Stress-induced heat shock protein 27 expression and its role in dorsal root ganglion neuronal survival.
Heat shock protein 27 (Hsp27), a molecular chaperone ubiquitously expressed in many cell types, has been shown to play a role in protecting neurons from cellular stresses. Unlike adult DRG neurons in vitro, neonatal DRG neurons require NGF for survival; withdrawal of NGF results in apoptosis of a majority of neonatal neurons. We hypothesized that Hsp27 contributes to the neurotrophin-independent survival of adult DRG neurons. Constitutive Hsp27 expression is higher in adult DRG neurons compared to neonates, although both upregulate Hsp27 expression after heat shock (HS). We found that increasing endogenous Hsp27 by HS in neonatal neurons was able to inhibit NGF withdrawal-induced apoptosis. Heat shock of adult and neonatal neurons also resulted in Akt activation, which could be a mechanism for the increased survival. Hsp27 siRNA treatment of adult neurons effected a decreased expression of Hsp27, which correlated with increased apoptosis in these neurons. Downregulation of Hsp27 via siRNA also blocked the HS-induced rescue of neonatal neurons after NGF withdrawal. These results indicate that physiologically induced upregulation of Hsp27 is sufficient to provide some degree of neuronal protection. Further, this induction appears to be regulated by the transcriptional activation of HSF1 as shown by HSF1 nuclear translocation and by EMSA analyses of HSF1 binding to nuclear protein.
Dodge
M Elaine
ME
Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada A1B 3V6.
Wang
Jinguo
J
Guy
Clifford
C
Rankin
Sherri
S
Rahimtula
Masuma
M
Mearow
Karen M
KM
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D015153:Blotting, Western; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D005727:Ganglia, Spinal / Q000166:cytology* / Q000502:physiology*; D055551:HSP27 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000502:physiology*; D006358:Hot Temperature; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D018696:Neuroprotective Agents; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013312:Stress, Physiological / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation / Q000502:physiology
D004268:DNA-Binding Proteins; D055551:HSP27 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C000619709:Hsf1 protein, rat; C486114:Hspb1 protein, rat; D009363:Neoplasm Proteins; D018696:Neuroprotective Agents; D034741:RNA, Small Interfering; D014157:Transcription Factors