Barbati, Cristiana (2012) Ruolo degli estrogeni nella modulazione dell'apoptosi e dell'autofagia in cellule neuronali. Doctoral Thesis.
The role of E2 as well as of the membrane estrogen receptors (mER) in governing either apoptosis or autophagy have been evaluated. SH-SY5Y neuroblastoma cells and rat primary embryonic hippocampal neurons were treated with hydrogen peroxide for 7 days to induce chronic oxidative stress (SOC). The intracellular and cell surface expression of ER was detected by flow and static cytometry. After 48h of E2 or E2BSA (a membrane-impermeant form of E2) treatment, autophagy level (LC3-II level) and signal transduction pathways (ERK phosphorylation/p-38) were analyzed by western blot, and apoptosis (annexin V and Bcl-2 expression) by flow cytometry analysis. Our results showed that ERalpha and ERbeta were expressed at intracellular, but not at cells surface, level. Under chronic oxidative stress condition, mERalpha was expressed at the neuronal cell surface of both SH-SY5Y and rat neurons. E2 or E2BSA treatment protected cells from apoptosis induced by SOC (i.e., decreased annexin V expression and decreased p38 signaling, increased anti-apoptotic Bcl-2 protein level). Moreover, E2 or E2BSA induced a significant increase of autophagy, i.e., an increase of LC3-II level and of ERK phosphorylation. We actually found that under unfavorable conditions, i.e. mimicking an inflammatory microenvironment, the up-regulation of the expression of mERalpha could represent an important controller of cell fate. Estrogens may play an important role in governing either apoptosis or autophagy in neurons.
I documenti depositati in UnissResearch sono protetti dalle leggi che regolano il diritto d'autore
Repository Staff Only: item control page