Halbe Luisa and Rami Abdelhaq* Pages 1 - 8 ( 8 )
ER stress induced the mobilization of two protein breakdown routes, the proteasomaland autophagy-associated degradation. During ER- associated degradation, unfolded ER proteins are translocated to the cytosol where they are cleaved by the proteasome. When the accumulation of misfolded or unfolded proteins excels the ER capacity, autophagy can be activated in order to undertake the degradative machinery and to attenuate the ER stress. Autophagy is a mechanism by which macromolecules and defective organelles are included in autophagosomes and delivered to lysosomes for degradation and recycling of bioenergetics substrate.Autophagy upon ER stress serves initially as a protective mechanism, however when the stress is more pronounced the autophagic response will trigger cell death. As autophagy could function as a double-edged sword in cell viability, we examined the effects autophagy modulation on ER stressinduced cell death in HT22 murine hippocampal neuronal cells. We investigated the effects of both autophagy-inhibition by 3-methyladenine and autophagy-activation by trehalose on ER-stress induced damage in hippocampal HT22 neurons. We evaluated the expression of ER stress- and autophagy-sensors as well as the neuronal viability. Based on our findings, we conclude that under ER-stress conditions, inhibition of autophagy exacerbates cell damage and induction of autophagy by trehalose failed to be neuroprotective.
Autophagy, HT22 neurons, ER stress, trehalose, cell death.
Institut für Zelluläre und Molekulare Anatomie (Anatomie III), Klinikum der Johann Wolfgang von Goethe-Universität, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Institut für Zelluläre und Molekulare Anatomie (Anatomie III), Klinikum der Johann Wolfgang von Goethe-Universität, Theodor-Stern-Kai 7, 60590 Frankfurt/Main