Hypoglycemia enhances the expression of prion protein and heat‐shock protein 70 in a mouse neuroblastoma cell line

Cellular prion protein (PrP C ) expression can be regulated by heat‐shock stress, and we designed the present study to determine whether hypoglycemia could affect PrP C expression. RT‐PCR and Western blotting were used to measure the expression of PrP C and heat‐shock protein (Hsp70) in mouse neuroblastoma (N18) cells cultured 3 hr to 3 days in media deprived of 97.5% (L) or 75% (M) of its glucose. Hypoglycemia caused a concomitant time‐dependent and glucose dose‐dependent increase in PrP C and Hsp70. In addition, hypoglycemia also increased phosphorylated c‐Jun N‐terminal kinase (JNK) protein levels in a time‐dependent manner. The upregulation of PrP C and Hsp70 under hypoglycemic conditions was disrupted by the specific JNK inhibitor SP600125. It was also found from in vitro studies that hypoglycemic conditions induced higher levels of PrP C promoter activity in PrP C promoters containing a heat‐shock element (HSE) than in PrP C promoters lacking HSE. We propose that hypoglycemia‐increased PrP C expression might be due to JNK phosphorylation of a heat‐shock transcriptional factor, which then interacts with HSE in the promoter of PrP C . © 2005 Wiley‐Liss, Inc.