Early involvement of lysosome dysfunction in the degeneration of cerebral cortical neurons caused by the lipid peroxidation product 4-hydroxynonenal.

ABSTRACT: Free radical-mediated oxidative damage to proteins, lipids, and DNA occurs in neurons during acute brain injuries and in neurodegenerative disorders. Membrane lipid peroxidation contributes to neuronal dysfunction and death, in part by disrupting neuronal ion homeostasis and cellular bioenergetics. Emerging findings suggest that 4-hydroxynonenal (HNE), an aldehyde produced during lipid peroxidation, impairs the function of various proteins involved in neuronal homeostasis. Here we tested the hypothesis that HNE impairs the cellular system that removes damaged proteins and organelles, the autophagy-lysosome pathway in rat primary cortical neurons. We found that HNE, at a concentration that causes apoptosis over a 48-72 h period, increases protein levels of LC3 II and p62 and within 1 and 4 

SUBMITTER: Zhang S 

PROVIDER: S-EPMC5339057 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature