Human neuroblastoma cells transfected with two Chinese presenilin 1 mutations are sensitized to trophic factor withdrawal and protected by insulin-like growth factor-1.
Chin Med J (Engl)
; 121(10): 910-5, 2008 May 20.
Article
em En
| MEDLINE
| ID: mdl-18706205
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Insulin-Like I
/
Apoptose
/
Presenilina-1
/
Mutação
Limite:
Humans
País/Região como assunto:
Asia
Idioma:
En
Revista:
Chin Med J (Engl)
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
China