Induction of rat L-phosphoserine phosphatase by amyloid-beta (1-42) is inhibited by interleukin-11.
Alzheimer's disease (AD) is characterized by the presence of beta-amyloid (Abeta) protein deposits in the brain and increased Abeta (1-42) peptide production is thought to be one of the early events in the pathogenesis of AD that leads to progressive neurodegenerative processes and dementia. Using cDNA subtraction and reverse transcription-polymerase chain reaction, we examined the Abeta (1-42) peptide-induced gene expression in rat neuroblastoma B104 cells. In addition we hypothesized that interleukin-11 (IL-11) supports neuronal survival. We found that Abeta (1-42) activates L-phosphoserine phosphatase in neuronal cells which is inhibited by IL-11. Moreover, IL-11 inhibits Abeta (1-42)-induced neurotoxicity in a dose-dependent manner. Our study suggests that L-phosphoserine phosphatase may play a role in altered neuronal function in AD via enhancing glutamate-induced neurotoxicity by D-serine and the IL-11 receptor system may act as a neuroprotective cytokine in human brain.
Heese
K
K
BF Research Institute, Inc., c/o National Cardiovascular Center, Osaka, Japan. heesek@silver.ocn.ne.jp
Nagai
Y
Y
Sawada
T
T
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D015139:Blotting, Southern; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D017370:Interleukin-11 / Q000494:pharmacology*; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D018123:Receptors, Interleukin / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012694:Serine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D017370:Interleukin-11; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D016194:Receptors, N-Methyl-D-Aspartate; C075222:amyloid beta-protein (1-42); D012694:Serine; D010744:Phosphoric Monoester Hydrolases; C022394:phosphoserine phosphatase