Apolipoprotein D subcellular distribution pattern in neuronal cells during oxidative stress

Apolipoprotein D (Apo D) is a secreted glycoprotein, member of the lipocalin superfamily, with a related beneficial role in metabolism and lipid transport due to the presence of a binding pocket that allows its interaction with several lipids. Nowadays, it has been clearly demonstrated that Apo D expression is induced and its subcellular location undergoes modifications in stressful and pathological conditions that characterize aging processes and neurodegenerative diseases. The aim of the present work was to study in detail the effect of H2O2 on the subcellular location of Apo D, in the hippocampal cell line HT22, by structural, ultrastructural, immunocytochemical, and molecular techniques in order to characterize the Apo D distribution pattern in neurons during oxidative stress. Our results indicate that Apo D is located in the cytoplasm under physiological conditions but treatment with H2O2 induces apoptosis and causes a displacement of Apo D location to the nucleus, coinciding with DNA fragmentation. In addition, we demonstrated that Apo D tends to accumulate around the nuclear envelope in neurons and glial cells of different brain areas in some neurodegenerative diseases and during human aging, but never inside the nucleus. These data suggest that the presence of Apo D in the nucleus, which some authors related with a specific transport, is a consequence of structural and functional alterations during oxidative stress and not the result of a specific role in the regulation of nuclear processes.