A sensitive fluorescence-based assay for monitoring GM2 ganglioside hydrolysis in live patient cells and their lysates

Glycobiology

Volumn 20, Issue 3, 2009, Pages 356-365

  Tropak, Michael B ^a   Bukovac, Scott W ^a,b   Rigat, Brigitte A ^a   Yonekawa, Sayuri ^a   Wakarchuk, Warren ^c   Mahuran, Don J ^a,b  

^a HOSPITAL FOR SICK CHILDREN   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c NATIONAL RESEARCH COUNCIL CANADA   (Canada)

Author keywords

AB variant GM2 gangliosidosis; Enzyme enhancement therapy; Pyrimethamine; Sandhoff disease; Tay Sachs disease

Indexed keywords

BETA N ACETYLHEXOSAMINIDASE A; GANGLIOSIDE GM2; LIPOSOME; PYRIMETHAMINE;

ARTICLE; CONTROLLED STUDY; ENZYME KINETICS; ENZYME SPECIFICITY; FIBROBLAST; FLUORESCENCE ANALYSIS; HUMAN; HUMAN CELL; HYDROLYSIS KINETICS; INTERNALIZATION; LYSOSOME; MICHAELIS MENTEN KINETICS; PRIORITY JOURNAL; TAY SACHS DISEASE;

CELLS, CULTURED; FLUORESCENT ANTIBODY TECHNIQUE; G(M2) GANGLIOSIDE; HUMANS; HYDROLYSIS; KINETICS; LIPOSOMES; MASS SPECTROMETRY; TAY-SACHS DISEASE;

EID: 77949886783     PISSN: 09596658     EISSN: 14602423     Source Type: Journal    
DOI: 10.1093/glycob/cwp183     Document Type: Article

References (32)

1. Callahan JW, Pinsky L,Wolfe LS. 1970. GM1-gangliosidosis (Type II): Studies on a fibroblast cell strain. Biochem Med. 4:295-316.
2. Chen B, Rigat B, Curry C, Mahuran DJ. 1999. Structure of the GM2A gene: Identification of an exon 2 nonsense mutation and a naturally occurring transcript with an in-frame deletion of exon 2. Am J Hum Genet. 65:77-87.
3. Folch J, Lees M, Sloane Stanley GH. 1957. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem. 226:497-509.
4. M2 gangliosidoses. In: Scriver CR, Beaudet AL, et al. editors. The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill. p. 2839-2879.
5. Hou Y, Tse R, Mahuran DJ. 1996. The direct determination of the substrate specificity of the (-active site in heterodimeric b-hexosaminidase A. Biochemistry. 35:3963-3969.
6. Jeyakumar M, Butters TD, Dwek RA, Platt FM. 2002. Glycosphingolipid lysosomal storage diseases: Therapy and pathogenesis. Neuropath Appl Neuro. 28:343-357.
7. Kolter T, Sandhoff K. 2005. Principles of lysosomal membrane digestion: Stimulation of sphingolipid degradation by sphingolipid activator proteins and anionic lysosomal lipids. Annu Rev Cell Dev Biol. 21:81-103.
8. Leinekugel P, Michel S, Conzelmann E, Sandhoff K. 1992. Quantitative correlation between the residual activity of beta-hexosaminidase A and arylsulfatase A and the severity of the resulting lysosomal storage disease. Hum Genet. 88:513-523.
9. Lemieux MJ, Mark BL, Cherney MM, Withers SG, Mahuran DJ, James MN. 2006. Crystallographic structure of human beta-hexosaminidaseA: Interpretation of Tay-Sachs mutations and loss of G(M2) Ganglioside Hydrolysis. J Mol Biol. 359:913-929.
10. Maegawa GHB, Tropak M, Butner J, Stockley T, Kok F, Clarke JTR, Mahuran DJ. 2007. Pyrimethamine as a potential pharmacological chaperone for lateonset forms of GM2 gangliosidosis. J Biol Chem. 282:9150-9161.
11. Mahuran DJ. 1999. Biochemical consequences of mutations causing the GM2 Gangliosidoses. Biochim Biophys Acta. 1455:105-138.
12. Mahuran DJ, Lowden JA. 1980. The subunit and polypeptide structure of hexosaminidase from human placenta. Can J Biochem. 58:287-294.
13. Maier T, Strater N, Schuette CG, Klingenstein R, Sandhoff K, Saenger W. 2003. The X-ray crystal structure of human beta-hexosaminidase B provides new insights into Sandhoff disease. J Mol Biol. 328:669-681.
14. Mark BL, Mahuran DJ, Cherney MM, Zhao D, Knapp S, James MN. 2003. Crystal structure of human beta-hexosaminidase B: Understanding the molecular basis of Sandhoff and Tay-Sachs disease. J Mol Biol. 327:1093-1109.
15. Martin DR,RigatBA, Foureman P,Varadarajan GS,HwangM,KrumBK, Smith BF, Callahan JW, Mahuran DJ, Baker HJ. 2008. Molecular consequences of the pathogenic mutation in feline GM1 gangliosidosis. Mol Genet Metab. 94:212-221.
16. Meier EM, Schwarzmann G, F̈urst W, Sandhoff K. 1991. The human GM2 activator protein. A substrate specific cofactor of b-hexosaminidase A. J Biol Chem. 266:1879-1887.
17. Navon R, Kolodny EH, Mitsumoto H, Thomas GH, Proia RL. 1990. Ashkenazi Jewish and non-Jewish adult GM2 gangliosidosis patients share a common genetic defect. Am J Hum Genet. 46:817-821.
18. Novak A, Lowden JA, Gravel YL, Wolfe LS. 1979. Preparation of radiolabeled GM2 and GA2 gangliosides. J Lipid Res. 20:678-681.
19. Phaneuf D, Wakamatsu N, Huang JQ, Borowski A, Peterson AC, Fortunato SR, Ritter G, Igdoura SA, Morales CR, Benoit G, et al. 1996. Dramatically different phenotypes in mouse models of human Tay-Sachs and Sandhoff diseases. Hum Mol Genet. 5:1-14.
20. Schwarzmann G, Sandhoff K. 1987. Lysogangliosides: Synthesis and use in preparing labeled gangliosides. Methods Enzymol. 138:319-341.
21. Sharma R, Bukovac S, Callahan J, Mahuran D. 2003. A single site in human b-hexosaminidase A binds both 6-sulfate-groups on hexosamines and the sialic acid moiety of GM2 ganglioside. Biochim Biophys Acta. 1637:113-118.
22. Sharma R, Deng H, Leung A, Mahuran D. 2001. Identification of the 6-sulfate binding site unique to a-subunit-containing isozymes of human b-hexosaminidase. Biochemistry. 40:5440-5446.
23. Smiljanic-Georgijev N, Rigat B, Xie B, Wang W, Mahuran DJ. 1997. Characterization of the affinity of the GM2 activator protein for glycolipids by a fluorescene dequenching assay. Biochim Biophys Acta. 1339:192-202.
24. Tropak MB, Blanchard J, Withers SG, Brown E, Mahuran D. 2007. Hight-hroughput screening for novel human lysosomal beta-N-acetyl hexosaminidase inhibitors acting as pharmacological chaperones. Chem Biol. 14:153-164.
25. Tropak MB, Kornhaber GJ, Rigat BA, Maegawa GH, Buttner J, Blanchard JE, Murphy C, Tuske SJ, Coales SJ, Hamuro Y, et al. 2008. Identification of pharmacological chaperones for Gaucher disease and characterization of their effects on β-glucocerebrosidase by hydrogen/deuterium exchange mass spectrometry. ChemBioChem. 9:2650-2662.
26. Tropak MB, Mahuran D. 2007. Lending a helping hand, screening chemical libraries for compounds that enhance β-hexosaminidase A activity in GM2 gangliosidosis cells. FEBS J. 274:4951-4961.
27. TropakMB, Reid S, Guiral M,Withers SG, Mahuran DJ. 2004. Pharmacological enhancement of b-hexosaminidase activity in fibroblasts from adult Tay-Sach and Sandhoff patients. J Biol Chem. 279:13478-13487.
28. Tsui ZC, Chen QR, Thomas MJ, SamuelM, Cui Z. 2005. Amethod for profiling gangliosides in animal tissues using electrospray ionization-tandem mass spectrometry. Anal Biochem. 341:251-258.
29. Werth N, Schuette CG, Wilkening G, Lemm T, Sandhoff K. 2001. Degradation of membrane-bound ganglioside GM2 by beta-hexosaminidase A. Stimulation by GM2 activator protein and lysosomal lipids. J Biol Chem. 276:12685-12690.
30. Wright CS, Li SC, Rastinejad F. 2000. Crystal structure of human GM2-activator protein with a novel beta-cup topology. J Mol Biol. 304:411-422.
31. Xie B, McInnes B, Neote K, Lamhonwah A-M, Mahuran D. 1991. Isolation and expression of a full-length cDNA encoding the human GM2 activator protein. Biochem Biophys Res Comm. 177:1217-1223.
32. Zarghooni M, Bukovac S, Tropak M, Callahan J, Mahuran D. 2004. An alpha-subunit loop structure is required for GM2 activator protein binding by beta-hexosaminidase A. Biochem Biophys Res Com. 324:1048-1052.