Serum deprivation induced autophagy and predominantly an AIF-dependent apoptosis in hippocampal HT22 neurons.
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.
Steiger-Barraissoul
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Institute of Cellular and Molecular Anatomy, Clinics of the Wolfgang Goethe-University, Frankfurt/Main, Germany.
Rami
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D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D016895:Culture Media, Serum-Free; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D018942:Macrolides / Q000494:pharmacology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009410:Nerve Degeneration / Q000378:metabolism
D000590:Amino Acid Chloromethyl Ketones; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D016895:Culture Media, Serum-Free; D018942:Macrolides; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; C476093:z-Val-Ala-Asp(Ome)-fluoromethylketone; C025946:3-methyladenine; C040929:bafilomycin A1; D053148:Caspase 3; D000225:Adenine