Induction of glucose-regulated protein (glucose-regulated protein 78/BiP and glucose-regulated protein 94) and heat shock protein 70 transcripts in the immature rat brain following status epilepticus.
Prior to 21 days of age, the immature rat brain is relatively resistant to excitotoxicity caused by the glutamate analogue, kainate. As stress-inducible proteins (GRP78, GRP94 and HSP70) have been proposed to possess molecular chaperone activity and protect cells from the deleterious effects of damaged proteins, we examined the pattern of expression of their respective messenger RNAs following systemic kainate at different postnatal ages. In untreated rats between seven and 21 days old, there was a higher basal level of grp78 and grp94 expression compared to hsp70. Unlike hsp70, which was inducible only in 21-day-old rats, kainate-mediated grp94 induction occurred in several regions of the brain as early as postnatal day 7. Grp78 messenger RNA expression was also increased by kainate treatment in 14-day-old rats, and the induction was most pronounced in the kainate-resistant dentate gyrus. With increasing age, longer lasting expression of both grp78 and grp94 messenger RNAs was observed in kainate-vulnerable regions, similar to observations in the adult rat brain. These results demonstrate non-overlapping expression patterns of glucose-regulated proteins and HSP70 in the immature central nervous system, suggesting that they serve different functions. While hsp70 induction could be a marker for potential cell injury and death, increased expression of grp78 and grp94 could play a neuroprotective role in the developing rat brain.
Little
E
E
Department of Biochemistry, University of Southern California, School of Medicine, Los Angeles 90033, USA.
Tocco
G
G
Baudry
M
M
Lee
A S
AS
Schreiber
S S
SS
D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006360:Heat-Shock Proteins; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D018832:Molecular Chaperones / Q000096:biosynthesis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C018551:glucose-regulated proteins; D007608:Kainic Acid