Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or...
Patent
1997-09-08
1999-11-23
Lankford, Jr., Leon B.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
424 941, 424 946, 435 71, 435 721, 435 8, 435 18, C12Q 100, C12Q 166, C12Q 134
Patent
active
059898038
ABSTRACT:
The present invention provides for a method for treating a subject suffering from a condition associated with an extracellular zinc sphingomyelinase activity which comprises administering to the subject an amount of a zinc sphingmyelinase inhibitor effective to decrease extracellular zinc sphingomyelinase activity in the subject and thereby treat the subject. The present invention also provides for a method for determining whether a compound inhibits an activity of an extracellular zinc sphingomyelinase involving ceramide formation which comprises: (a) contacting a sample containing the zinc sphingomyelinase under acidic pH conditions known to be associated with the activity of such zinc sphingomyelinase, with: (i) a substrate of the zinc sphingomyelinase enzyme, and (ii) the compound being evaluated; (b) measuring the concentration of ceramide in the sample from (a); (c) determining the amount of zinc sphingomyelinase activity in the sample based upon the concentration of ceramide measured in step (b); and (d) comparing the amount of sphingomyelinase activity determined in step (c) with the amount of sphingomyelinase activity determined in the absence of the compound, so as to determine whether the compound inhibits the activity of zinc sphingomyelinase.
REFERENCES:
patent: 4987151 (1991-01-01), Tabas
patent: 5789181 (1998-08-01), Lin et al.
Schissel et al. J. Biol. Chem. vol. 17, pp. 18250-18259, abstract, 1998.
Schissel et al. 69th Scientific Sessions--Am. Heart Assoc., abstract, 1996.
Schissel, S. Dissertation Abstracts Int. vol. 58, No. 9B, abstract, 1997.
Francis, S.H. et al. (1994) Zinc interactions and conserved motifs of the cGMP-binding cGMP-specific phosphodiesterase suggest that it is a zinc hydrolase J. Biol. Chem., 269: 22477-22480 (Exhibit 2).
Hannun, Y. A. and Bell, R. M. (1989) "Functions of sphingolipids and sphingolipid breakdown products in cellular regulation," Science, 243:500-507 (Exhibit 3).
Kolesnick, R. N. (1991) "Sphingomyelin and derivatives as cellular signals," Prog. Lipid Res., 30:1-38 (Exhibit 4).
Levade, T. et al. (1986) "Sphingomyelinases and Niemann-Pick Disease," J. Clin. Chem. Clin. Biochem., 24: 205-220 (Exhibit 5).
Okwu, A. K. et al. (1994) "Regulation of the threshold for lipoprotein-induced acyl-CoA:cholesterol O-acyltransferase stimulation in macrophages by cellular sphingomyelin content," J. Lipid Res., 35(4): 644-655 (Exhibit 6).
Schissel, S. L. et al. (1996) "Zn.sup.2+ -stimulated sphingomyelinase is secreted by many cell types and is a product of the acid sphingomyelinase gene," J. Biol. Chem., 271(31): 18431-18436 (Exhibit 7).
Schissel, S. L. et al. (1996) "Rabbit aorta and human atherosclerotic lesions hydolyze the sphingomyelin of retained low-density lipoprotein: Proposed role for arterial-wall sphingomyelinase in subendothelial retention and aggregation of atherogenic lipoproteins," J. Clin. Invest., 98(6): 1455-1464 (Exhibit 8).
Schuchman, E. H. et al. (1991) "Human acid sphingomyelinase: Isolation, nucleotide sequence, and expression of the full-length and alternatively spliced cDNAs," J. Biol. Chem., 266(13): 8531-8539 (Exhibit 9).
Skiba, P. J. et al. (1996) "The distal pathway of lipoprotein-induced cholesterol esterification, but not sphingomyelinase-induced cholesterol esterification, is energy-dependent," J. Biol. Chem., 271(23): 13392-13400 (Exhibit 10).
Spence, M. W. et al. (1989) "A new Zn.sup.2+ -stimulated sphingomyelinase in fetal bovine serum," J. Biol. Chem., 264(10):5358-5363 (Exhibit 11).
Tabas, I. et al. (1993) "Lipoprotein lipase and sphingomyelinase synergistically enhance the association of atherogenic lipoproteins with smooth muscle cells and extracellular matrix: A possible mechanism for low density lipoprotein and lipoprotein(a) retention and macrophage foam cell formation," J. Biol. Chem., 268(27): 20419-20432 (Exhibit 12).
Williams, K. J. et al. (1992) "Mechanisms by which lipoprotein lipase alters cellular metabolism of lipoprotein(a), low density lipoprotein, and nascent lipoproteins. Roles for low density lipoprotein receptors and heparan sulfate proteoglycans," J. Biol. Chem., 267(19): 13284-13292 (Exhibit 13).
Williams, K. J. and I. Tabas (1995) "The response-to-retention hypothesis of early atherogenesis," Arterioscler. Thromb. Vasc. Biol., 15(5): 551-561 (Exhibit 14).
Xu, X.-X. and I. Tabas (1991) "Sphingomyelinase enhances low density lipoprotein uptake and ability to induce cholesteryl ester accumulation in macrophages," J. Biol. Chem., 266(36): 24849-24858 (Exhibit 15).
Yamamoto, K. (1994) "Microbial Endoglycosidases for Analyses of Oligosaccharide Chains in Glycoproteins," J. Biochem., 116(2): 229-235 (Exhibit 16).
Schissel Scott L.
Tabas Ira
Williams Kevin Jon
Lankford , Jr. Leon B.
Tate Christopher R.
The Trustees of Columbia University in the City of New York
Thomas Jefferson University
White John P.
LandOfFree
Method for treating a subject suffering from a condition associa does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for treating a subject suffering from a condition associa, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for treating a subject suffering from a condition associa will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1220043