Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five glycosphingolipids (GSL), glucosylceramide, lactosylceramide, trihexosylceramide, globoside, and hematoside (GM3) were studied in serum from normal human subjects and patients with dyslipoproteinemia and found to be exclusively associated with the various classes of serum lipoproteins. Based on a unit weight of lipoprotein protein, the total amount of GSL in serum normal subjects was twice as high in very low density lipoprotein (VLDL) (d less than 1.006 g/ml) and low density lipoprotein (LDL) (d 1.019-1.063 g/ml) as in high density lipoproteins HDL2 (d 1.063-1.125 g/ml) or HDL3 (d 1.125-1.21 g/ml). In abetalipoproteinemia the levels of serum GSL were slightly reduced when compared to normal serum and were all found in the only existing lipoprotein, HDL; this contained 2-3 moles of GSL/ mole of lipoprotein as compared to 0.5 GSL/mole in normal HDL. In hypobetalipoproteinemia and Tangier disease, the serum glycosphingolipids were 10 to 30% reduced in concentration compared to the 75% reduction in other lipids, and were again found to be associated only with the serum lipoproteins. The relative proportions of GSL did not vary substantially in the normo- and hypolipidemic subjects studied. Only in patients with homozygous familial hypercholesterolemia was there a significant (3-4-fold) elevation of all of the five GSL species and this elevation of all of the five GSL species and this elevation correlated well with that of the circulating cholesterol and LDL. On a molar basis the LDL of these patients contained the same amount of GSL as normal subjects (5 moles GSL/mole protein). It is concluded that: (1) glycosphingolipids are associated only with the major lipoprotein classes in both normal and dyslipoproteinemic serum; (2) the relative proportions of the five glycosphingolipids are not significantly affected by dyslipoproteinemia; (3) only in severe hypolipoproteinemia do the remaining serum lipoproteins carry a complement of glycosphingolipids greater than normal. Although our results establish that glycosphingolipids are intimately associated with serum lipoproteins, the mode of association or the structural and functional significance of such an association remains undetermined.
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PMID:Distribution of glycosphingolipids in the serum lipoproteins of normal human subjects and patients with hypo- and hyperlipidemias. 17 13

The effects of stanozolol, 17-methyl-2H-5 alpha-androst-2-eno [3,2-c] pyrazol-17 beta-ol, on lipoprotein levels were assessed in a short-term (6 wk) prospective study of 10 normolipidemic, postmenopausal, osteoporotic women. While total cholesterol and triglyceride levels remained constant, equal and offsetting responses were seen in low density lipoprotein (LDL) cholesterol (+30.9 +/- 28.1 mg/dl [mean +/- S.D.], p less than 0.01, a 21% increase) and high density lipoprotein (HDL) cholesterol (-32.5 +/- 11.9 mg/dl [mean +/- S.D.], p less than 0.001, a 53% decline). Hence the LDL/HDL ratio increased dramatically, from 2.5 +/- 0.7 to 6.8 +/- 2.5. Within HDL, stanozolol was associated with a greater decline in HDL2 (from 26.0 +/- 7.4 mg/dl to 3.8 +/- 1.9 mg/dl, p less than 0.001, an 85% decrease) than HDL3 (which diminished from 35.7 +/- 3.2 to 24.1 +/- 5.8 mg/dl. p less than 0.001, a 35% decrease). The major HLD apolipoproteins also declined (A-I by a mean of 41% and A-II by 24%, both p less than 0.001). Postheparin hepatic triglyceride lipase increased (off treatment 74 +/- 42 nmole free fatty acid min-1 mole-1, on treatment 242 +/- 110, n = 6, p = 0.06). All changes were reversed by 5 wk following termination of the drug. These lipoprotein changes suggest caution in the long term prescription of stanozolol, particularly in those without overriding clinical indications for its use.
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PMID:Reduction in high density lipoproteins by anabolic steroid (stanozolol) therapy for postmenopausal osteoporosis. 681 37

Human carriers of apolipoprotein A-I(Milano) (Arg173 --> Cys substitution in apolipoprotein A-I) are characterized by an HDL deficiency in which small, dense HDL accumulate in plasma. Because affected individuals are heterozygous for this mutation, the full impact of apolipoprotein A-I(Milano) (apoA-I(Milano)) on HDL-cholesterol metabolism is unknown. In this study, apoA-I(Milano) transgenic mice were used to evaluate the extent of apoA-I(Milano) dimerization and HDL particle size restriction in the absence of wild-type apoA-I. Murine apoA-I knockout mice were utilized to express apoA-I(Milano) and human apoA-II in the presence of wild-type, human apoA-I (apoA-IMilano/A-Iwt/A-II) and in its absence (apoA-IMilano/A-II). Plasma HDL-cholesterol concentrations were similar (30 mg/dl) in both lines of apoA-I(Milano) transgenic mice. In the apoA-IMilano/A-Iwt/A-II phenotype, 14% of the apoA-I(Milano) formed homodimers and 33% formed heterodimers with apoA-II. ApoA-I(Milano) homodimers increased by 71% in the apoA-IMilano/A-II transgenics and was associated with an abundance of small, 7.6-nm HDL3-sized particles compared to the 9.5, 8.3, and 7.6-nm-sized particles in apoA-IMilano/A-Iwt/A-II mice. The unesterified cholesterol/cholesteryl ester mole ratio of HDL was elevated by 45% in apoA-IMilano/A-Iwt/A-II mice and by 90% in apoA-IMilano/A-II transgenics compared to wild-type (human apoA-I/A-II). Both apoA-I(Milano) transgenics possessed normal levels of plasma LCAT activity, but endogenous cholesterol esterification rates were reduced by 50% compared to controls. Thus, HDL particle size restriction was not the result of impaired LCAT activation; rather, dimerization of apoA-I(Milano) limited the esterification of cholesterol on endogenous HDL. In the absence of wild-type apoA-I, the more extensive dimerization of apoA-I(Milano) severely limited cholesteryl ester accumulation on plasma HDL accounting for the abundance of small, 7.6-nm HDL3 particles in apoA-IMilano/A-II mice.
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PMID:High density lipoprotein particle size restriction in apolipoprotein A-I(Milano) transgenic mice. 939 29

Turbidity (absorbance at 470 nm) measurements revealed human serum low density lipoprotein (LDL) to cause, within a few minutes and at physiological pH and [NaCl], the aggregation of liquid crystalline large unilamellar liposomes (LUVs) of dimyristoylphosphatidylglycerol (DMPG). No evidence for concomitant lipid or aqueous contents mixing was obtained with fluorescent assays for these processes, in keeping with the lack of fusion of LUVs. Involvement of apoB is implicated by the finding that tryptic digestion of LDL abrogates its ability to cause aggregation. Aggregation is not caused by VLDL, HDL2, or HDL3. Interestingly, also oxidised LDL failed to aggregate DMPG vesicles. Aggregation of DMPG LUVs by LDL did depend on the ionic strength of the medium as well as on the phase state of the lipid. More specifically, below the main transition temperature Tm maximal aggregation was seen in the presence of 25-100 mM NaCl, whereas slightly higher (up to 150 mM) [NaCl] were required when T>Tm. Aggregation due to LDL was also observed for dimyristoylphosphatidylserine as well as for dipalmitoylphosphatidylglycerol LUVs, whereas liposomes composed of either unsaturated acidic phospholipids or different phosphatidylcholines were not aggregated. Involvement of electrostatic attraction between the acidic phosphate of DMPG and cationic residues in apoB is suggested by the finding that increasing the content of dimyristoylphosphatidylcholine (DMPC) in DMPG liposomes reduced their aggregation and at XDMPC=0.50 no response was evident. Notably, increasing the mole fraction of 1-palmitoyl-2-oleyl-PG (POPG) in DMPG LUVs progressively reduced their aggregation by LDL and at XPOPG=0.50 there was complete inhibition. The latter effect of POPG is likely to be due to augmented hydration of the unsaturated lipid constituting a barrier for the contact between apoB and the vesicle surface. In keeping with this view, the presence of the strongly hygroscopic polymer, poly(ethylene glycol) at 1% (by weight) enhanced the aggregation and could partly reverse the inhibition by POPG.
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PMID:Aggregation of dimyristoylphosphatidylglycerol liposomes by human plasma low density lipoprotein. 973 56