Androgen induced cell death in SHSY5Y neuroblastoma cells expressing wild-type and spinal bulbar muscular atrophy mutant androgen receptors.
Spinal bulbar muscular atrophy (SBMA) is one of a family of inherited neurodegenerative diseases caused by expansion of CAG encoding polyglutamine repeats; in SBMA the affected gene is the androgen receptor. To understand further the mechanisms that lead to neuronal cell death in SBMA, we generated SHSY5Y neuroblastoma cell lines that stably express identical levels of wild-type (19 polyglutamine repeat) or SBMA (52 polyglutamine repeat) androgen receptor. Parental SHSY5Y cells do not express detectable levels of the androgen receptor. In the absence of androgen, the transfected cell lines have similar phenotypes and growth characteristics to parental SHSY5Y cells. However, upon treatment with androgen, both cell lines undergo a marked dose-dependent loss of viability; this loss was significantly greater in cells expressing the SBMA receptor. Morphological analyses of the androgen treated cells revealed that cell death bore hallmarks of apoptosis involving altered nuclear morphology and cleavage of poly(ADP-ribose) polymerase and of caspase 3 in both wild-type and SBMA cell lines. The caspase inhibitor VAD-fmk was able to decrease loss of viability of both cell lines on exposure to androgen.
Grierson
A J
AJ
Departments of Neuroscience and Neurology, Institute of Psychiatry, De Crespigny Park, Denmark Hill, SE5 8AF, London, UK.
Shaw
C E
CE
Miller
C C
CC
D017209:Apoptosis; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D015741:Metribolone / Q000494:pharmacology*; D016472:Motor Neuron Disease / Q000235:genetics / Q000473:pathology*; D009154:Mutation; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D045165:Testosterone Congeners / Q000494:pharmacology*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects
D011944:Receptors, Androgen; D045165:Testosterone Congeners; D015741:Metribolone