Apolipoprotein D is involved in the mechanisms regulating protection from oxidative stress

Abstract

SummaryMany nervous system pathologies are associated with increased levels of apolipoprotein D (ApoD), a lipocalin also expressed during normal development and aging. An ApoD homologous gene in Drosophila , Glial Lazarillo, regulates resistance to stress, and neurodegeneration in the aging brain. Here we study for the first time the protective potential of ApoD in a vertebrate model organism. Loss of mouse ApoD function increases the sensitivity to oxidative stress and the levels of brain lipid peroxidation, and impairs locomotor and learning abilities. Human ApoD overexpression in the mouse brain produces opposite effects, increasing survival and preventing the raise of brain lipid peroxides after oxidant treatment. These observations, together with its transcriptional up-regulation in the brain upon oxidative insult, identify ApoD as an acute response protein with a protective and therefore beneficial function mediated by the control of peroxidated lipids.

Expression and potential role of apolipoprotein D on the death–survival balance of human colorectal cancer cells under oxidative stress conditions

“…ApoD is upregulated by, and protects against, oxidative stress [9,13,15]. As reported here and in other works, ApoD expression is maintained at general low levels in tumor tissues, which, along with its positive regulation by growth arrest [38], supports the proposal made by several authors that ApoD is a tumor suppressor gene [30].…”

“…We have previously shown in PQ-challenged astrocyte primary cultures that the concentration of ApoD is critical for its protective effect [16]. An excess of ApoD appears to be detrimental for cell survival, a result also supported by the fact that ApoD gene transcription is transient in response to OS [13,16]. Our data show that the situation in the colorectal tissue would in fact be more complex.…”

“…Inducing OS by treatment with the ROS generator paraquat (PQ), we have demonstrated a protective function of ApoD in the organism survival. This effect was associated with a role in regulating tissue homeostasis and in maintaining low levels of lipid peroxidation [13][14][15]. We have recently shown that ApoD contributes to reduce inflammation levels in ROS-injured tissues and promotes the clearance of lipid peroxides in cells [16,17].…”

“…The treatment of HT-29 cells with the ROS generator paraquat (PQ), which induces ApoD expression in these cells (Fig. 6a) and in a number of experimental models [13,15,16], shows a dramatic effect on both cell proliferation and cell death (Fig. 6c, d).…”

Apolipoprotein D mediates autocrine protection of astrocytes and controls their reactivity level, contributing to the functional maintenance of paraquat-challenged dopaminergic systems

“…Apolipoprotein D (ApoD), a member of the Lipocalin family secreted by astrocytes and oligodendrocytes, but not expressed in microglia, is known to mediate protective effects for the organism under OS (Ganfornina et al, 2008). The homologues of ApoD in Drosophila, GLaz and NLaz, protect against oxidative damage and contribute significantly to the regulation of longevity (HullThompson et al, 2009;Ruiz et al, 2011;Sanchez et al, 2006;Walker et al, 2006).…”