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Mitochondrial pharmacology

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https://www.readbyqxmd.com/read/28214329/-p-clphse-2-reduces-hepatotoxicity-induced-by-monosodium-glutamate-by-improving-mitochondrial-function-in-rats
#1
Caroline B Quines, Pietro M Chagas, Diane Hartmann, Nélson R Carvalho, Félix A Soares, Cristina W Nogueira
It is has been demonstrated that mitochondrial dysfunction, oxidative stress and chronic inflammatory process are associated with progress of morbid obesity in human patients. For this reason, the searching for safe and effective antiobesity drugs has been the subject of intense research. In this context, the organic selenium compounds have attracted much attention due to their pharmacological properties, such as antihyperglycemic, antioxidant and anti-inflammatory. The aim of this study was to evaluate the hepatoprotective action of p-chloro-diphenyl diselenide (p-ClPhSe)2 , an organic selenium compound, in a model of obesity induced by monosodium glutamate (MSG) administration in rats...
February 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28210207/cannabinoid-receptor-2-signaling-in-neurodegenerative-disorders-from-pathogenesis-to-a-promising-therapeutic-target
#2
REVIEW
Tommaso Cassano, Silvio Calcagnini, Lorenzo Pace, Federico De Marco, Adele Romano, Silvana Gaetani
As a consequence of an increasingly aging population, the number of people affected by neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, is rapidly increasing. Although the etiology of these diseases has not been completely defined, common molecular mechanisms including neuroinflammation, excitotoxicity and mitochondrial dysfunction have been confirmed and can be targeted therapeutically. Moreover, recent studies have shown that endogenous cannabinoid signaling plays a number of modulatory roles throughout the central nervous system (CNS), including the neuroinflammation and neurogenesis...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28207742/narciclasine-attenuates-diet-induced-obesity-by-promoting-oxidative-metabolism-in-skeletal-muscle
#3
Sofi G Julien, Sun-Yee Kim, Reinhard Brunmeir, Joanna R Sinnakannu, Xiaojia Ge, Hongyu Li, Wei Ma, Jadegoud Yaligar, Bhanu Prakash Kn, Sendhil S Velan, Pia V Röder, Qiongyi Zhang, Choon Kiat Sim, Jingyi Wu, Marta Garcia-Miralles, Mahmoud A Pouladi, Wei Xie, Craig McFarlane, Weiping Han, Feng Xu
Obesity develops when caloric intake exceeds metabolic needs. Promoting energy expenditure represents an attractive approach in the prevention of this fast-spreading epidemic. Here, we report a novel pharmacological strategy in which a natural compound, narciclasine (ncls), attenuates diet-induced obesity (DIO) in mice by promoting energy expenditure. Moreover, ncls promotes fat clearance from peripheral metabolic tissues, improves blood metabolic parameters in DIO mice, and protects these mice from the loss of voluntary physical activity...
February 2017: PLoS Biology
https://www.readbyqxmd.com/read/28206988/inhibition-of-autophagy-blocks-cathepsins-tbid-mitochondrial-apoptotic-signaling-pathway-via-stabilization-of-lysosomal-membrane-in-ischemic-astrocytes
#4
Xian-Yong Zhou, Yu Luo, Yong-Ming Zhu, Zhi-He Liu, Thomas A Kent, Jia-Guo Rong, Wei Li, Shi-Gang Qiao, Min Li, Yong Ni, Kazumi Ishidoh, Hui-Ling Zhang
Our previous study and others have demonstrated that autophagy is activated in ischemic astrocytes and contributes to astrocytic cell death. However, the mechanisms of ischemia-induced autophagy remain largely unknown. In this study, we established a rat's model of permanent middle cerebral artery occlusion (pMCAO) and an in vitro oxygen and glucose deprivation (OGD) model. Autophagy was inhibited by either pharmacological treatment with 3-methyladenine (3-MA) and wortmannin (Wort) or genetic treatment with knockdown of Atg5 in primary cultured astrocytes and knockout of Atg5 in mouse embryonic fibroblast (MEF) cells, respectively...
February 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28205173/measurement-of-mitochondrial-cholesterol-import-using-a-mitochondria-targeted-cyp11a1-fusion-construct
#5
Barry E Kennedy, Mark Charman, Barbara Karten
All animal membranes require cholesterol as an essential regulator of biophysical properties and function, but the levels of cholesterol vary widely among different subcellular compartments. Mitochondria, and in particular the inner mitochondrial membrane, have the lowest levels of cholesterol in the cell. Nevertheless, mitochondria need cholesterol for membrane maintenance and biogenesis, as well as oxysterol, steroid, and hepatic bile acid production. Alterations in mitochondrial cholesterol have been associated with a range of pathological conditions, including cancer, hepatosteatosis, cardiac ischemia, Alzheimer's, and Niemann-Pick Type C Disease...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28199134/genetic-control-of-fatty-acid-%C3%AE-oxidation-in-chronic-obstructive-pulmonary-disease
#6
Zhiqiang Jiang, Nelson H Knudsen, Gang Wang, Weiliang Qiu, Zun Zar Chi Naing, Yan Bai, Xingbin Ai, Chih-Hao Lee, Xiaobo Zhou
Bioenergetics homeostasis is important for cells to sustain normal functions and defend against injury. Genetics controls on bioenergetics homeostasis, especially lipid metabolism remain poorly understood in chronic obstructive pulmonary diseases (COPD), the third leading cause of death in the world. Additionally, biological function of most susceptible genes identified from genome-wide association studies (GWAS) in COPD remains unclear. Here, we aim to address 1) how fatty acid oxidation, specifically β-oxidation (FAO), a key lipid metabolism pathway that provides energy to cells, contributes to cigarette smoke (CS)-induced COPD; and 2) whether and how FAM13A (family with sequence similarity 13 member A), a well-replicated COPD GWAS gene, modulates FAO pathway...
February 15, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28194521/the-mitochondrial-ca-2-uniporter-structure-function-and-pharmacology
#7
Jyotsna Mishra, Bong Sook Jhun, Stephen Hurst, Jin O-Uchi, György Csordás, Shey-Shing Sheu
Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex.
February 14, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28194038/itd-mutation-in-flt3-tyrosine-kinase-promotes-warburg-effect-and-renders-therapeutic-sensitivity-to-glycolytic-inhibition
#8
H-Q Ju, G Zhan, A Huang, Y Sun, S Wen, J Yang, W-H Lu, R-H Xu, J Li, Y Li, G Garcia-Manero, P Huang, Y Hu
Internal tandem duplication (ITD) mutation in Fms-like tyrosine kinase 3 gene (FLT3/ITD) represents an unfavorable genetic change in acute myeloid leukemia (AML) and is associated with poor prognosis. Metabolic alterations have been involved in tumor progression and attracted interest as a target for therapeutic intervention. However, few studies analyzed the adaptations of cellular metabolism in the context of FLT3/ITD mutation. Here, we report that FLT3/ITD causes a significant increase in aerobic glycolysis through AKT-mediated upregulation of mitochondrial hexokinase (HK2), and renders the leukemia cells highly dependent on glycolysis and sensitive to pharmacological inhibition of glycolytic activity...
February 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28192990/dual-stimuli-activatable-oxidative-stress-amplifying-agent-as-a-hybrid-anticancer-prodrug
#9
Eunji Han, Byeongsu Kwon, Donghyuck Yoo, Changsun Kang, Gilson Khang, Dongwon Lee
Compared to normal cells, cancer cells have a higher level of reactive oxygen species (ROS) due to aberrant metabolism and disruption of redox homeostasis which drive their proliferation and promote progression and metastasis of cancers. The altered redox balance and biological difference between normal cells and cancer cells provide a basis for the development of anticancer agents which are able to generate pharmacological ROS insults to kill cancer cells preferentially. In this study, we report a new hybrid anticancer drug, termed OSamp, which undergoes esterase- and acid-catalyzed hydrolysis to deplete antioxidant glutathione (GSH) and generate ROS, simultaneously...
February 13, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28192232/real-time-quantification-of-subcellular-h202-and-glutathione-redox-potential-in-living-cardiovascular-tissues
#10
Emiliano Panieri, Carlo Millia, Massimo M Santoro
Detecting and measuring the dynamic redox events that occur in vivo is a prerequisite for understanding the impact of oxidants and redox events in normal and pathological conditions. These aspects are particularly relevant in cardiovascular tissues wherein alterations of the redox balance are associated with stroke, aging, and pharmacological intervention. An ambiguous aspect of redox biology is how redox events occur in subcellular organelles including mitochondria, and nuclei. Genetically-encoded Rogfp2 fluorescent probes have become powerful tools for real-time detection of redox events...
February 10, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28190473/eucalrobusone-c-suppresses-cell-proliferation-and-induces-ros-dependent-mitochondrial-apoptosis-via-the-p38-mapk-pathway-in-hepatocellular-carcinoma-cells
#11
Kai-Li Jian, Chao Zhang, Zhi-Chun Shang, Lei Yang, Ling-Yi Kong
BACKGROUND: Eucalyptus extracts have anti-cancer activity against various cancer cells. Formyl-phloroglucinol meroterpenoids (FPMs), which are typical secondary metabolites of the genera Eucalyptus, have many important pharmacological activities. PURPOSE: Eucalrobusone C (EC), a new bioactive phytochemical, was first isolated from the leaves of Eucalyptus robusta in our laboratory. EC is a FPM, and our previous research revealed that EC showed strongest cytotoxicity in three cancer models than other compounds isolated from the leaves of E...
February 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28181523/mitochondria-play-an-important-role-in-the-cell-proliferation-suppressing-activity-of-berberine
#12
Xiao-Jin Yan, Xuan Yu, Xin-Pei Wang, Jing-Fei Jiang, Zhi-Yi Yuan, Xi Lu, Fan Lei, Dong-Ming Xing
After being studied for approximately a century, berberine (BBR) has been found to act on various targets and pathways. A great challenge in the pharmacological analysis of BBR at present is to identify which target(s) plays a decisive role. In the study described herein, a rescue experiment was designed to show the important role of mitochondria in BBR activity. A toxic dose of BBR was applied to inhibit cell proliferation and mitochondrial activity, then α-ketobutyrate (AKB), an analogue of pyruvate that serves only as an electron receptor of NADH, was proven to partially restore cell proliferation...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28181078/puerarin-may-protect-against-schwann-cell-damage-induced-by-glucose-fluctuation
#13
Bing Xue, Lin Wang, Zhe Zhang, Rui Wang, Xin-Xin Xia, Ping-Ping Han, Li-Jun Cao, Yong-Hui Liu, Lian-Qing Sun
Puerarin is one of the major active ingredients in Gegen, a traditional Chinese herb that has been reported to have a wide variety of beneficial pharmacology functions. Previous studies have implicated that the damaging effects of hyperglycemia resulting from oxidative stress and glucose fluctuation may be more dangerous than constant high glucose in the development of diabetes-related complications. The present study focuses on the effects of puerarin on glucose fluctuation-induced oxidative stress-induced Schwann cell (SC) apoptosis in vitro...
February 8, 2017: Journal of Natural Medicines
https://www.readbyqxmd.com/read/28178613/lasalocid-induces-cytotoxic-apoptosis-and-cytoprotective-autophagy-through-reactive-oxygen-species-in-human-prostate-cancer-pc-3-cells
#14
Kwang-Youn Kim, Sang-Hun Kim, Sun-Nyoung Yu, Sul-Gi Park, Young-Wook Kim, Hyo-Won Nam, Hyun-Hee An, Hak-Sun Yu, Young Woo Kim, Jae-Hoon Ji, Young-Kyo Seo, Soon-Cheol Ahn
Lasalocid is an antibiotic from the group of carboxylic ionophores, produced by Streptomyces lasaliensis. But there was limited information of lasalocid on human prostate cancer cells. In the present studies, to better understand its effect in human prostate cancer cells, apoptosis and autophagy associated with possible signal pathways in vitro was examined. Our study showed that lasalocid mediated cell cycle arrest in G0/G1 phase by reducing G1 phase dependent proteins, indicating entering into apoptotic cell death pathway...
February 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28177892/pevonedistat-a-nedd8-activating-enzyme-inhibitor-sensitizes-neoplastic-b-cells-to-death-receptor-mediated-apoptosis
#15
Cody Paiva, J Claire Godbersen, Taylor Rowland, Olga V Danilova, Christopher Danes, Allison Berger, Alexey V Danilov
While death receptor ligands (Fas and TRAIL) kill chemoresistant tumor cell lines, related therapies have limited clinical efficacy as single agents. Death receptor signaling is modulated by nuclear factor-κB (NFκB), a family of transcription factors which are constitutively active in B-cell malignancies. We and others have shown that pevonedistat, an investigational inhibitor of the NEDD8-activating enzyme, abrogates NFκB activity in B-cell neoplasia. Here we demonstrate that diffuse large B-cell lymphoma, particularly activated B-cell type, and primary chronic lymphocytic leukemia cells are re-sensitized to extrinsic apoptosis by pevonedistat...
February 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28177676/protective-effects-and-plausible-mechanisms-of-velvet-polypeptide-against-hydrogen-peroxide-induced-injury-in-human-umbilical-vein-endothelial-cells
#16
Wenhe Zhu, Huiyan Wang, Wei Zhang, Na Xu, Junjie Xu, Yan Li, Wensen Liu, Shijie Lv
Velvet antler polypeptide (VAP) is a prominent bioactive component of velvet antlers. Whereas, uncharacterized crude extracts were usually employed in pharmacological studies. In this study, the velvet polypeptide was isolated and purified by acid water extraction, ethanol precipitation, and ammonium sulfate fractionation and precipitation, and chromatography progressively. Human umbilical vein endothelial cells (HUVECs) were induced by H2O2 followed purified polypeptide treatment. Cell viability was evaluated by MTT assay...
January 4, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28174522/in-vivo-imaging-of-mitochondrial-transport-in-single-axon-regeneration-of-zebrafish-mauthner-cells
#17
Yang Xu, Min Chen, Bingbing Hu, Rongchen Huang, Bing Hu
Mitochondrial transport is essential for neuronal function, but the evidence of connections between mitochondrial transport and axon regeneration in the central nervous system (CNS) of living vertebrates remains limited. Here, we developed a novel model to explore mitochondrial transport in a single Mauthner axon (M axon) of zebrafish with non-invasive in vivo imaging. To confirm the feasibility of using this model, we treated labeled zebrafish with nocodazole and demonstrated that it could disrupt mitochondrial transport...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28174288/direct-substrate-delivery-into-mitochondrial-fission-deficient-pancreatic-islets-rescues-insulin-secretion
#18
Uma D Kabra, Katrin Pfuhlmann, Adriana Migliorini, Susanne Keipert, Daniel Lamp, Olle Korsgren, Moritz Gegg, Stephen C Woods, Paul T Pfluger, Heiko Lickert, Charles Affourtit, Matthias H Tschöp, Martin Jastroch
In pancreatic beta cells, mitochondrial bioenergetics control glucose-stimulated insulin secretion (GSIS). Mitochondrial dynamics are generally associated with quality control, maintaining the functionality of bioenergetics. By acute pharmacological inhibition of mitochondrial fission protein Drp1, we here demonstrate that mitochondrial fission is necessary for GSIS in mouse and human islets. We confirm that genetic silencing of Drp1 increases mitochondrial proton leak in MIN6 cells. However, our comprehensive analysis of pancreatic islet bioenergetics reveals that Drp1 does not control insulin secretion via its effect on proton leak but instead via modulation of glucose-fuelled respiration...
February 7, 2017: Diabetes
https://www.readbyqxmd.com/read/28173848/inhibition-of-dynamin-related-protein-1-protects-against-myocardial-ischemia-reperfusion-injury-in-diabetic-mice
#19
Mingge Ding, Qianqian Dong, Zhenghua Liu, Zheng Liu, Yinxian Qu, Xing Li, Cong Huo, Xin Jia, Feng Fu, Xiaoming Wang
BACKGROUND: Many cardioprotective pharmacological agents failed to exert their protective effects in diabetic hearts subjected to myocardial ischemia/reperfusion (MI/R). Identify the molecular basis linking diabetes with MI/R injury is scientifically important and may provide effective therapeutic approaches. Dynamin-related protein 1 (Drp1)-mediated mitochondrial fission plays an important role in MI/R injury under non-diabetic conditions. Importantly, recent studies indicated that Drp1-mediated mitochondrial fission is enhanced in the myocardium of diabetic mice...
February 7, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28173640/tanshinone-iia-protects-endothelial-cells-from-h2o2-induced-injuries-via-pxr-activation
#20
Haiyan Zhu, Zhiwu Chen, Zengchun Ma, Hongling Tan, Chengrong Xiao, Xianglin Tang, Boli Zhang, Yuguang Wang, Yue Gao
Tanshinone IIA (Tan IIA) is a pharmacologically active substance extracted from the rhizome of Salvia miltiorrhiza Bunge (also known as the Chinese herb Danshen), and is widely used to treat atherosclerosis. The pregnane X receptor (PXR) is a nuclear receptor that is a key regulator of xenobiotic and endobiotic detoxification. Tan IIA is an efficacious PXR agonist that has a potential protective effect on endothelial injuries induced by xenobiotics and endobiotics via PXR activation. Previously numerous studies have demonstrated the possible effects of Tan IIA on human umbilical vein endothelial cells, but the further mechanism for its exerts the protective effect is not well established...
February 6, 2017: Biomolecules & Therapeutics
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