Preferences help
enabled [disable] Abstract
Number of results
2012 | 59 | 4 | 489-493
Article title

Role of heat-shock proteins and cobalamine in maintaining methionine synthase activity

Title variants
Languages of publication
Atheromatous plaque is one of the most common cardiovascular-related diseases. Reports show a connection between its development and the levels of homocysteine. In pathological states high levels of homocysteine in the organism can be caused by the malfunction of the methionine synthase pathway. Bacterial methionine synthase (MetH) is a homologue of the human methionine syntase (MS). In this study we aimed to investigate the functional relations between MetH and its cofactor - cobalamine - under stress conditions. We have demonstrated that heat shock proteins (Hsp 70/100 system or HtpG) can protect MetH activity under stress conditions. Moreover, in the presence of cobalamine they can restore the activity of partially denatured methionine synthase.
Physical description
  • Department of Molecular and Cellular Biology, Intercollegiate Faculty of Biotechnology University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland
  • Department of Biotechnology, Intercollegiate Faculty of Biotechnology University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland
  • Department of Microbiology, University of Szczecin, Szczecin, Poland
  • Department of Molecular Biology, University of Gdańsk, Gdańsk, Poland
  • Department of Molecular and Cellular Biology, Intercollegiate Faculty of Biotechnology University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland
  • Department of Neurology, Medical University of Gdańsk, Gdańsk, Poland
  • Department of Molecular and Cellular Biology, Intercollegiate Faculty of Biotechnology University of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland
  • Amaratunga M, Fluhr K, Jarrett J, Drennan K, Ludwig M, Matthews R, Scholten J (1996) A synthetic module for the metH gene permits facile mutagenesis of the cobalamin-binding region of Escherichia coli methionine synthase: initial characterization of seven mutant proteins. Biochemistry 35: 2453-2463.
  • Austin RC, Lentz SR, Werstuck GH (2004) Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease. Cell Death Differ 11: 56-64.
  • Banecki B, Zylicz M (1996) Real time kinetics of the DnaK/DnaJ/GrpE molecular chaperone machine action. J Biol Chem 271: 6137-6143.
  • Bellamy MF, McDowell IF, Ramsey MW, Brownlee M, Bones C, Newcombe RG, Lewis MJ (1998) Hyperhomocysteinemia after an oral methionine load acutely impairs endothelial function in healthy adults. Circulation 98: 1848-1852.
  • Berberian P, Myers W, Tytell M, Challa V, Bond M (1990) Immunohistochemical localization of heat shock protein-70 in normal-appearing and atherosclerotic specimens of human arteries. Am J Pathol 136: 71-80.
  • Chambers JC, McGregor A, Jean-Marie J, Kooner JS (1998) Acute hyperhomocysteinaemia and endothelial dysfunction. Lancet 351: 36-7.
  • Chanarin I, Deacon R, Lumb M, Perry J (1992) Cobalamin and folate: recent developments. J Clin Path 45: 277-283.
  • Dayal S, Bottiglieri T, Arning E, Maeda N, Malinow MR, Sigmund CD, Heistad DD, Faraci FM, Lentz SR (2001) Endothelial dysfunction and elevation of S-adenosylhomocysteine in cystathionine β-synthasedeficient mice. Circ Res 88: 1203-1209.
  • Drummond JT, Jarrett J, González J C, Huang S, Matthews RG (1995) Characterization of nonradioactive assays for cobalamin-dependent and cobalaminindependent methionine synthase enzymes. Anal Biochem 228: 323-329.
  • Eberhardt RT, Forgione MA, Cap A, Leopold JA, Rudd MA, Trolliet M, Heydrick S, Stark R, Klings ES, Moldovan NI, Yaghoubi M, Goldschmidt-Clermont PJ, Farber HW, Cohen R, Loscalzo J (2000) Endothelial dysfunction in a murine model of mild hyperhomocyst(e)inemia. J Clin Invest 106: 483-491.
  • Finkelstein JD, Martin JJ (1986) Methionine metabolism in mammals. Adaptation to methionine excess. J Biol Chem 261: 1582-1587.
  • Genest O, Hoskins J, Camberg J, Doyle A, Wickner S (2011) Heat shock protein 90 from Escherichia coli collaborates with the DnaK chaperone system in client protein remodeling. Proc Natl Acad Sci USA 108: 8206
  • Georgopoulos C, Welch WJ (1993) Role of the major heat shock proteins as molecular chaperones. Annu Rev Cell Biol 9: 601-634.
  • Guenther BD, Sheppard CA, Tran P, Rozen R, Matthews RG, Ludwig ML (1999) The structure and properties of methylenetetrahydrofolate reductase from Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia. Nat Struct Biol 6: 359-365.
  • Hartl FU (1996) Molecular chaperones in cellular protein folding. Nature 381: 571-580.
  • Hofmann MA, Lalla E, Lu Y, Gleason MR, Wolf BM, Tanji N, Ferran LJ Jr, Kohl B, Rao V, Kisiel W, Stern DM, Schmidt AM (2001) Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model. J Clin Invest 107: 675-683.
  • Jakóbkiewicz-Banecka J, Kloska A, Stepnowska M, Banecki B, Węgrzyn A, Wegrzyn G (2005) A bacterial model for studying effects of human mutations in vivo: Escherichia coli strains mimicking a common polymorphism in the human MTHFR gene. Mutation Res 578: 175-186.
  • Kanani PM, Sinkey CA, Browning RL, Allaman M, Knapp HR, Haynes WG (1999) Role of oxidant stress in endothelial dysfunction produced by experimental hyperhomocyst(e)inemia in humans. Circulation 100: 1161-1168.
  • Lentz SR, Sobey CG, Piegors DJ, Bhopatkar MY, Faraci FM, Malinow MR, Heistad DD (1996) Vascular dysfunction in monkeys with diet-induced hyperhomocyst(e)inemia. J Clin Invest 98: 24-29.
  • Lentz SR, Erger RA, Dayal S, Maeda N, Malinow MR, Heistad DD, Faraci FM (2000) Folate dependence of hyperhomocysteinemia and endothelial dysfunction in cystathionine β-synthase-deficient mice. Am J Physiol Heart Circ Physiol 279: 970-975.
  • Madrigal-Matute J, López-Franco O, Blanco-Colio LM, Muñoz-García B, Ramos-Mozo P, Ortega L, Egido J, Martín-Ventura JL (2010) Heat shock protein 90 inhibitors attenuate inflammatory responses in atherosclerosis. Cardiovasc Res 86: 330-337.
  • McCully K (2005) Hyperhomocysteinemia and arteriosclerosis: historical perspectives. Clin Chem Lab Med 43: 980-986.
  • Quéré I, Hillaire-Buys D, Brunschwig C, Chapal J, Janbon C, Blayac J, Petit P, Loubatières-Mariani M (1997) Effects of homocysteine on acetylcholine- and adenosine-induced vasodilatation of pancreatic vascular bed in rats. Br J Pharmacol 122: 351-357.
  • Rosenblatt DS, Fenton WA (2001) Inherited disorders of folate and cobalamin transport and metabolism. In The Metabolic and Molecular Basies of Inherited Disease. Scriver CR, Beaudet Al, Sly WS, Valle D, eds, pp 3897-3933. McGraw-Hill, New York.
  • Sawuła W, Banecka-Majkutewicz Z, Kadziński L, Jakóbkiewicz-Banecka J, Wegrzyn G, Nyka W, Banecki B (2008) Improved HPLC method for total plasma homocysteine detection and quantification. Acta Biochim Pol 55: 119-125.
  • Sawuła W, Banecka-Majkutewicz Z, Kadziński L, Jakóbkiewicz-Banecka J, Wegrzyn G, Nyka W, Banecki B (2009) Homocysteine level and metabolism in ischemic stroke in the population of Northern Poland. Clin Biochem 42: 442-447.
  • Spence J, Georgopoulos C (1989) Purification and properties of the Escherichia coli heat shock protein, HtpG. J Biol Chem 264: 4398-4403.
  • Toole JF, Malinow MR, Chambless LE, Spence JD, Pettigrew LC, Howard VJ, Sides EG, Wang CH, Stampfer M (2004) Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. J Am Med Ass 291: 565-75.
  • Ungvari Z, Pacher P, Rischak K, Szollar L, Koller A (1999) Dysfunction of nitric oxide mediation in isolated rat arterioles with methionine dietinduced hyperhomocysteinemia. Arterioscl Thromb Vasc Biol 19: 1899-1904.
  • Wawrzynów A, Banecki B, Wall D, Liberek K, Georgopoulos C, Zylicz M (1995) ATP hydrolysis is required for the DnaJ-dependent activation of DnaK chaperone for binding to both native and denatured protein substrates. J Biol Chem 270: 19307-19311.
  • Wilcken DE, Wilcken B (1976) The pathogenesis of coronary artery disease. A possible role for methionine metabolism. J Clin Invest 57: 1079-1082.
  • Woo KM, Kim KI, Goldberg AL, Ha DB, Chung CH (1992) The heat-shock protein ClpB in Escherichia coli is a protein-activated ATPase. J Biol Chem 267: 20429-20434.
  • Xu Q (2002) Role of heat shock proteins in atherosclerosis. Arterioscler Thromb Vasc Biol 22: 1547-1559.
  • Żylicz M, Ang D, Georgopoulos C (1987) The grpE protein of Escherichia coli. Purification and properties. J Biol Chem 262: 17437-17442.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.