Aminoguanidine partially prevents the reduction in liver pyruvate kinase activity in diabetic rats

Amiri Majd, Alimohammad; Goodarzi, Mohammad Taghi; Hassanzadeh, Taghi; Tavilani, Heidar; Karimi, Jamshid

Aminoguanidine partially prevents the reduction in liver pyruvate kinase activity in diabetic rats

Authors

¹ Department of Biochemistry Medical School, Hamadan University of Medical Sciences, 65178 Hamadan, Iran

² Research Center for Molecular Medicine, Hamadan University of Medical Sciences, 65178 Hamadan, Iran

Abstract

Background : Low molecular weight aldehydes and carbonyl compounds which are derived from glucose metabolism are prevalent in diabetic plasma. These compounds react to amino groups of Lys and Arg and lead to the formation of advanced glycation end products (AGEs). This modification changes the function of the proteins. The present study aimed to survey the effect of diabetes on rat liver pyruvate kinase activity and to show the inhibitory effect of aminoguanidine (AG).
Materials and Methods : Male Wistar rats (n = 18, 6 to 8 weeks old) were divided randomly in three groups: the first group as control; second and third groups were induced diabetes using streptozocin. Third group received AG orally for 8 weeks after diabetes induction. Liver cell homogenate was prepared from all studied groups and L-type pyruvate kinase was separated from the homogenate. Pyruvate kinase activity was determined in both liver cell homogenate and extracted L-type PK. The PK activity was compared in all samples between groups.
Results : PK activity in isolated form and in liver cell homogenate was lower in diabetic rats as compared to control group. AG-treated group showed higher PK activity compared to untreated diabetic group; however, the difference was not significant. Non-significant difference in PK activity between AG-treated diabetic and non-diabetic (control) group indicated the inhibitory effect of AG in glycation of PK.
Conclusion : The obtained results showed PK activity decreased in diabetic rats and AG can partially prevent the reduction in PK activity.

Keywords

References

1.	Eaton JW, Dean RT. Diabetes and atherosclerosis. In: Dean RT, Kelly DT, editors. Atherosclerosis. Oxford: Oxford University Press; 2000.
2.	Striban A, Gawlowski T, Roden M. Vascular effect of advanced glycation end products: Clinical effect and molecular mechanisms. Molecular Metabolism 2014;3:94-108.
3.	Kaul K, Tarr JM, Ahmad SI, Kohner EM, Chibber R. Introduction to diabetes mellitus. Adv Exp Med Biol 2012;771:1-11
4.	Wells-Knecht KJ, Zyzak DV, Litchfield JE, Thorpe SR, Baynes JW. Mechanism of autoxidative glycosylation: Identification of glyoxal and arabinose as intermediates in autoxidative modification of proteins by glucose. Biochemistry 1995;34:3702-9.
5.	Thornalley PJ, Langborg A, Minhas HS. Formation of glyoxal, methylglyoxal and 3-deoxyglucosone in the glycation of proteins by glucose. Biochem J 1999;344:109-16.
6.	Phillips SA, Thornalley PJ. The formation of methylglyoxal from triose phosphates. Investigation using a specific assay for methylglyoxal. Eur J Biochem 1993;212:101-5.
7.	Thornalley PJ. Pharmacology of methylglyoxal: Formation, modification of proteins and nucleic acids and enzymatic detoxification-A role in pathogenesis and antiproliferative chemotherapy. Gen Pharmacol 1996;27:565-73.
8.	Anderson MM, Hazen SL, Hsu FF, Heinecke JW. Human neutrophils employ the myeloperoxidase-hydrogen peroxide-chloride system to convert hydroxy-amino acids into glycolaldehyde, 2-hydroxypropanal, and acrolein. A mechanism for the generation of highly reactive alpha-hydroxy and alpha, beta-unsaturated aldehydes by phagocytes at sites of inflammation. J Clin Invest 1997;99:424-32.
9.	Lo TW, Westwood ME, McLellan AC, Selwood T, Thornalley PJ. Binding and modification of proteins by methylglyoxal under physiological conditions: A kinetic and mechanistic study with N- acetylarginine, N-acetyl-lysine, and bovine serum albumin. J Biol Chem 1994;269:32299-305.
10.	Frye EB, Degenhardt TP, Thorpe SR, Baynes JW. Role of the Maillard Reaction in Aging of Tissue Proteins: Advanced glycation end product-dependent increase in imidazolium cross-links in human lens proteins. J Biol Chem 1998;273:18714-9.
11.	Thornalley PJ. Use of aminoguanidine (Pimagedine) to prevent the formation of advanced glycation end products. Arch Biochem Biophys 2003;419:31-40.
12.	Brownlee M, Vlassara H, Kooney A, Ulrich P, Cerami A. Aminoguanidine prevents diabetes-induced arterial wall protein cross-linking. Science 1986;232:1629-32.
13.	Vasan S, Foiles P, Founds H. Therapeutic potential of breakers of advanced glycation end product-protein crosslinks. Arch Biochem Biophys 2003;419:89-96.
14.	Cameron NE, Cotter MA. Rapid reversal by aminoguanidine of the neurovascular effects of diabetes in rats: Modulation by nitric oxide synthase inhibition. Metabolism 1996;45:1147-52.
15.	Berg JM, Tymoczko JL, Stryer L. Protein Turnover and amino acid catabolism. Biochemistry. 5 ^th ed. New York: WH Freeman Publisher; 2002.
16.	Munoz E, Ponce E. Pyruvate kinase: Current status of regulatory and functional properties. Comp Biochem Physiol B Biochem Mol Biol 2003;135:197-218.
17.	Muirhead H, Clayden DA, Barford D, Lorimer CG, Fothergill-Gilmore LA, Schiltz E, et al. The structure of cat muscle pyruvate kinase. EMBO J 1986;5:475-81.
18.	Jurica MS, Mesecar A, Heath PJ, Shi W, Nowak T, Stoddard BL. The Allosteric Regulation of pyruvate kinase by fructose-1,6-bisphosphate. Structure 1998;6:195-210.
19.	Valentini G, Chiarelli LR, Fortin R, Dolzan M, Galizzi A, Abraham DJ, et al. Structure and function of human erythrocyte pyruvate kinase. J Biol Chem 2002;277:23807-14.
20.	Takahashi K. The reaction of phenylglyoxal with arginine residues in proteins. J Biol Chem 1968;243:6171-9.
21.	Seidler NW, Kowalewski C. Methylglyoxal-induced glycation affects protein topography. Arch Biochem Biophys 2003;410:149-54.
22.	Kang JH. Modification and inactivation of human Cu, Znsuperoxide dismutase by methylglyoxal. Mol Cells 2003;15:194-9.
23.	Halder J, Ray M, Ray S. Inhibition of glycolysis and mitochondrial respiration of Ehrlich ascites carcinoma cells by methylglyoxal. Int J Cancer 1993;54:443-9.
24.	Biswas S, Ray M, Misra S, Dutta DP, Ray S. Selective inhibition of mitochondrial respiration and glycolysis in human leukaemic leucocytes by methylglyoxal. Biochem J 1997;323:343-8.
25.	Lee HJ, Howell SK, Sanford RJ, Beisswenger PJ. Methylglyoxal can modify GAPDH activity and structure. Ann N Y Acad Sci 2005;1043:135-45.
26.	Morgan PE, Dean RT, Davies MJ. Inactivation of cellular enzymes by carbonyl and protein-bound glycation/glycoxidation products. Arch Biochem Biophys 2002;403:259-69.
27.	Iori E, Millioni R, Puricelli L, Arrigoni G, Lenzini L, Trevisan R, et al. Glycolytic enzyme expression and pyruvate kinase activity in cultured fibroblasts from type 1 diabetic patients with and without nephropathy. Biochim Biophys Acta 2008;1782:627-33.
28.	Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248-54.
29.	Petersen EA, Sober HA. Column chromatography of proteins: Substituted Celluloses. Methods Enzymol 1962;5:3-27.
30.	Farina FA, Shatton JB, Morris HP, Weinhouse S. Isozymes of Pyruvate Kinase in Liver and Hepatomas of the Rat. Cancer Res 1974;34:1439-46.
31.	Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophageT4. Nature 1970;227:680-5.
32.	Brownlee M, Vlassara H, Cerami A. Nonenzymatic glycosylation and the pathogenesis of diabetic complications. Ann Intern Med 1984;101:527-37.
33.	Stoppa GR, Cesquini M, Roman EA, Ogo SH, Torsoni MA. Aminoguanidine prevented impairment of blood antioxidant system in insulin-dependent diabetic rats. Life Sci 2006;78:1352-61.
34.	Elgawish A, Glomb M, Friedlander M, Monnier VM. Involvement of hydrogen peroxide in collagen cross-linking by glucose in vitro and in vivo. J Biol Chem 1996;271:12964-71.
35.	Davison GW, George L, Jackson SK, Young IS, Davies B, Bailey DM, et al. Exercise, free radicals, and lipid peroxidation in type 1 diabetes mellitus. Free Radic Biol Med 2002;33:1543-51.
36.	Parks WC, Drake RL. Insulin mediates the stimulation of pyruvate kinase by a dual mechanism. Biochem J 1982;208:333-7.
37.	Belfiore F, Rabuazzo AM, Napoli E, Borzi V, Vecchio L. Enzymes of glucose metabolism and of the citrate cleavage pathway in adipose tissue of normal and diabetic subjects. Diabetes 1975;24:865-73.
38.	Lupi R, Marselli L, Dionisi S, Del Guerra S, Boggi U, Del Chiaro M, et al. Improved insulin secretory function and reduced chemotactic properties after tissue culture of islets from type 1 diabetic patients. Diabetes Metab Res Rev 2004;20:246-51.
39.	Kondoh Y, Kawase M, Kawakami Y, Ohmori S. Concentrations of D-lactate and its related metabolic intermediates in liver, blood, and muscle of diabetic and starved rats. Res Exp Med (Berl) 1992;192:407-14.
40.	Diamant YZ, Shafrir E. Placental enzymes of glycolysis, gluconeogenesis and lipogenesis in the diabetic rat and in starvation. Comparison with maternal and foetal liver. Diabetologia 1978;15:481-5.
41.	Rossi I, Sanchez-Arias JA, Feliu JE. Effect of streptozotocin diabetes on the glycolytic flux and on fructose 2, 6-bisphosphate levels in isolated rat enterocytes. Metabolism 1990;39:882-5.
42.	Thomas MC, Tikellis C, Kantharidis P, Burns WC, Cooper ME, Forbes JM. The role of advanced glycation in reduced organic cation transport associated with experimental diabetes. J Pharmacol Exp Ther 2004;311:456-66.
43.	Kazachkov M, Chen K, Babiy S, Yu PH. Evidence for in Vivo Scavenging by Aminoguanidine of Formaldehyde Produced via Semicarbazide-Sensitive Amine Oxidase-Mediated Deamination. J Pharmacol Exp Ther 2007;322:1201-7.
44.	Limaye PV, Raghuram N, Sivakami S. Oxidative stress and gene expression of antioxidant enzymes in the renal cortex of streptozotocin-induced diabetic rats. Mol Cell Biochem 2003;243:147-52.
45.	Giardine I, Fard AK, Hatchell DL, Brownlee M. Aminoguanidine inhibits reactive oxygen species formation, lipid peroxidation, and oxidant induced apoptosis. Diabetes 1998;47:1114-20.

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