Login Register Cart 0
Generic placeholder image

Current Proteomics

Editor-in-Chief

ISSN (Print): 1570-1646
ISSN (Online): 1875-6247

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Curcumin Reverts the Protein Differential Expression in the Liver of the Diabetic Obese db/db Mice

Author(s): Oscar Gerardo Silva-Gaona, Juan Manuel Guzmán-Flores, Magdalena Hernández-Ortiz, Katya Vargas-Ortiz, Joel Ramírez-Emiliano, Sergio Encarnación-Guevara and Victoriano Pérez-Vázquez*

Volume 19, Issue 1, 2022

Published on: 14 January, 2021

Page: [39 - 50] Pages: 12

DOI: 10.2174/1570164618666210114112642

Price: $65

Abstract

Background: In type 2 diabetic mouse liver, hyperglycemia, and insulin modify gene expression. Curcumin is a powerful antioxidant and antidiabetic agent that regulates the gene expression of different signaling pathways through various transcription factors. Therefore, we hypothesized that curcumin modifies the protein expression profile in the liver of diabetic db/db mice.

Objective: To determine the effects of curcumin on the liver protein profile of diabetic db/db mice.

Methods: db/db and Wild Type (WT) male mice were allocated in four groups, and they were fed for eight weeks. Three WT and three diabetic db/db mice received a Standard Diet (SD; WT and db/db groups, respectively); three WT and three diabetic db/db mice received a SD supplemented with 0.75% (w/w) curcumin (WT+C and db/db+C groups, respectively). Liver proteins were separated by 2D electrophoresis. Differential protein expression analysis was performed on Image- Master 2D Platinum software, and selected proteins were identified by MALDI-TOF-MS and subjected to enrichment analysis using STRING and DAVID databases.

Results: Thirty-six proteins with differential expression due to diabetic background and curcumin treatment were found; these proteins participate in the metabolism of amino acids, carbohydrates, and lipids. Interestingly, the altered expression of seven proteins was prevented in the liver of the diabetic mice that received curcumin.

Conclusion: Among all differentially expressed proteins, curcumin reverted the altered expression of seven proteins. Thus, although it was observed that curcumin did not affect the biochemical parameters, it does modify the expression of some liver proteins in diabetic mice.

Keywords: Carbohydrate metabolism, curcumin, db/db mice, diabetes, liver proteome, obesity.

« Previous Next »
Graphical Abstract

[1]
Kaul, K.; Tarr, J.M.; Ahmad, S.I.; Kohner, E.M.; Chibber, R. Introduction to diabetes mellitus. Adv. Exp. Med. Biol., 2012, 771, 1-11.
[PMID: 23393665]
[2]
Castro, A.V.; Kolka, C.M.; Kim, S.P.; Bergman, R.N. Obesity, insulin resistance and comorbidities? Mechanisms of association. Arq. Bras. Endocrinol. Metabol, 2014, 58(6), 600-609.
[http://dx.doi.org/10.1590/0004-2730000003223] [PMID: 25211442]
[3]
Huang, X.; Yang, Z. Resistin’s, obesity and insulin resistance: the continuing disconnect between rodents and humans. J. Endocrinol. Invest., 2016, 39(6), 607-615.
[http://dx.doi.org/10.1007/s40618-015-0408-2] [PMID: 26662574]
[4]
Kim, G.H.; Park, E.C.; Yun, S.H.; Hong, Y.; Lee, D.G.; Shin, E.Y.; Jung, J.; Kim, Y.H.; Lee, K.B.; Jang, I.S.; Lee, Z.W.; Chung, Y.H.; Choi, J.S.; Cheong, C.; Kim, S.; Kim, S.I. Proteomic and bioinformatic analysis of membrane proteome in type 2 diabetic mouse liver. Proteomics, 2013, 13(7), 1164-1179.
[http://dx.doi.org/10.1002/pmic.201200210] [PMID: 23349036]
[5]
Pérez-Vázquez, V.; Guzmán-Flores, J.M.; Mares-Álvarez, D.; Hernández-Ortiz, M.; Macías-Cervantes, M.H.; Ramírez-Emiliano, J.; Encarnación-Guevara, S. Differential proteomic analysis of the pancreas of diabetic db/db mice reveals the proteins involved in the development of complications of diabetes mellitus. Int. J. Mol. Sci., 2014, 15(6), 9579-9593.
[http://dx.doi.org/10.3390/ijms15069579] [PMID: 24886809]
[6]
Guzmán-Flores, J.M.; Flores-Pérez, E.C.; Hernández-Ortíz, M.; López Briones, S.; Ramírez-Emiliano, J.; Encarnación-Guevara, S.; Pérez-Vázquez, V. Comparative Proteomics of Liver of the Diabetic Obese db/db and Non-Obese or Diabetic Mice. Curr. Proteomics, 2016, 13(3), 231-236.
[http://dx.doi.org/10.2174/1570164613666160722102430]
[7]
Martínez-Morúa, A.; Soto-Urquieta, M.G.; Franco-Robles, E.; Zúñiga-Trujillo, I.; Campos-Cervantes, A.; Pérez-Vázquez, V.; Ramírez-Emiliano, J. Curcumin decreases oxidative stress in mitochondria isolated from liver and kidneys of high-fat diet-induced obese mice. J. Asian Nat. Prod. Res., 2013, 15(8), 905-915.
[http://dx.doi.org/10.1080/10286020.2013.802687] [PMID: 23782307]
[8]
Soto-Urquieta, M.G.; López-Briones, S.; Pérez-Vázquez, V.; Saavedra-Molina, A.; González-Hernández, G.A.; Ramírez-Emiliano, J. Curcumin restores mitochondrial functions and decreases lipid peroxidation in liver and kidneys of diabetic db/db mice. Biol. Res., 2014, 47, 74.
[http://dx.doi.org/10.1186/0717-6287-47-74] [PMID: 25723052]
[9]
Aggarwal, B.B.; Sung, B. Pharmacological basis for the role of curcumin in chronic diseases: an age-old spice with modern targets. Trends Pharmacol. Sci., 2009, 30(2), 85-94.
[http://dx.doi.org/10.1016/j.tips.2008.11.002] [PMID: 19110321]
[10]
Ghosh, S.; Banerjee, S.; Sil, P. C. The beneficial role of curcumin on inflammation, diabetes and neurodegenerative disease: A recent update. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2015, 83, 111-124..
[11]
Franco-Robles, E.; Campos-Cervantes, A.; Murillo-Ortiz, B. O.; Segovia, J.; Lopez-Briones, S.; Vergara, P.; Perez-Vazquez, V.; Solis-Ortiz, M. S.; Ramirez-Emiliano, J. Effects of curcumin on brain-derived neurotrophic factor levels and oxidative damage in obesity and diabetes. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme, 2014, 39(2), 211-218..
[12]
Lee, S.J.; Kang, J.H.; Iqbal, W.; Kwon, O.S. Proteomic analysis of mice fed methionine and choline deficient diet reveals marker proteins associated with steatohepatitis. PLoS One, 2015, 10(4), e0120577.
[http://dx.doi.org/10.1371/journal.pone.0120577] [PMID: 25849376]
[13]
Panahi, Y.; Kianpour, P.; Mohtashami, R.; Jafari, R.; Simental- Mendía, L.E.; Sahebkar, A. Efficacy and Safety of Phytosomal Curcumin in Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Trial. Drug Res. (Stuttg.), 2017, 67(4), 244-251.
[http://dx.doi.org/10.1055/s-0043-100019] [PMID: 28158893]
[14]
Yang, Y.; Duan, W.; Lin, Y.; Yi, W.; Liang, Z.; Yan, J.; Wang, N.; Deng, C.; Zhang, S.; Li, Y.; Chen, W.; Yu, S.; Yi, D.; Jin, Z. SIRT1 activation by curcumin pretreatment attenuates mitochondrial oxidative damage induced by myocardial ischemia reperfusion injury. Free Radic. Biol. Med., 2013, 65, 667-679.
[http://dx.doi.org/10.1016/j.freeradbiomed.2013.07.007] [PMID: 23880291]
[15]
Rodgers, J.T.; Lerin, C.; Haas, W.; Gygi, S.P.; Spiegelman, B.M.; Puigserver, P. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature, 2005, 434(7029), 113-118.
[http://dx.doi.org/10.1038/nature03354] [PMID: 15744310]
[16]
Picard, F.; Auwerx, J. PPAR(gamma) and glucose homeostasis. Annu. Rev. Nutr., 2002, 22, 167-197.
[http://dx.doi.org/10.1146/annurev.nutr.22.010402.102808] [PMID: 12055342]
[17]
Jiménez-Flores, L.M.; López-Briones, S.; Macías-Cervantes, M.H.; Ramírez-Emiliano, J.; Pérez-Vázquez, V. A PPARγ, NF-κB and AMPK-dependent mechanism may be involved in the beneficial effects of curcumin in the diabetic db/db mice liver. Molecules, 2014, 19(6), 8289-8302.
[http://dx.doi.org/10.3390/molecules19068289] [PMID: 24945581]
[18]
Hurkman, W.J.; Tanaka, C.K. Solubilization of plant membrane proteins for analysis by two-dimensional gel electrophoresis. Plant Physiol., 1986, 81(3), 802-806.
[http://dx.doi.org/10.1104/pp.81.3.802] [PMID: 16664906]
[19]
O’Farrell, P.H. High resolution two-dimensional electrophoresis of proteins. J. Biol. Chem., 1975, 250(10), 4007-4021.
[PMID: 236308]
[20]
Candiano, G.; Bruschi, M.; Musante, L.; Santucci, L.; Ghiggeri, G.M.; Carnemolla, B.; Orecchia, P.; Zardi, L.; Righetti, P.G. Blue silver: a very sensitive colloidal Coomassie G-250 staining for proteome analysis. Electrophoresis, 2004, 25(9), 1327-1333.
[http://dx.doi.org/10.1002/elps.200305844] [PMID: 15174055]
[21]
Perkins, D.N.; Pappin, D.J.; Creasy, D.M.; Cottrell, J.S. Probability-based protein identification by searching sequence databases using mass spectrometry data. Electrophoresis, 1999, 20(18), 3551-3567.
[http://dx.doi.org/10.1002/(SICI)1522-2683(19991201)20:18<3551::AID-ELPS3551>3.0.CO;2-2] [PMID: 10612281]
[22]
UniProt Consortium. The Universal Protein Resource (UniProt) 2009. Nucleic Acids Res., 2009, 37(Database issue), D169-D174.
[PMID: 18836194]
[23]
Szklarczyk, D.; Franceschini, A.; Wyder, S.; Forslund, K.; Heller, D.; Huerta-Cepas, J.; Simonovic, M.; Roth, A.; Santos, A.; Tsafou, K.P.; Kuhn, M.; Bork, P.; Jensen, L.J.; von Mering, C. STRING v10: protein-protein interaction networks, integrated over the tree of life. Nucleic Acids Res., 2015, 43(Database issue), D447-D452.
[http://dx.doi.org/10.1093/nar/gku1003] [PMID: 25352553]
[24]
Huang, W.; Sherman, B.T.; Lempicki, R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc., 2009, 4(1), 44-57.
[http://dx.doi.org/10.1038/nprot.2008.211] [PMID: 19131956]
[25]
Weisberg, S.; Leibel, R.; Tortoriello, D.V. Proteasome inhibitors, including curcumin, improve pancreatic β-cell function and insulin sensitivity in diabetic mice. Nutr. Diabetes, 2016, 6, e205.
[http://dx.doi.org/10.1038/nutd.2016.13] [PMID: 27110686]
[26]
Seo, K.I.; Choi, M.S.; Jung, U.J.; Kim, H.J.; Yeo, J.; Jeon, S.M.; Lee, M.K. Effect of curcumin supplementation on blood glucose, plasma insulin, and glucose homeostasis related enzyme activities in diabetic db/db mice. Mol. Nutr. Food Res., 2008, 52(9), 995-1004.
[http://dx.doi.org/10.1002/mnfr.200700184] [PMID: 18398869]
[27]
Lu, M.; Yin, N.; Liu, W.; Cui, X.; Chen, S.; Wang, E. Curcumin Ameliorates Diabetic Nephropathy by Suppressing NLRP3 Inflammasome Signaling. BioMed Res. Int., 2017, 2017, 1516985.
[http://dx.doi.org/10.1155/2017/1516985] [PMID: 28194406]
[28]
Bi, X.; Henry, C.J. Plasma-free amino acid profiles are predictors of cancer and diabetes development. Nutr. Diabetes, 2017, 7(3), e249.
[http://dx.doi.org/10.1038/nutd.2016.55] [PMID: 28287627]
[29]
Nie, C.; He, T.; Zhang, W.; Zhang, G.; Ma, X. Branched Chain Amino Acids: Beyond Nutrition Metabolism. Int. J. Mol. Sci., 2018, 19(4), E954.
[http://dx.doi.org/10.3390/ijms19040954] [PMID: 29570613]
[30]
Hu, S.; Han, M.; Rezaei, A.; Li, D.; Wu, G.; Ma, X. L-Arginine Modulates Glucose and Lipid Metabolism in Obesity and Diabetes. Curr. Protein Pept. Sci., 2017, 18(6), 599-608.
[http://dx.doi.org/10.2174/1389203717666160627074017] [PMID: 27356939]
[31]
Gray, L.R.; Tompkins, S.C.; Taylor, E.B. Regulation of pyruvate metabolism and human disease. Cell. Mol. Life Sci., 2014, 71(14), 2577-2604.
[http://dx.doi.org/10.1007/s00018-013-1539-2] [PMID: 24363178]
[32]
Jeoung, N.H.; Harris, C.R.; Harris, R.A. Regulation of pyruvate metabolism in metabolic-related diseases. Rev. Endocr. Metab. Disord., 2014, 15(1), 99-110.
[http://dx.doi.org/10.1007/s11154-013-9284-2] [PMID: 24214243]
[33]
Nikiforova, V.J.; Giesbertz, P.; Wiemer, J.; Bethan, B.; Looser, R.; Liebenberg, V.; Ruiz Noppinger, P.; Daniel, H.; Rein, D. Glyoxylate, a new marker metabolite of type 2 diabetes. J. Diabetes Res., 2014, 2014, 685204.
[http://dx.doi.org/10.1155/2014/685204] [PMID: 25525609]
[34]
Giesbertz, P.; Padberg, I.; Rein, D.; Ecker, J.; Höfle, A.S.; Spanier, B.; Daniel, H. Metabolite profiling in plasma and tissues of ob/ob and db/db mice identifies novel markers of obesity and type 2 diabetes. Diabetologia, 2015, 58(9), 2133-2143.
[http://dx.doi.org/10.1007/s00125-015-3656-y] [PMID: 26058503]
[35]
Padberg, I.; Peter, E.; González-Maldonado, S.; Witt, H.; Mueller, M.; Weis, T.; Bethan, B.; Liebenberg, V.; Wiemer, J.; Katus, H.A.; Rein, D.; Schatz, P. A new metabolomic signature in type-2 diabetes mellitus and its pathophysiology. PLoS One, 2014, 9(1), e85082.
[http://dx.doi.org/10.1371/journal.pone.0085082] [PMID: 24465478]
[36]
Lodhi, I.J.; Semenkovich, C.F. Peroxisomes: a nexus for lipid metabolism and cellular signaling. Cell Metab., 2014, 19(3), 380-392.
[http://dx.doi.org/10.1016/j.cmet.2014.01.002] [PMID: 24508507]
[37]
Turecký, L.; Kupčová, V.; Uhlíková, E.; Mojto, V. Peroxisomal enzymes in the liver of rats with experimental diabetes mellitus type 2. Physiol. Res., 2014, 63(Suppl. 4), S585-S591.
[http://dx.doi.org/10.33549/physiolres.932918] [PMID: 25669689]
[38]
Wu, Y.; Williams, E.G.; Dubuis, S.; Mottis, A.; Jovaisaite, V.; Houten, S.M.; Argmann, C.A.; Faridi, P.; Wolski, W.; Kutalik, Z.; Zamboni, N.; Auwerx, J.; Aebersold, R. Multilayered genetic and omics dissection of mitochondrial activity in a mouse reference population. Cell, 2014, 158(6), 1415-1430.
[http://dx.doi.org/10.1016/j.cell.2014.07.039] [PMID: 25215496]
[39]
Chae, S.; Kim, S.J.; Do Koo, Y.; Lee, J.H.; Kim, H.; Ahn, B.Y.; Ha, Y.C.; Kim, Y.H.; Jang, M.G.; Koo, K.H.; Choi, S.H.; Lim, S.; Park, Y.J.; Jang, H.C.; Hwang, D.; Lee, S.W.; Park, K.S. A mitochondrial proteome profile indicative of type 2 diabetes mellitus in skeletal muscles. Exp. Mol. Med., 2018, 50(9), 129.
[http://dx.doi.org/10.1038/s12276-018-0154-6] [PMID: 30266947]
[40]
Hui, X.; Zhu, W.; Wang, Y.; Lam, K.S.; Zhang, J.; Wu, D.; Kraegen, E.W.; Li, Y.; Xu, A. Major urinary protein-1 increases energy expenditure and improves glucose intolerance through enhancing mitochondrial function in skeletal muscle of diabetic mice. J. Biol. Chem., 2009, 284(21), 14050-14057.
[http://dx.doi.org/10.1074/jbc.M109.001107] [PMID: 19336396]
[41]
Ge, Q.; Zhang, S.; Chen, L.; Tang, M.; Liu, L.; Kang, M.; Gao, L.; Ma, S.; Yang, Y.; Lv, P.; Kong, M.; Yao, Q.; Feng, F.; Chen, K. Mulberry Leaf Regulates Differentially Expressed Genes in Diabetic Mice Liver Based on RNA-Seq Analysis. Front. Physiol., 2018, 9, 1051.
[http://dx.doi.org/10.3389/fphys.2018.01051] [PMID: 30131712]
[42]
Rohm, M.; Savic, D.; Ball, V.; Curtis, M.K.; Bonham, S.; Fischer, R.; Legrave, N.; MacRae, J.I.; Tyler, D.J.; Ashcroft, F.M. Cardiac Dysfunction and Metabolic Inflexibility in a Mouse Model of Diabetes Without Dyslipidemia. Diabetes, 2018, 67(6), 1057-1067.
[http://dx.doi.org/10.2337/db17-1195] [PMID: 29610263]
[43]
Nyalwidhe, J.O.; Grzesik, W.J.; Burch, T.C.; Semeraro, M.L.; Waseem, T.; Gerling, I.C.; Mirmira, R.G.; Morris, M.A.; Nadler, J.L. Comparative quantitative proteomic analysis of disease stratified laser captured microdissected human islets identifies proteins and pathways potentially related to type 1 diabetes. PLoS One, 2017, 12(9), e0183908.
[http://dx.doi.org/10.1371/journal.pone.0183908] [PMID: 28877242]
[44]
Xie, X.; Yi, Z.; Sinha, S.; Madan, M.; Bowen, B.P.; Langlais, P.; Ma, D.; Mandarino, L.; Meyer, C. Proteomics analyses of subcutaneous adipocytes reveal novel abnormalities in human insulin resistance. Obesity (Silver Spring), 2016, 24(7), 1506-1514.
[http://dx.doi.org/10.1002/oby.21528] [PMID: 27345962]
[45]
Ponsuksili, S.; Trakooljul, N.; Hadlich, F.; Haack, F.; Murani, E.; Wimmers, K. Genetically regulated hepatic transcripts and pathways orchestrate haematological, biochemical and body composition traits. Sci. Rep., 2016, 6, 39614.
[http://dx.doi.org/10.1038/srep39614] [PMID: 28000754]
[46]
Karthik, D.; Ravikumar, S. Characterization of the brain proteome of rats with diabetes mellitus through two-dimensional electrophoresis and mass spectrometry. Brain Res., 2011, 1371, 171-179.
[http://dx.doi.org/10.1016/j.brainres.2010.11.066] [PMID: 21112318]
[47]
Farrell, D.H. Pathophysiologic roles of the fibrinogen gamma chain. Curr. Opin. Hematol., 2004, 11(3), 151-155.
[http://dx.doi.org/10.1097/01.moh.0000131440.02397.a4] [PMID: 15257013]

Rights & Permissions Print Cite
Article Metrics
29
1
© 2024 Bentham Science Publishers | Privacy Policy