Clusterin up-regulation following sub-lethal oxidative stress and lipid peroxidation in human neuroblastoma cells.
Clusterin/apolipoprotein J is a multifunctional protein up-regulated during various pathophysiological states. Since oxidative stress plays an important role in brain aging, and in many neurodegenerative disorders, to further understand the mechanistic underpinnings of clusterin expression, in this study, we examined clusterin expression in human neuroblastoma cells under conditions of increased production of reactive oxygen species and lipid peroxidation. Specifically, we analyzed clusterin mRNA and protein levels in human neuroblastoma IMR-32 and SH-SY5Y cells following exposure to sub-lethal amounts of iron-ascorbate to induce an increase in reactive oxygen species generation and lipid peroxidation. Under such conditions, we observed a time-dependent up-regulation of clusterin protein and mRNA levels, detected by immunoblot analysis and RT-PCR, respectively. Given the known roles of clusterin, the results of the present study support the notion that an increase in clusterin expression may be a physiological defence mounted to reduce cell damage and maintain cell viability during periods of increased oxidative stress.
Strocchi
Paola
P
Department of Pharmacology, University of Bologna, Bologna 40126, Italy. strocchi@biocfarm.unibo.it
Smith
Mark A
MA
Perry
George
G
Tamagno
Elena
E
Danni
Oliviero
O
Pession
Annalisa
A
Gaiba
Alessia
A
Dozza
Barbara
B
D000544:Alzheimer Disease; D001205:Ascorbic Acid / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D051152:Clusterin / Q000235:genetics / Q000378:metabolism*; D005296:Ferrous Compounds / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation; D009474:Neurons / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects
D051152:Clusterin; D005296:Ferrous Compounds; D016877:Oxidants; D017382:Reactive Oxygen Species; C020748:ferrous sulfate; D006861:Hydrogen Peroxide; D001205:Ascorbic Acid