Please wait a minute...
Journal of Integrative Agriculture  2014, Vol. 13 Issue (5): 1073-1081    DOI: 10.1016/S2095-3119(13)60389-5
Animal Science · Veterinary Science Advanced Online Publication | Current Issue | Archive | Adv Search |
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
Download:  PDF in ScienceDirect  
Export:  BibTeX | EndNote (RIS)      
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.
Keywords:  copper nanoparticle       hepatotoxicity       proteomics       malate dehydrogenase       bioinformatics       rat  
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, 210-217

Bradford M M. 1976. A rapid and sensitive method for the quantitation of microgram quantities of proteinutilizing the principle of protein-dye binding. AnalyticalBiochemistry, 72, 248-254

Chen 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, 12452-12458

Chen 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, 109-120

Cioffi 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, 607-616

Dong 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, 1318-1327

Feng 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, 1958-1967

Hinkelbein J, Feldmann R E, Kalenka A. 2010. Time-dependent alterations of cerebral proteins followingshort-term normobaric hyperoxia. Molecular AndCellular Biochemistry, 339, 9-21

Khojasteh 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, 2301-2309

Lee 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, 13,525-536

Lei 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, 292-301

Liao M, Liu H. 2012. Gene expression profiling of nephrotoxicity from copper nanoparticles in rats after repeated oral administration. Environmental Toxicologyand Pharmacology, 34, 67-80

Liu 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, 961-966

Maynard 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, 102-110

Minarik P, Tomaskova N, Kollarova M, Antalik M. 2002.Malate dehydrogenases-Structure and function. GeneralPhysiology And Biophysics, 21, 257-265

Moghimi 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, 311-330

Nel A, Xia T, Madler L, Li N. 2006. Toxic potential of materials at the nanolevel. Science, 311, 622-627

Oberdörster 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: 10.1186/1743-8977-2-8

Pennisi 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, 150-160

Griffitt 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
[1] CHU Jin-peng, GUO Xin-hu, ZHENG Fei-na, ZHANG Xiu, DAI Xing-long, HE Ming-rong. Effect of delayed sowing on grain number, grain weight, and protein concentration of wheat grains at specific positions within spikes[J]. >Journal of Integrative Agriculture, 2023, 22(8): 2359-2369.
[2] WANG Xing-long, ZHU Yu-peng, YAN Ye, HOU Jia-min, WANG Hai-jiang, LUO Ning, WEI Dan, MENG Qing-feng, WANG Pu. Irrigation mitigates the heat impacts on photosynthesis during grain filling in maize [J]. >Journal of Integrative Agriculture, 2023, 22(8): 2370-2383.
[3] SU Qin, LÜ Jun, LI Wan-xue, CHEN Wei-wen, LUO Min-shi, ZHANG Chuan-chuan, ZHANG Wen-qing. The combination of NlMIP and Gαi/q coupled-receptor NlA10 promotes abdominal vibration production in female Nilaparvata lugens (Stål)[J]. >Journal of Integrative Agriculture, 2023, 22(8): 2470-2482.
[4] ZHANG Qiang-qiang, GAO Xi-xi, Nazir Muhammad ABDULLAHI, WANG Yue, HUO Xue-xi. Asset specificity and farmers’ intergenerational succession willingness of apple management[J]. >Journal of Integrative Agriculture, 2023, 22(8): 2553-2566.
[5] XU Yan-xia, ZHANG Jing, WAN Zi-yun, HUANG Shan-xia, DI Hao-chen, HE Ying, JIN Song-heng. Physiological and transcriptome analyses provide new insights into the mechanism mediating the enhanced tolerance of melatonin-treated rhododendron plants to heat stress[J]. >Journal of Integrative Agriculture, 2023, 22(8): 2397-2411.
[6] GAO Song-juan, LI Shun, ZHOU Guo-peng, CAO Wei-dong. The potential of green manure to increase soil carbon sequestration and reduce the yield-scaled carbon footprint of rice production in southern China[J]. >Journal of Integrative Agriculture, 2023, 22(7): 2233-2247.
[7] CHEN Guang-yi, PENG Li-gong, LI Cong-mei, TU Yun-biao, LAN Yan, WU Chao-yue, DUAN Qiang, ZHANG Qiu-qiu, YANG Hong, LI Tian. Effects of the potassium application rate on lipid synthesis and eating quality of two rice cultivars[J]. >Journal of Integrative Agriculture, 2023, 22(7): 2025-2040.
[8] LIU Zhen-yu, LI Yi-yang, Leila. I. M. TAMBEL, LIU Yu-ting, DAI Yu-yang, XU Ze, LENG Xin-hua, ZHANG Xiang, CHEN De-hua, CHEN Yuan. Enhancing boll protein synthesis and carbohydrate conversion by the application of exogenous amino acids at the peak flowering stage increased the boll Bt toxin concentration and lint yield in cotton[J]. >Journal of Integrative Agriculture, 2023, 22(6): 1684-1694.
[9] CHANG Fang-di, WANG Xi-quan, SONG Jia-shen, ZHANG Hong-yuan, YU Ru, WANG Jing, LIU Jian, WANG Shang, JI Hong-jie, LI Yu-yi. Maize straw application as an interlayer improves organic carbon and total nitrogen concentrations in the soil profile: A four-year experiment in a saline soil[J]. >Journal of Integrative Agriculture, 2023, 22(6): 1870-1882.
[10] WANG Peng, WANG Cheng-dong, WANG Xiao-lin, WU Yuan-hua, ZHANG Yan, SUN Yan-guo, SHI Yi, MI Guo-hua. Increasing nitrogen absorption and assimilation ability under mixed NO3 and NH4+ supply is a driver to promote growth of maize seedlings[J]. >Journal of Integrative Agriculture, 2023, 22(6): 1896-1908.
[11] ZHAO Xiao-dong, QIN Xiao-rui, LI Ting-liang, CAO Han-bing, XIE Ying-he. Effects of planting patterns plastic film mulching on soil temperature, moisture, functional bacteria and yield of winter wheat in the Loess Plateau of China[J]. >Journal of Integrative Agriculture, 2023, 22(5): 1560-1573.
[12] XIE Si-han, WANG Zhao-jun, HE Zhi-yong, ZENG Mao-mao, QIN Fang, Benu ADHIKARI, CHEN Jie. The effects of maltodextrin/starch in soy protein isolate–wheat gluten on the thermal stability of high-moisture extrudates[J]. >Journal of Integrative Agriculture, 2023, 22(5): 1590-1602.
[13] GAO Yue, LUO Jian, SUN Yue, ZHANG Hua-wei, ZHANG Da-xia, LIU Feng, MU Wei, LI Bei-xing. Photosensitivity and a precise combination of size-dependent lambda-cyhalothrin microcapsules synergistically generate better insecticidal efficacy [J]. >Journal of Integrative Agriculture, 2023, 22(5): 1477-1488.
[14] YU Feng-hua, BAI Ju-chi, JIN Zhong-yu, GUO Zhong-hui, YANG Jia-xin, CHEN Chun-ling. Combining the critical nitrogen concentration and machine learning algorithms to estimate nitrogen deficiency in rice from UAV hyperspectral data[J]. >Journal of Integrative Agriculture, 2023, 22(4): 1216-1229.
[15] YANG Ning, YANG Dan-dan, YU Xu-chen, XU Cao. Multi-omics-driven development of alternative crops for natural rubber production[J]. >Journal of Integrative Agriculture, 2023, 22(4): 959-971.
No Suggested Reading articles found!