Artículos de revistas
Elevated testosterone induces apoptosis in neuronal cells
Fecha
2006Registro en:
Journal of Biological Chemistry, Volumen 281, Issue 35, 2018, Pages 25492-25501
00219258
1083351X
10.1074/jbc.M603193200
Autor
Estrada, Manuel
Varshney, Anurag
Ehrlich, Barbara E.
Institución
Resumen
Testosterone plays a crucial role in neuronal function, but elevated concentrations can have deleterious effects. Here we show that supraphysiological levels of testosterone (micromolar range) initiate the apoptotic cascade. We used three criteria, annexin V labeling, caspase activity, and DNA fragmentation, to determine that apoptotic pathways were activated by testosterone. Micromolar, but not nanomolar, testosterone concentrations increased the response in all three assays of apoptosis. In addition, testosterone induced different concentration-dependent Ca2+ signaling patterns: at low concentrations of testosterone (100 nM), Ca2+ oscillations were produced, whereas high concentrations (1-10 μM) induced a sustained Ca2+ increase. Elevated testosterone concentrations increase cell death, and this effect was abolished in the presence of either inhibitors of caspases or the inositol 1,4,5-trisphosphate receptor (InsP 3R)-mediated Ca2+ release. Knockdown of InsP3R type 1 with specific sm