NR AQTS
AU Shyu,W.C.; Lin,S.Z.; Saeki,K.; Kubosaki,A.; Matsumoto,Y.; Onodera,T.; Chiang,M.F.; Thajeb,P.; Li,H.
TI Hyperbaric oxygen enhances the expression of prion protein and heat shock protein 70 in a mouse neuroblastoma cell line
QU Cellular and Molecular Neurobiology 2004 Apr; 24(2): 257-68
PT journal article
AB 1. Cellular prion protein, PrPc, is a ubiquitous glycoprotein strongly expressed in neurons with an as yet unknown biological function. In previous studies, we demonstrated that PrPc could be regulated by heat shock stress, implying that it might be a stress-responsive protein. Hyperbaric oxygen (HBO) administration is a well-defined model for the study of oxidative stress. 2. This study investigated the effect of HBO on PrPc and Hsp 70 expression in mouse neuroblastoma cell lines (N18), assessing the expression of PrPc and Hsp 70 using RT-PCR and Western blotting. HBO administration resulted in a time- and dose-dependent increase in PrPc and Hsp70 expression in N18 cells at both mRNA and protein levels, with a concomitant upregulation of c-Jun N-terminal kinase (JNK). 3. Under HBO treatment, luciferase reporter constructs of the rat PrPc promoter, containing the heat shock element (HSE) also present in Hsp70, expressed higher luciferase activity (3- to 10-fold) than those constructs without HSE. 4. In summary, these data suggest that PrPc and Hsp 70 may be regulated by HBO, through the activation of JNK. Thus, the activated heat shock transcriptional factor 1, phosphorylated by JNK interacted with HSE in the promoter of PrPc resulted in increased gene expression. These findings are vital for future therapeutic approaches in transmissible spongiform encephalopathies and the understanding of the function of the PrPc.
MH Animals; Brain/metabolism/physiopathology; Cell Line, Tumor; DNA-Binding Proteins/drug effects/genetics; Dose-Response Relationship, Drug; Gene Expression Regulation/drug effects/genetics; Heat-Shock Proteins 70/drug effects/genetics/*metabolism; Hyperbaric Oxygenation; Luciferase/genetics; Mice; Mitogen-Activated Protein Kinases/drug effects/metabolism; Neuroblastoma; Neurons/drug effects/*metabolism; Oxidative Stress/drug effects/*physiology; Oxygen/*pharmacology; Phosphorylation; PrPc Proteins/drug effects/genetics/*metabolism; Promoter Regions (Genetics)/drug effects/genetics; RNA, Messenger/drug effects/metabolism; Support, Non-U.S. Gov't; Time Factors; Up-Regulation/drug effects/physiology
AD Neuro-Medical Scientific Center, Tzu-Chi Buddhist General Hospital, Tzu-Chi University, Hualien, Taiwan, Republic of China. shyu9423@sinamail.com
SP englisch
PO USA