Background: 4, hydroxyl trans-2-nonenal (HNE) is the most reactive aldehyde generated from the lipid peroxidation reactions. The biological effects of HNE are dependent on the metabolism of HNE. Purpose: To examine the metabolism of HNE in PC-12 cells and to study the cytotoxic effects of HNE as well as the effect of non-toxic concentrations of HNE on neurotransmitter receptors. Methods: After the incubation, cells were separated from the incubation medium and the radio labeled metabolites extruded in the medium were resolved by reverse phase HPLC and analyzed by ESI/MS or GC/MS. Results: Our data shows that in PC-12 cells, at low (physiological) concentrations HNE is primarily metabolized by glutathiolation and oxidation, whereas at higher (pathological) concentrations, in addition to glutathiolation and oxidation, a significant fraction of HNE is reduced in PC-12 cells. Mass spectroscopic analysis also shows that glutathionyl adduct of HNE is present as two forms-GS-HNE and its reduced metabolite GS-DHN. However, unlike the cardiovascular cells, reduction of GS-HNE is not catalyzed by aldose reductase, since inhibition of aldose reductase, did not abolish the reduction of GS-HNE in PC-12 cells. Conclusion: Aldehyde dehydrogenase-mediated oxidation of HNE is an important route for the elimination of HNE in neuronal cells.

doi: 10.5214/ans.0972.7531.2008.150302 

Competing interests: None.  Source of Funding: CSIR, ICMR

Received Date: 14 July 2008     Revised Date: 25 July 2008     Accepted Date: 31 July 2008