Geldanamycin treatment reduces delayed CA1 damage in mouse hippocampal organotypic cultures subjected to oxygen glucose deprivation.
Our prior work demonstrated that geldanamycin (GA) reduced injury due to oxygen-glucose deprivation (OGD) in primary astrocyte cultures. Using medium with an ionic composition similar to that observed during in vivo global ischemia, the selectivity and temporal profile of CA1 neuronal damage seen in vivo was mimicked with OGD in mouse hippocampal organotypic slice cultures. The present study tested the ability of GA to reduce delayed neuronal death in such cultures. Treating organotypic cultures with 100 nM GA for 24 h prior to OGD induced Hsp70 and significantly reduced CA1 neuronal damage. Staining with ubiquitin to identify protein aggregates revealed reduced redistribution of ubiquitin, consistent with reduced protein aggregation likely due at least in part to induction of Hsp70 by GA.
Ouyang
Yi-Bing
YB
Department of Anesthesia, Grant Building S272, Stanford University School of Medicine, Stanford, CA 94305 5117, USA.
Xu
Lijun
L
Giffard
Rona G
RG
D000818:Animals; D016227:Benzoquinones; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency; D018840:HSP70 Heat-Shock Proteins / Q000819:agonists / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology; D047029:Lactams, Macrocyclic; D051379:Mice; D008954:Models, Biological; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009924:Organ Culture Techniques; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism; D017510:Protein Folding; D011809:Quinones / Q000494:pharmacology*; D013997:Time Factors; D016896:Treatment Outcome; D025801:Ubiquitin / Q000819:agonists / Q000378:metabolism
D016227:Benzoquinones; D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D018696:Neuroprotective Agents; D011809:Quinones; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; D005947:Glucose; C001277:geldanamycin