Localization of heat shock proteins in cerebral cortical cultures following induction by celastrol.
Hsp70, Hsp32, and Hsp27 were induced by celastrol in rat cerebral cortical cultures at dosages that did not affect cell viability. Pronounced differences were observed in the cellular localization of these heat shock proteins in cell types of cerebral cortical cultures. Celastrol-induced Hsp70 localized to the cell body and cellular processes of neurons that were identified by neuron-specific βIII-tubulin. Hsp70 was not detected in adjacent GFAP-positive glial cells that demonstrated a strong signal for Hsp27 and Hsp32 in both glial cell bodies and cellular processes. Cells in the cerebral cortex region of the brain are selectively impacted during the progression of Alzheimer's disease which is a "protein misfolding disorder." Heat shock proteins provide a line of defense against misfolded, aggregation-prone proteins. Celastrol is a potential agent to counter this neurodegenerative disorder as recent evidence indicates that in vivo administration of celastrol in a transgenic model of Alzheimer's reduces an important neuropathological hallmark of this disease, namely, amyloid beta pathology that involves protein aggregation.
Centre for the Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON, M1C 1A4, Canada.
Ari M
AM
Chow
Derek W F
DW
Tang
Asad
A
Hanif
Ian R
IR
Brown
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005865:Gestational Age; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D053978:Pentacyclic Triterpenes; D017207:Rats, Sprague-Dawley; D014315:Triterpenes / Q000494:pharmacology*; D015854:Up-Regulation
D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D018696:Neuroprotective Agents; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; C050414:celastrol