Human neuroblastoma cells transfected with two Chinese presenilin 1 mutations are sensitized to trophic factor withdrawal and protected by insulin-like growth factor-1.
BACKGROUND
Two novel presenilin 1 (PS1) mutations, V97L and A136G, were recently found to be involved in the early-onset of Alzheimer's disease in two Chinese families. This research aimed to verify their pathological effects.


METHODS
The human neuroblastoma SH-SY5Y cells stably transfected with these two Chinese presenilin 1 mutations were established to explore whether they are sensitive to, or influenced by, serum deprivation and protected by insulin-like growth factor-1 (IGF-1). Apoptosis rate, glucose uptake of the cells and the expression of glucose transport protein 1 (GLUT1) on cell membranes were examined.


RESULTS
The V97L or A136G mutants significantly decreased the cells viability and increased the apoptosis rate when compare to PS1wt and mock transfected cells. IGF-1 was found to improve the viability of these two kinds of mutant cells significantly, and to show a protective effect for the mutants when they were treated with trophic deprivation. The glucose uptake of each transfected cell line increased to about 25% after IGF-1 treatment, GLUT1 expression on the cell membrane increased modestly by about 15% - 20%.


CONCLUSIONS
Enhanced sensitivity to trophic withdrawal in the cells transfected with the two Chinese PS1 mutations may contribute to the neuron apoptosis. IGF-1 provided a protective effect to cells, possibly through an enhanced glucose transport and mitochondrial activities.
Fang
Bo-yan
BY
Department of Neurology, First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, China.
Jia
Jian-ping
JP
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D044466:Asian People / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002681:China; D005434:Flow Cytometry; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009154:Mutation; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053764:Presenilin-1 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
D051272:Glucose Transporter Type 1; D053764:Presenilin-1; C495677:SLC2A1 protein, human; D007334:Insulin-Like Growth Factor I; D005947:Glucose