title: 4-Hydroxynonenal disrupts zinc export in primary rat cortical cells.
abstract: Accumulating evidence implicates oxidative stress in the pathogenesis of several neurodegenerative disorders including Alzheimer's disease (AD). Increased lipid peroxidation, decreased levels of polyunsaturated fatty acids, and increased levels of 4-hydroxynonenal (HNE) have been demonstrated in AD brain. Proteins responsible for zinc export are localized on the plasma membrane and may be vulnerable to damage from lipid peroxidation. To test this hypothesis, cultured primary rat cortical neurons were incubated with (65)Zn for 1h and then treated with HNE (0-35 microM) for 4 h. Levels of (65)Zn in aliquots of medium were measured at 1, 2, 4h following treatment with HNE and intracellular (65)Zn measured after 4h using liquid scintillation counting. The amount of (65)Zn in medium did not differ significantly. However, a statistically significant (p<0.05) increase of (65)Zn was observed inside cortical neurons after treatment with 20 microM HNE for 4 hours. These data suggest that HNE may impair a protein essential for zinc export leading to increased levels of intracellular zinc.
authors.affiliation: Department of Chemistry, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Smith
authors.forename: S
authors.initials: S
authors.lastname: Xiong
authors.forename: M A
authors.initials: MA
authors.lastname: Lovell
mesh_terms: D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D027682:Cation Transport Proteins; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008565:Membrane Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D015032:Zinc / Q000378:metabolism*
chemical_list: D000447:Aldehydes; D027682:Cation Transport Proteins; D008565:Membrane Proteins; C092392:Slc30a1 protein, rat; D015032:Zinc; C027576:4-hydroxy-2-nonenal