The fluoride has volcanic activity and abundantly exists in environment combining with other elements as fluoride compounds. Recent researches indicated that the molecular mechanisms of intracellular fluoride toxicity were very complex. However, the molecular mechanisms underlying the effects on gene expression of chronic fluoride-induced damage is unknown, especially the detailed regulatory process of mitochondria. In the present study, we screened the differential expression ESTs associated with fluorosis by DDRT-PCR in rat liver. We gained 8 genes, 3 new ESTs, and 1 unknown function sequence and firstly demonstrated that microsomal glutathione S-transferase 1 (MGST1), ATP synthase H+ transporting mitochondrial F0 complex subunit C1, selenoprotein S, mitochondrial IF1 protein, and mitochondrial succinyl-CoA synthetase alpha subunit were participated in mitochondria metabolism, functional and structural damage process caused by chronic fluorosis. This information will be very helpful for understanding the molecular mechanisms of fluorosis. 1. Introduction The fluoride has volcanic activity and abundantly exists in environment combining with other elements as fluoride compounds. With the development of the world economy, more and more organofluorine compounds are increasingly used. These compounds have a wide range of functions and can serve as agrochemicals, pharmaceuticals, refrigerants, pesticides, surfactants, fire-extinguishing agents, fibers, membranes, ozone depletors, and insulating materials [1, 2]. At the same time, in last decade, the fluoride effects have resurfaced due to the awareness that this element interacts with cellular systems even at low doses. Excessive fluoride intake over a long period of time may result in a serious public health problem called fluorosis, which is characterized by dental mottling and skeletal manifestations such as crippling deformities, osteoporosis, and osteosclerosis [3]. In recent years, metabolic, functional, and structural damage caused by chronic fluorosis have been reported in many tissues. Fluoride can induce oxidative stress and modulate intracellular redox homeostasis, lipid peroxidation, and protein carbonyl content, as well as alter gene expression and cause apoptosis. Genes modulated by fluoride include those related to the stress response metabolic enzymes, the cell-cell communications, and signal transduction [1]. In most cases, fluoride acts as an enzyme inhibitor, but fluoride ions can occasionally stimulate enzyme activity. Research data strongly suggest that fluoride inhibits protein
References
[1]
O. Barbier, L. Arreola-Mendoza, and L. M. Del Razo, “Molecular mechanisms of fluoride toxicity,” Chemico-Biological Interactions, vol. 188, no. 2, pp. 319–333, 2010.
[2]
L. H. Weinstein and A. Davidson, Fluorides in the Environment. Effects on Plants and Animals, CABI Publishing, Oxford, UK, 2004.
[3]
E. T. Urbansky, “Fate of fluorosilicate drinking water additives,” Chemical Reviews, vol. 102, no. 8, pp. 2837–2854, 2002.
[4]
H. Karube, G. Nishitai, K. Inageda, H. Kurosu, and M. Matsuoka, “NaF activates MAPKs and induces apoptosis in odontoblast-like cells,” Journal of Dental Research, vol. 88, no. 5, pp. 461–465, 2009.
[5]
Y. Zhang, W. Li, H. S. Chi, J. Chen, and P. K. DenBesten, “JNK/c-Jun signaling pathway mediates the fluoride-induced down-regulation of MMP-20 in vitro,” Matrix Biology, vol. 26, no. 8, pp. 633–641, 2007.
[6]
M. Zhang, A. Wang, T. Xia, and P. He, “Effects of fluoride on DNA damage, S-phase cell-cycle arrest and the expression of NF-κB in primary cultured rat hippocampal neurons,” Toxicology Letters, vol. 179, no. 1, pp. 1–5, 2008.
[7]
C. D. Anuradha, S. Kanno, and S. Hirano, “Oxidative damage to mitochondria is a preliminary step to caspase-3 activation in fluoride-induced apoptosis in HL-60 cells,” Free Radical Biology and Medicine, vol. 31, no. 3, pp. 367–373, 2001.
[8]
M. L. Cittanova, B. Lelongt, M. C. Verpont et al., “Fluoride ion toxicity in human kidney collecting duct cells,” Anesthesiology, vol. 84, no. 2, pp. 428–435, 1996.
[9]
E. Dabrowska, M. Balunowska, R. Letko, and B. Szynaka, “Ultrastructural study of the mitochondria in the submandibular gland, the pancreas and the liver of young rats, exposed to NaF in drinking water,” Roczniki Akademii Medycznej w Bialymstoku, vol. 49, pp. 180–181, 2004.
[10]
N. Imaizumi, S. Miyagi, and Y. Aniya, “Reactive nitrogen species derived activation of rat liver microsomal glutathione S-transferase,” Life Sciences, vol. 78, no. 26, pp. 2998–3006, 2006.
[11]
S. Zhao, S. L. Ooi, and A. B. Pardee, “New primer strategy improves precision of differential display,” BioTechniques, vol. 18, no. 5, pp. 842–850, 1995.
[12]
Q. S. Hossain, E. Ulziikhishig, K. K. Lee, H. Yamamoto, and Y. Aniya, “Contribution of liver mitochondrial membrane-bound glutathione transferase to mitochondrial permeability transition pores,” Toxicology and Applied Pharmacology, vol. 235, no. 1, pp. 77–85, 2009.
[13]
C. Andersson, E. Mosialou, R. Weinander, and R. Morgenstern, “Enzymology of microsomal glutathione S-transferase,” Advances in Pharmacology, vol. 27, no. C, pp. 19–35, 1994.
[14]
Y. Aniya and M. W. Anders, “Regulation of rat liver microsomal glutathione S-tranferase activity by thiol/disulfide exchange,” Archives of Biochemistry and Biophysics, vol. 270, no. 1, pp. 330–334, 1989.
[15]
M. Shimoji, Y. Aniya, and R. Morgenstern, “Activation of microsomal glutathione transferase 1,” in Toxicology of Glutathione Transferases, Y. C. Awasthi, Ed., pp. 293–319, Taylor & Francis, New York, NY, USA, 2007.
[16]
K. K. Lee, M. Shimoji, Q. S. Hossain, H. Sunakawa, and Y. Aniya, “Novel function of glutathione transferase in rat liver mitochondrial membrane: role for cytochrome c release from mitochondria,” Toxicology and Applied Pharmacology, vol. 232, no. 1, pp. 109–118, 2008.
[17]
R. Rinaldi, Y. Aniya, R. Svensson et al., “NADPH dependent activation of microsomal glutathione transferase,” Chemico-Biological Interactions, vol. 147, no. 2, pp. 163–172, 2004.
[18]
R. Mangiullo, A. Gnoni, F. Damiano et al., “3,5-diiodo-L-thyronine upregulates rat-liver mitochondrial F0F1-ATP synthase by GA-binding protein/nuclear respiratory factor-2,” Biochimica et Biophysica Acta, vol. 1797, no. 2, pp. 233–240, 2010.
[19]
S. Papa, F. Guerrieri, F. Zanotti, M. Fiermonte, G. Capozza, and E. Jirillo, “The γ subunit of F1 and the PVP protein of F0 (F0I) are components of the gate of mitochondrial F0F1H+-ATP synthase,” FEBS Letters, vol. 272, no. 1-2, pp. 117–120, 1990.
[20]
J. A. Berden and A. F. Hartog, “Analysis of the nucleotide binding sites of mitochondrial ATP synthase provides evidence for a two-site catalytic mechanism,” Biochimica et Biophysica Acta, vol. 1458, no. 2-3, pp. 234–251, 2000.
[21]
T. Xu, F. Zanotti, A. Gaballo, G. Raho, and S. Papa, “F1 and F0 connections in the bovine mitochondrial ATP synthase. The role of the of α subunit N-terminus, oligomycin-sensitivity conferring protein (OCSP) and subunit d,” European Journal of Biochemistry, vol. 267, no. 14, pp. 4445–4455, 2000.
[22]
R. P. Hafner, G. C. Brown, and M. D. Brand, “Thyroid-hormone control of state-3 respiration in isolated rat liver mitochondria,” Biochemical Journal, vol. 265, no. 3, pp. 731–734, 1990.
[23]
F. Guerrieri, M. Kalous, E. Adorisio et al., “Hypothyroidism leads to a decreased expression of mitochondrial F0F1- ATP synthase in rat liver,” Journal of Bioenergetics and Biomembranes, vol. 30, no. 3, pp. 269–276, 1998.
[24]
T. Andrianaivomananjaona, M. Moune-Dimala, S. Herga, V. David, and F. Haraux, “How the N-terminal extremity of Saccharomyces cerevisiae IF1 interacts with ATP synthase: a kinetic approach,” Biochimica et Biophysica Acta, vol. 1807, no. 2, pp. 197–204, 2011.
[25]
M. E. Pullman and G. C. Monroy, “A naturally occurring inhibitor of mitochondrial adenosine,” The Journal of Biological Chemistry, vol. 238, pp. 3762–3769, 1963.
[26]
M. Satre, M. B. de Jerphanion, J. Huet, and P. V. Vignais, “ATPase inhibitor from yeast mitochondria. Purification and properties,” Biochimica et Biophysica Acta, vol. 387, no. 2, pp. 241–255, 1975.
[27]
H. Matsubara, T. Hase, T. Hashimoto, and K. Tagawa, “Amino acid sequence of an intrinsic inhibitor of mitochondrial ATPase from yeast,” Journal of Biochemistry, vol. 90, no. 4, pp. 1159–1165, 1981.
[28]
B. Norling, C. Tourikas, B. Hamasur, and E. Glaser, “Evidence for an endogenous ATPase inhibitor protein in plant mitochondria. Purification and characterization,” European Journal of Biochemistry, vol. 188, no. 2, pp. 247–252, 1990.
[29]
K. E. Polgreen, J. Featherstone, A. C. Willis, and D. A. Harris, “Primary structure and properties of the inhibitory protein of the mitochondrial ATPase (H+-ATP synthase) from potato,” Biochimica et Biophysica Acta, vol. 1229, no. 2, pp. 175–180, 1995.
[30]
E. Cabezón, M. J. Runswick, A. G. W. Leslie, and J. E. Walker, “The structure of bovine IF1, the regulatory subunit of mitochondrial F-ATPase,” EMBO Journal, vol. 20, no. 24, pp. 6990–6996, 2002.
[31]
A. C. Dianoux, A. Tsugita, G. Klein, and P. V. Vignais, “Effects of proteolytic fragmentations on the activity of the mitochondrial natural ATPase inhibitor,” FEBS Letters, vol. 140, no. 2, pp. 223–228, 1982.
[32]
J. S. Stout, B. E. Partridge, D. A. Dibbern, and S. M. Schuster, “Peptide analogs of the beef heart mitochondrial F1-ATPase inhibitor protein,” Biochemistry, vol. 32, no. 29, pp. 7496–7502, 1993.
[33]
M. J. van Raaij, G. L. Orriss, M. G. Montgomery et al., “The ATPase inhibitor protein from bovine heart mitochondria: the minimal inhibitory sequence,” Biochemistry, vol. 35, no. 49, pp. 15618–15625, 1996.
[34]
M. S. Lebowitz and P. L. Pedersen, “Protein inhibitor of mitochondrial ATP synthase: relationship of inhibitor structure to pH-dependent regulation,” Archives of Biochemistry and Biophysics, vol. 330, no. 2, pp. 342–354, 1996.
[35]
R. Venard, D. Brèthes, M. F. Giraud, J. Vaillier, J. Velours, and F. Haraux, “Investigation of the role and mechanism of IF1 and STF1 proteins, twin inhibitory peptides which interact with the yeast mitochondrial ATP synthase,” Biochemistry, vol. 42, no. 24, pp. 7626–7636, 2003.
[36]
M. Campanella, A. Seraphim, R. Abeti, E. Casswell, P. Echave, and M. R. Duchen, “IF1, the endogenous regulator of the F1Fo-ATPsynthase, defines mitochondrial volume fraction in HeLa cells by regulating autophagy,” Biochimica et Biophysica Acta, vol. 1787, no. 5, pp. 393–401, 2009.
[37]
D. Phillips, A. M. Aponte, S. A. French, D. J. Chess, and R. S. Balaban, “Succinyl-CoA synthetase is a phosphate target for the activation of mitochondrial metabolism,” Biochemistry, vol. 48, no. 30, pp. 7140–7149, 2009.
[38]
S. Kaufman, C. Gilvarg, O. Cori, and S. Ochoa, “Enzymatic oxidation of alpha-ketoglutarate and coupled phosphorylation,” Journal of Biological Chemistry, vol. 203, pp. 869–888, 1953.
[39]
M. E. Fraser, M. N. G. James, W. A. Bridger, and W. T. Wolodko, “Phosphorylated and dephosphorylated structures of pig heart, GTP-specific succinyl-CoA synthetase,” Journal of Molecular Biology, vol. 299, no. 5, pp. 1325–1339, 2000.
[40]
S. J. Holt and D. L. Riddle, “SAGE surveys C. elegans carbohydrate metabolism: evidence for an anaerobic shift in the long-lived dauer larva,” Mechanisms of Ageing and Development, vol. 124, no. 7, pp. 779–800, 2003.
[41]
J. M. Weinberg, M. A. Venkatachalam, N. F. Roeser, and I. Nissim, “Mitochondrial dysfunction during hypoxia/reoxygenation and its correction by anaerobic metabolism of citric acid cycle intermediates,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 6, pp. 2826–2831, 2000.
[42]
E. Basso, V. Petronilli, M. A. Forte, and P. Bernardi, “Phosphate is essential for inhibition of the mitochondrial permeability transition pore by cyclosporin A and by cyclophilin D ablation,” Journal of Biological Chemistry, vol. 283, no. 39, pp. 26307–26311, 2008.
[43]
J. S. R. Zavala, J. P. Pardo, and R. M. Sanchez, “Modulation of 2-oxoglutarate dehydrogenase complex by inorganic phosphate, Mg2+, and other effectors,” Archives of Biochemistry and Biophysics, vol. 379, no. 1, pp. 78–84, 2000.
[44]
M. Olsson, B. Olsson, P. Jacobson et al., “Expression of the selenoprotein S (SELS) gene in subcutaneous adipose tissue and SELS genotype are associated with metabolic risk factors,” Metabolism: Clinical and Experimental, vol. 60, no. 1, pp. 114–120, 2011.
[45]
K. H. Kim, Y. Gao, K. Walder, G. R. Collier, J. Skelton, and A. H. Kissebah, “SEPS1 protects RAW264.7 cells from pharmacological ER stress agent-induced apoptosis,” Biochemical and Biophysical Research Communications, vol. 354, no. 1, pp. 127–132, 2007.
[46]
J. E. Curran, J. B. M. Jowett, K. S. Elliott et al., “Genetic variation in selenoprotein S influences inflammatory response,” Nature Genetics, vol. 37, no. 11, pp. 1234–1241, 2005.
