Apoptosis

, Volume 14, Issue 11, pp 1274–1288

Serum deprivation induced autophagy and predominantly an AIF-dependent apoptosis in hippocampal HT22 neurons

Original Paper

DOI: 10.1007/s10495-009-0396-9

Cite this article as:
Steiger-Barraissoul, S. & Rami, A. Apoptosis (2009) 14: 1274. doi:10.1007/s10495-009-0396-9

Abstract

Neuronal death induced by serum deprivation (SD) in HT22-cells was accompanied by a moderate activation of caspase-3, a prominent upregulation of AIF and its translocation into the nucleus. In addition protein levels of autophagy markers such as LC3 and beclin-1 were affected by SD. The ratio of LC3-II/LC3-I was significantly increased in serum deprived cultures. Furthermore, the addition of the pan-caspase inhibitor z-VAD(OMe)-FMK (zVAD) does not protect HT22-cells from SD-induced neurodegeneration. However, addition of the autophagy inhibitors such as 3-methyladenine (3-MA) or bafilomycin A1 (BafA1) provided a potentiation of cell death induced by SD. z-VAD and 3-MA in combination were not only ineffective in rescuing cells from the damaging effects of SD, but seem likely to act in synergy to potentiate slightly SD-induced cell death. The results of the current study suggest that SD induced predominantly caspase-independent apoptosis in hippocampal HT22 cells and that inhibition of autophagy is rather deleterious than protective.

Keywords

HT22 cellsAutophagyCaspase-3AIFLC3Beclin-1

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Dr. Senckenbergische Anatomie, Institute of Cellular and Molecular AnatomyClinics of the Wolfgang Goethe-UniversityFrankfurt/MainGermany