Lipoxygenases and poly(ADP-ribose) polymerase in amyloid beta cytotoxicity

Strosznajder, Joanna B. and Cieslik, Magdalena and Cakala, Magdalena and Jesko, Henryk and Eckert, Anne and Strosznajder, Robert P.. (2011) Lipoxygenases and poly(ADP-ribose) polymerase in amyloid beta cytotoxicity. Neurochemical research, Vol. 36, H. 5. pp. 839-848.

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Official URL: http://edoc.unibas.ch/dok/A6007031

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The 12/15-lipoxygenase(s) (LOX), poly(ADP-ribose) polymerase (PARP-1) activity and mitochondrial apoptosis inducing factor (AIF) protein in the amyloid ? (A?) toxicity were investigated in PC12 cells that express either wild-type (APPwt) or double Swedish mutation (APPsw) forms of human A? precursor protein. Different levels of A? secretion and free radicals formation characterize these cells. The results demonstrated a relationship between the A? levels and LOX protein expression and activity. High A? concentration in APPsw cells correlated with a significant increase in free radicals and LOX activation, which leads to translocation of p65/NF-?B into the nucleus. An increase in AIF expression in mitochondria was observed concurrently with inhibition of PARP-1 activity in the nuclear fraction of APPsw cells. We suggested that AIF accumulation in mitochondria may be involved in adaptive/protective processes. However, inhibition of PARP-1 may be responsible for the disturbances in transcription and DNA repair as well as the degeneration of APP cells. Under conditions of increased nitrosative stress, evoked by the nitric oxide donor, sodium nitroprusside (SNP, 0.5 mM), 70-80% of all cells types died after 24 h, significantly more in APPsw cells. There was no further significant change in mitochondrial AIF level and PARP-1 activity compared to corresponding non-treated cells. Only one exception was observed in PC12 control, where SNP significantly inhibits PARP-1 activity. Moreover, SNP significantly activated gene expression for 12/15-LOX in all types of investigated cells. Inhibitors of all LOX isoforms and specific inhibitor of 12-LOX enhanced the survival of cells that were subjected to SNP. We conclude that the LOX pathways may play a role in A? toxicity and in nitrosative-stress-induced cell death and that inhibition of these pathways offers novel protective strategies.
Faculties and Departments:03 Faculty of Medicine > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Erwachsenenpsychiatrie (Lang)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Erwachsenenpsychiatrie (Lang)
UniBasel Contributors:Eckert, Anne
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Plenum Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:25 Oct 2013 08:32
Deposited On:25 Oct 2013 08:32

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