|
|
|
Comparative Proteomic Analysis Shows an Elevation of Mdh1 Associated with Hepatotoxicity Induced by Copper Nanoparticle in Rats |
DONG Shu-wei, GAO Zhao-hui, SHEN Xiao-yun, XUE Hui-wen , LI Xia |
1、Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture/Key Laboratory of New Animal Drug Project, Gansu Province/Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, P.R.China
2、Bijie College, Bijie 551700, P.R.China
3、College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, P.R.China |
|
|
摘要 Copper nanoparticle is a new material widely used in biological medicine, animal husbandry and industrial areas, but its potential toxicity to human health and environment remains unclear. In order to study the hepatotoxic mechanisms of nanoparticles copper, two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI/TOF MS) of proteomics technology were used to isolate and identify the differentially expressed proteins from liver, which associated with hepatotoxicity induced by copper nanoparticle in rats. In this study, we have screened 15 kinds of proteins related with hepatotoxicity, of which spot8212 was identified as Malate dehydrogenase (Mdh1). The mRNA expression trend of Mdh1 was consistent with the result of 2-DE by RT-PCR validation. Bioinformatics analysis showed that Mdh1 was stable and no signal peptides, subcellular location was in endoplasmic reticulum; it contained many functional sites such as malate dehydrogenase activity signal sites 155LTRLDHNRAKSQI167; α helixes and random coils were the two main elements. Homologous analysis demonstrated high homologous of Mdh1 in rats with mouse and human, and the phylogenetic tree of Mdh1 was constructed. The result indicated that copper nanoparticle could regulate up the Mdh1 protein expression so as to compensate the energy deficit. Energy metabolic disturbance may be a pathway for copper nanoparticle particles to exert the hepatotoxic effects in rats.
Abstract Copper nanoparticle is a new material widely used in biological medicine, animal husbandry and industrial areas, but its potential toxicity to human health and environment remains unclear. In order to study the hepatotoxic mechanisms of nanoparticles copper, two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI/TOF MS) of proteomics technology were used to isolate and identify the differentially expressed proteins from liver, which associated with hepatotoxicity induced by copper nanoparticle in rats. In this study, we have screened 15 kinds of proteins related with hepatotoxicity, of which spot8212 was identified as Malate dehydrogenase (Mdh1). The mRNA expression trend of Mdh1 was consistent with the result of 2-DE by RT-PCR validation. Bioinformatics analysis showed that Mdh1 was stable and no signal peptides, subcellular location was in endoplasmic reticulum; it contained many functional sites such as malate dehydrogenase activity signal sites 155LTRLDHNRAKSQI167; α helixes and random coils were the two main elements. Homologous analysis demonstrated high homologous of Mdh1 in rats with mouse and human, and the phylogenetic tree of Mdh1 was constructed. The result indicated that copper nanoparticle could regulate up the Mdh1 protein expression so as to compensate the energy deficit. Energy metabolic disturbance may be a pathway for copper nanoparticle particles to exert the hepatotoxic effects in rats.
|
Received: 13 December 2012
Accepted:
|
Fund: This work was supported by the Project of China Agriculture Research System (CARS-40-30). |
Corresponding Authors:
LI Xia, Tel: +86-931-2115291, E-mail: lanzhoulixia@126.com
E-mail: lanzhoulixia@126.com
|
About author: DONG Shu-wei, E-mail: dongshuwei2005@126.com |
Cite this article:
DONG Shu-wei, GAO Zhao-hui, SHEN Xiao-yun, XUE Hui-wen , LI Xia.
2014.
Comparative Proteomic Analysis Shows an Elevation of Mdh1 Associated with Hepatotoxicity Induced by Copper Nanoparticle in Rats. Journal of Integrative Agriculture, 13(5): 1073-1081.
|
Batra B, Lata S, Sharma M, Pundir C S. 2013. Anacrylamide biosensor based on immobilization of hemoglobin onto multiwalled carbon nanotube/copper nanoparticles/polyaniline hybrid film. AnalyticalBiochemistry, 433, 210-217Bradford M M. 1976. A rapid and sensitive method for the quantitation of microgram quantities of proteinutilizing the principle of protein-dye binding. AnalyticalBiochemistry, 72, 248-254Chen Y, Wang D, Zhu X, Zheng X, Feng L. 2012. Long-term effects of copper nanoparticles on wastewater biological nutrient removal and N2O generation in the activated sludge process. Environmental Science & Technology, 46, 12452-12458Chen Z, Meng H, Xing G, Chen C, Zhao Y, Jia G, WangT, Yuan H, Ye C, Zhao F, Chai Z, Zhu C, Fang X, MaB, Wan L. 2006. Acute toxicological effects of copper nanoparticles in vivo. Toxicology Letters, 163, 109-120Cioffi N, Ditaranto N, Torsi L, Picca R A, Sabbatini L,Valentini A, Novello L, Tantillo G, Bleve-Zacheo T,Zambonin P G. 2005. Analytical characterization of bioactive fluoropolymer ultra-thin coatings modifiedby copper nanoparticles. Analytical and Bioanalytical Chemistry, 381, 607-616Dong S W, Gao Z H, Shen X Y. 2012. Isolation,identification and bioinformatics analysis of CAT proteinrelated with hepatotoxity by copper nanoparticles in rats.Scientia Agricultura Sinica, 45, 2981-2990 (in Chinese)Dymov S I, Meek D J J, Steven B, Driscoll B T. 2004.Insertion of transpoon Tn5tac1 in the Sinorhizobium meliloti malate dehydrogenase (mdh) gene results in conditional polar effects on downstream TCA cycle genes. Molecular Plant-Microbe Interactions, 17, 1318-1327Feng W J, Guo B J, Yao Y Y, Peng H R, Sun Q X, Ni ZF. 2012. Proteomic identification of rhythmic proteins in maize seedling leaves. Journal of Integrative Agriculture, 11, 1958-1967Hinkelbein J, Feldmann R E, Kalenka A. 2010. Time-dependent alterations of cerebral proteins followingshort-term normobaric hyperoxia. Molecular AndCellular Biochemistry, 339, 9-21Khojasteh S C, Hartley D P, Ford K A, Uppal H, Oishi S,Nelson S D. 2012. Characterization of rat liver proteinsadducted by reactive metabolites of menthofuran.Chemical Research in Toxicology, 25, 2301-2309Lee S M, Dho S H, Ju S K, Maeng J S, Kim J Y, KwonK S. 2012. Cytosolic malate dehydrogenase regulates senescence in human fibroblasts. Biogerontology, 13,525-536Lei R, Wu C, Yang B, Ma H, Shi C, Wang Q, Wang Q,Yuan Y, Liao M. 2008. Integrated metabolomic analysisof the nano-sized copper particle-induced hepatotoxicityand nephrotoxicity in rats: A rapid in vivo screeningmethod for nanotoxicity. Toxicology and AppliedPharmacology, 232, 292-301Liao M, Liu H. 2012. Gene expression profiling of nephrotoxicity from copper nanoparticles in rats after repeated oral administration. Environmental Toxicologyand Pharmacology, 34, 67-80Liu G, Li X, Qin B, Xing D, Guo Y, Fan R. 2004.Investigation of the mending effect and mechanism of copper nano-particles on a tribologically stressedsurface. Tribology Letters, 17, 961-966Maynard A D, Warheit D B, Philbert M A. 2011. The newtoxicology of sophisticated materials: nanotoxicologyand beyond. Toxicological Sciences: An Official Journalof the Society of Toxicology, 120(Suppl. 1), S109-S129.Meng H, Chen Z, Xing G, Yuan H, Chen C, Zhao F,Zhang C, Zhao Y. 2007. Ultrahigh reactivity provokes nanotoxicity: Explanation of oral toxicity of nano-copperparticles. Toxicology Letters, 175, 102-110Minarik P, Tomaskova N, Kollarova M, Antalik M. 2002.Malate dehydrogenases-Structure and function. GeneralPhysiology And Biophysics, 21, 257-265Moghimi S M, Hunter A C, Murray J C. 2005.Nanomedicine: Current status and future prospects.The Journal of Federation of American Societies for Experimental Biology, 19, 311-330Nel A, Xia T, Madler L, Li N. 2006. Toxic potential of materials at the nanolevel. Science, 311, 622-627Oberdörster G, Maynard A, Donaldson K, Castranova V,Fitzpatrick J, Ausman K, Carter J, Karn B, Kreyling W,Lai D, Olin S, Monteiro-Riviere N, Warheit D, Yang H.2005. Principles for characterizing the potential humanhealth effects from exposure to nanomaterials: Elementsof a screening strategy. Particle and Fibre Toxicology, 2,doi: 10.1186/1743-8977-2-8Pennisi E 2012. BIOINFORMATICS. New way to look atlife. Science, 338, 317.Prabhu B M, Ali S F, Murdock R C, Hussain S M,Srivatsan M. 2010. Copper nanoparticles exert size andconcentration dependent toxicity on somatosensoryneurons of rat. Nanotoxicology, 4, 150-160Griffitt R J, Weil R, Hyndman K A, Denslow N D, PowersK, Taylor D, Barber D S. 2007. Exposure to copper nanoparticles causes gill injury and acute lethality in zebrafish (Danio rerio). Environmental Science & Technology, 41, 8178-8186 Tsoncheva T, Sarkadi-Priboczki E, Dimitrov M, Genova I. 2013. Nanostructured copper, chromium, and tin oxide multicomponent materials as catalysts for methanol decomposition: 11C-radiolabeling study. Journal of Colloid and Interface Science, 389, 244-251 Tylicki A, Kawalko A, Sokolska J, Strumilo S. 2007. Effect of anabolic steroid nandrolone decanoate on the properties of certain enzymes in the heart, liver, and muscle of rats, and their effect on rats’ cardiac electrophysiology. Hormone and Metabolic Research, 39, 268-272 Wang Y L. 2002. Effect of nano Cu and Cus04 on growth performance, diarrhrea incidence and digestion and approach to the mechanism in Weanling pigs. MSc thesis, Zhejiang University, China. (in Chinese) Wang Y, Yang B, Wu C, Zheng Z, Yuan Y, Hu Z, Ma H, Li S, Liao M, Wang Q. 2010. Plasma and liver proteomic analysis of 3Z-3-[(1H-pyrrol-2-yl)-methylidene]-1- (1-piperidinylmethyl)-1,3-2H-indol-2-one-in duced hepatotoxicity in Wistar rats Proteomics, 10, 2927- 2941. Wu J, Wang F, Gong Y, Li D, Sha J, Huang X, Han X. 2009. Proteomic analysis of changes induced by nonylphenol in Sprague-Dawley rat sertoli cells. Chemical Research in Toxicology, 22, 668-675 Yang B, Wang Q, Lei R, Wu C, Shi C, Wang Q, Yuan Y, Wang Y, Luo Y, Hu Z, Ma H, Liao M. 2010. Systems toxicology used in nanotoxicology: mechanistic insights into the hepatotoxicity of nano-copper particles from toxicogenomics. Journal of Nanoscience and Nanotechnology, 10, 8527-8537 Yin Y H, Guo Q M, Han Y, Wang L J, Wan S Q. 2012. Preparation, Characterization and nematicidal activity of lansiumamide B nano-capsules. Journal of Integrative Agriculture, 11, 1151-1158 |
No Suggested Reading articles found! |
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
|
Shared |
|
|
|
|
|
Discussed |
|
|
|
|