Abstract
The alteration in calcium transport in the liver nuclei of rats orally administered carbon tetrachloride (CCl4) was investigated. Rats received a single oral administration of CCl4(5, 10, and 25%, 1.0ml/100 g body weight), and 5, 24 and 48 h later the animals were sacrificed. The administration of CCl4 (25%) caused a remarkable elevetion of calcium content in the liver tissues and the nuclei of rats. Liver nuclear Ca2+-ATPase activity was markedly decreased by CCl4 (25%) administration. The presence of dibutyryl cyclic AMP(10-4 and 10-3 M) or inositol 1,4,5-trisphosphate (10-6 and 10-5 M) in the enzyme reaction mixture caused a significant decrease in Ca2+-ATPase activity in the liver nuclei obtained from normal rat, while the enzyme activity was significantly increased by calmodulin (1.0 and 2.0 μg/ml). These signaling factor's effects were completely impaired in the liver nuclei obtained from CCl4 (25%)-administered rats. DNA fragmentation in the liver nuclei obtained from CCl4 -administered rats was significantly decreased by the presence of EGTA (2 mM) in the reaction mixture, suggesting that the endogenous calcium activates nuclear DNA fragmentation. The present study demonstrates that calcium transport system in the liver nuclei is impaired by liver injury with CCl4 administration in rats.
Similar content being viewed by others
References
Reinhart PH, Taylor WM, Bygrave FL: The role of calcium ions in the mechanisms of action of α-adrenergic agonists in rat liver. Biochem J 233: 1–13, 1984
Kraus-Friedmam N, Feng L: The role of intracellular Ca2+ in the regulation of gluconeogenesis. Metabolism 48: 389–403, 1996
Cruise J, Honck KA, Michalopoulis GK: Induction of DNA synthesis in cultured rat hepatocytes through stimulation of α-adrenoreceptor by norepinephrine. Nature 227: 749–751, 1985
Bachs O, Carafolli E: Calmodulin and calmodulin-binding proteins in liver cell nuclei. J Biol Chem 262: 10786–10790, 1987
Pujol MJ, Soriano M, Alique R, Carafolli E, Backs O: Effect of α-adrenergic blockers on calmodulin association with the nuclear matrix of rat liver cells during proliferative activation. J Biol Chem 264: 18863–18865, 1989
Jones DP, McConkey DJ, Nicotera P, Orrenius S: Calcium activated DNA fragmentation in rat liver nuclei. J Biol Chem 264: 6398–6403, 1989
Backs O, Lanini L, Serratosa J, Coll MJ, Bastors R, Aline R, Rius E, Carafolli E: Calmodulin-binding proteins in the nuclei of quiescent and proliferatively activated rat liver cells. J Biol Chem 265: 18595–18600, 1990
Allbritton NL, Oancea E, Kuhn MA, Meyer T: Source of nuclear calcium signals. Proc Natl Acad Sci USA 91: 12458–12462, 1994
Nicotera P, McConkey DJ, Jones DP, Orrenius S: ATP stimulates Ca2+ uptake and increases the free Ca2+ concentration in isolated rat liver nuclei. Proc Natl Acad Sci USA 86: 453–457, 1989
Yamaguchi M, Oishi K: Characterization of Ca2+-stimulated adenosine 5′-triphosphatase and Ca2+ sequestering in rat liver nuclei. Mol Cell Biochem 125: 43–49, 1993
Humbert J-P, Matter N, Artault J-C, Koppler P, Malviya AN: Inositol 1,4, 5-trisphosphate receptor is located to the inner nuclear membrane indicating regulation of nuclear calcium signaling by inositol 1, 4, 5-trisphosphate. Discrete distribution of inositol phosphate receptors to inner and outer nuclear membranes. J Biol Chem 271: 478–485, 1996
Yamaguchi M, Tai H: Inhibitory effect of calcium-binding protein regucalcin on Ca2+/calmodulin-dependent cyclic nucleotide phosphodiestrase activity in rat liver cytosol. Mol Cell Biochem 106: 25–30, 1991
Yamaguchi M, Mori S: Inhibitory effect of calcium-binding protein regucalcin on protein kinase C activity in rat liver cytosol. Biochem Med Metab Biol 43: 140–146, 1990
Yamaguchi M, Sakurai T: Inhibitory effect of calcium-binding protein regucalcin on Ca2+-activated DNA fragmentation in rat liver nuclei. FEBS Lett 279: 281–284, 1991
Yamaguchi M, Kanayama Y: Calcium-binding protein regucalcin inhibits deoxyribonucleic acid synthesis in the nuclei of regenerating rat liver. J Cell Biochem 57: 185–190, 1995
Ueoka S, Yamaguchi M: Inhibitory effect of calcium-binding protein regucalcin on ribonuleic acid synthesis in isolated rat liver nuclei. Mol Cell Biochem 173: 169–175, 1997
Long RM, Moore L: Elevated cytosolic calcium in rat hepatocytes exposed to carbon tetrachloride. J Pharmac Exp Ther 238: 186–191, 1986
Moore L, Davenport GR, Landon EJ: Calcium uptake of a rat liver subcellular fraction in response to in vivo administration of CCl4. J Biol Chem 251: 1197–1201, 1976
Burton A: Study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J 62: 315–323, 1956
Nakamura M, Mori K: Colorimetric determination of inorganic phosphorous in the presence of glucose-1-phosphate and adenosine triphosphate. Nature 182: 1441–1442, 1958
Lowry OH, Rosebrough NJ, Farr AL, Randall FJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–273, 1951
Yamaguchi M, Takei Y, Yamamoto T: Effect of thyrocalcitonin in liver of intact and thyroparathyroidectomized rats. Endocrinology 96: 1004–1008, 1975
Oishi K, Yamaguchi M: Effect of nicotinamide-adenine dinucleotides on Ca2+ transport system in rat liver nuclei: Stimulation of Ca2+ release by NAD+. Mol Cell Biochem 121: 127–133, 1993
Casini AF, Farber JL: Dependence of the CCl4-induced death of cultured hepatocytes on the extracellular calcium concentration. Am J Pathol 105: 138–148, 1981
Kroner H: The intracellular distribution of liver cell calcium in normal rats and one hour after administration of CCl4. Biochem Pharamacol 31: 1069–1073, 1982
Moore L: Inhibition of liver microsomal calcium pump by in vivo administration of CCl4, CHCl3, and 1-DCE. Biochem Pharmacol 29: 2505–2511, 1980
Long RM, Moore L: Cytosolic calcium after carbon tetrachloride, 1, 1-dichloroethylene, and phenylephrine exposure. Studies in rat hepatocytes with phosphorylase a and quin 2. Biochem Pharmacol 36: 1215–1221, 1987
Takahashi H, Yamaguchi M: Activatory effect of regucalcin on hepatic plasma membrane (Ca2+-Mg2+)-ATPase is impaired by liver injury with carbon tetrachloride administration in rats. Mol Cell Biochem 158: 9–16, 1996
Yamaguchi M: Effect of calcium-binding protein regucalcin on Ca2+ transport system in rat liver nuclei: Stimulation of Ca2+ release. Mol Cell Biochem 113: 63–70, 1992
McConky DJ, Nicotera P, Hartzell P, Ballome G, Wyllie AH, Orrenius S: Glucocorticoids activate an endogenous suicide process in thymocytes through the elevation of cytosolic Ca2+ concentration. Arch Biochem Biophys 269: 365–370, 1989
McConky DJ, Harzell D, Duddy SK, Hakansson H, Orrenius S: 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin kills immature thymocytes by Ca2+-mediated endonuclease activation. Science 242: 256–259, 1989
Isogai M, Shimokawa N, Yamaguchi M: Hepatic calcium-binding protein regucalcin is released into the serum of rats administered orally carbon tetrachloride. Mol Cell Biochem 131: 173–179, 1994
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Katsumata, T., Murata, T. & Yamaguchi, M. Alteration in calcium content and Ca2+-ATPase activity in the liver nuclei of rats orally administered carbon tetrachloride. Mol Cell Biochem 185, 153–159 (1998). https://doi.org/10.1023/A:1006803610945
Issue Date:
DOI: https://doi.org/10.1023/A:1006803610945