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

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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.

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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.

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The authors declare that they have no conflict of interest.

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  1. Dr. Senckenbergische Anatomie, Institute of Cellular and Molecular Anatomy, Clinics of the Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590, Frankfurt/Main, Germany

    S. Steiger-Barraissoul & A. Rami

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Correspondence to A. Rami.

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Steiger-Barraissoul, S., Rami, A. Serum deprivation induced autophagy and predominantly an AIF-dependent apoptosis in hippocampal HT22 neurons. Apoptosis 14, 1274–1288 (2009). https://doi.org/10.1007/s10495-009-0396-9

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