NATURAL AND SYNTHETIC GANGLIOSIDES AMELIORATE CALCIUM-INDUCED CYTOTOXICITY

Alex Bisignano, Aimee Gasior, Anmol Gupta, Tatiana Lau, Jennifer Lin, Keithe Saclayan, Joran Sequeira, Ken Shen, Tripta Singh, Swarup Swaminathan, Kathy Zhang

Advisor: Dr. Diane F. Kozireski-Chuback
Assistant: Carl W.F. Bird

ABSTRACT

Apoptosis, or cell death, occurs as a result of calcium influx in the neuronal cell. To prevent cell apoptosis, one must control the entrance and exit of calcium ions. This study was conducted to compare the ability of two different compounds, LIGA-20 and GM1, to control calcium ion levels within two neuroblastoma cells, NG108 and NG-CR72. While the NG108 cell line contains the naturally occurring GM1 ganglioside, this compound is absent from the mutant NG-CR72 cells. However, NG108 cells have properties more similar to the neurons found in the brain. Different types of cells were used in order to determine whether an unnatural amount of GM1 ganglioside affects control of calcium ion levels. Intracellular calcium ion levels were observed by staining the cells with fluo-4 dye and observing the intensity of the resulting florescence. LIGA-20 was found to have better control over the calcium-ion level within both NG108 and NG-CR72 cells. This can be attributed to the smaller size of LIGA-20, a property that enables this ganglioside to pass through the plasma membrane and insert itself into the nuclear membrane. In effect, LIGA-20 provides a second line of defense from the influx of calcium ions. Also, the smaller size of LIGA-20 enables it to quickly travel through the plasma membrane. This results in a shorter time for LIGA-20 to attach itself to the nuclear membrane and could be the difference between cell survival and apoptosis. Finally, unnaturally increased levels of GM1 had a negative effect on NG108 cells; the calcium ion level increased when only GM1 was added to the cell culture. The results of the study therefore suggest that LIGA-20 is a more effective controller of intracellular calcium ion levels.

Team 8