Apolipoprotein D is involved in the mechanisms regulating protection from oxidative stress.
Many 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.
Ganfornina
Maria D
MD
Departamento de Bioquímica y Biología Molecular y Fisiología-IBGM, Universidad de Valladolid-CSIC, 47003 Valladolid, Spain.
Do Carmo
Sonia
S
Lora
Jose M
JM
Torres-Schumann
Sonia
S
Vogel
Marci
M
Allhorn
Maria
M
González
Constancio
C
Bastiani
Michael J
MJ
Rassart
Eric
E
Sanchez
Diego
D
D000375:Aging / Q000187:drug effects; D000818:Animals; D053399:Apolipoproteins D / Q000235:genetics / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007858:Learning / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D054834:Lipocalins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects; D009420:Nervous System / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010269:Paraquat / Q000494:pharmacology; D016019:Survival Analysis; D019076:Transgenes; D015854:Up-Regulation / Q000187:drug effects
C024328:APOD protein, human; D053399:Apolipoproteins D; D006023:Glycoproteins; D054834:Lipocalins; D026901:Membrane Transport Proteins; D010269:Paraquat