Determination of the content of Gd3+ in gadoteric acid meglumine salt injection by ICP-MS method / 药学实践杂志

Objective To establish a method for determining the content of Gd3+ in gadoteric acid meglumine salt injection. Methods ICP-MS was used. The separation column was a metal chelate column (1-ml Chelating Sepharose column), column temperature was normal temperature. Flow rate was 1 ml/min. Injection volume was 500 μl. Atoms were measured by ICP-MS with a molecular weight of 157 (The molecular weight of Gd was 157). The carrier gas was argon. Results The linear range of Gd3+ mass concentration was 0-500 ng/ml (r=1.000); The precision, stability and repeatability of the sample recovery test were all in accordance with the requirements. Conclusion The method was simple in operation, accurate in results and good in repeatability, which could be used to determine the content of Gd3+ in gadoteric acid meglumine salt injection.

Ganglioside GD3 synthase (GD3S), a novel cancer drug target

Gangliosides are a class of important glycosphingolipids containing sialic acid that are widely distributed on the outer surface of cells and are abundantly distributed in brain tissue. Disialoganglioside with three glycosyl groups (GD3) and disialoganglioside with two glycosyl groups (GD2) are markedly increased in pathological conditions such as cancers and neurodegenerative diseases. GD3 and GD2 were found to play important roles in cancers by mediating cell proliferation, migration, invasion, adhesion, angiogenesis and in preventing immunosuppression of tumors. GD3 synthase (GD3S) is the regulatory enzyme of GD3 and GD2 synthesis, and is important in tumorigenesis and the development of cancers. The study of GD3S as a drug target may be of great significance for the discovery of new drugs for cancer treatment. This review will describe the gangliosides and their roles in physiological and pathological conditions; the roles of GD3 and GD2 in cancers; the expression, functions and mechanisms of GD3S, and its potential as a drug target in cancers.

GD3 Accumulation in Cell Surface Lipid Rafts Prior to Mitochondrial Targeting Contributes to Amyloid-beta-induced Apoptosis

Neuronal apoptosis induced by amyloid beta-peptide (A beta) plays an important role in the pathophysiology of Alzheimer's disease (AD). However, the molecular mechanism underlying A beta-induced apoptosis remains undetermined. The disialoganglioside GD3 involves ceramide-, Fas- and TNF-alpha-mediated apoptosis in lymphoid cells and hepatocytes. Although the implication of GD3 has been suggested, the precise role of GD3 in A beta-induced apoptosis is still unclear. Here, we investsigated the changes of GD3 metabolism and characterized the distribution and trafficking of GD3 during A beta-induced apoptosis using human brain-derived TE671 cells. Extracellular A beta induced apoptosis in a mitochondrial-dependent manner. GD3 level was negligible in the basal condition. However, in response to extracellular A beta, both the expression of GD3 synthase mRNA and the intracellular GD3 level were dramatically increased. Neosynthesized GD3 rapidly accumulated in cell surface lipid microdomains, and was then translocated to mitochondria to execute the apoptosis. Disruption of membrane lipid microdomains with methyl-beta-cyclodextrin significantly prevented both GD3 accumulation in cell surface and A beta-induced apoptosis. Our data suggest that rapidly accumulated GD3 in plasma membrane lipid microdomains prior to mitochondrial translocation is one of the key events in A beta-induced apoptosis.