The up-regulation of endosomal-lysosomal components in amyloid beta-resistant cells.
The abundance of amyloid beta peptide (A beta) and the selective loss of neurons are characteristics of Alzheimer's disease. However, subpopulations of brain cells survive, including neurons near A beta-rich plaques. The surviving neurons may have gene expression profiles that allow them to be resistant to A beta toxicity. Here we use the differential display technique to compare the profiles of gene expression in an A beta-resistant cell line with its parental cells. Prominent among the changes are two components of the endosomal-lysosomal system, insulin growth factor II receptor/mannose-6-phosphate receptor and arylsulfatase B. Both are more highly expressed in the A beta-resistant clone, and arylsulfatase is inducible by A beta and hydrogen peroxide. Another lysosomal enzyme, beta-glucuronidase, is also up-regulated in A beta-resistant cells. These results are consistent with the observation that the endosomal-lysosomal system is highly activated in Alzheimer's disease brains, and they raise the possibility that the high expression of endosomal-lysosomal components is important for neuronal survival in the presence of A beta.
Li
Y
Y
The Salk Institute, La Jolla, California, USA.
Xu
C
C
Schubert
D
D
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D004351:Drug Resistance; D011992:Endosomes / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005966:Glucuronidase / Q000235:genetics; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008247:Lysosomes / Q000378:metabolism*; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000235:genetics*; D016716:PC12 Cells; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017527:Receptor, IGF Type 2 / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects
D016229:Amyloid beta-Peptides; D012333:RNA, Messenger; D017527:Receptor, IGF Type 2; D006861:Hydrogen Peroxide; D020051:N-Acetylgalactosamine-4-Sulfatase; D005966:Glucuronidase