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Apoptosis

, Volume 14, Issue 11, pp 1274–1288 | Cite as

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

  • S. Steiger-Barraissoul
  • A. Rami
Original Paper

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 cells Autophagy Caspase-3 AIF LC3 Beclin-1 

Notes

Acknowledgments

This work was supported by the Adolf-Messer-Stiftung (Grant to Dr. A. Rami-Molecular mechanisms of autophagy). We thank J. Stehle for scientific support of our work, E. Maronde and A. Benz for helpful discussions.

Conflict of interest

The authors declare that they have no conflict of interest.

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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

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