, impair calcium homeostasis, and induce the mitochondrial permeability transition pore (MPTP), causing cell death. All of these data provide evidence of mitochondrial signaling pathways as targets to downregulate cardiac cell apoptosis and thus to prevent and treat cardiovascular diseases...
December 29, 2016: Current Pharmaceutical Design
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