Pharmacological Induction of Heme Oxygenase-1 by a Triterpenoid Protects Neurons Against Ischemic Injury
Ischemic injury
DOI:
10.1161/strokeaha.111.647420
Publication Date:
2012-03-30T04:43:00Z
AUTHORS (12)
ABSTRACT
Heme oxygenase-1 (HO-1) is an inducible Phase 2 enzyme that degrades toxic heme; its role in cerebral ischemia not fully understood. We hypothesize chemically induced HO-1 upregulation with the novel triterpenoid CDDO-Im (2-cyano-3,12 dioxooleana-1,9 dien-28-oyl imidazoline), a robust inducer of genes, protects neurons against ischemic injury.Using 3 different models ischemia, including oxygen-glucose deprivation neuronal cultures, global rats, and focal mice, we determined (1) whether induces expression injury; (2) inhibition disrupts neuroprotective effect CDDO-Im.CDDO-Im treatment (50-300 nmol/L) resulted 8-fold cultured protected deprivation. The protection was abolished when cultures were transfected nuclear factor (erythroid-derived 2) like-2-shRNA or coincubated tin protoporphyrin IX, specific inhibitor. In rat model intracerebroventricular infusion (0.5-1.5 μg) augmented hippocampal significant increases CA1 survival after ischemia. To further strengthen clinical relevance treatment, tested effects mouse temporary (60 minutes). Postischemic intraperitoneal injection (10-100 enhanced significantly reduced neurological dysfunction infarct volume. Intracerebroventricular IX ischemia.CDDO-Im confers neuroprotection injury by upregulating HO-1, suggesting enhance may be legitimate strategy for therapeutic intervention stroke.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (29)
CITATIONS (78)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....