Neuroprotective Effect of Sodium Orthovanadate on Delayed Neuronal Death after Transient Forebrain Ischemia in Gerbil Hippocampus

Abstract

In transient forebrain ischemia, sodium orthovanadate as well as insulinlike growth factor-1 (IGF-1) rescued cells from delayed neuronal death in the hippocampal CA1 region. Adult Mongolian gerbils were subjected to 5-minute forebrain ischemia. Immunoblotting analysis with anti-phospho-Akt/PKB (Akt) antibody showed that phosphorylation of Akt at serine-473 (Akt-Ser-473) in the CA1 region decreased immediately after reperfusion, and in turn transiently increased 6 hours after reperfusion. The decreased phosphorylation of Akt-Ser-473 was not observed in the CA3 region. The authors then tested effects of intraventricular injection of orthovanadate and IGF-1, which are known to activate Akt. Treatment with orthovanadate or IGF-1 30 minutes before ischemia blocked delayed neuronal death in the CA1 region. The neuroprotective effects of orthovanadate and IGF-1 were associated with preventing decreased Akt-Ser-473 phosphorylation in the CA1 region observed immediately after reperfusion. Immunohistochemical studies with the anti-phospho-Akt-Ser-473 antibody also demonstrated that Akt was predominantly in the nucleus and was moderately activated in the cell bodies and dendrites of pyramidal neurons after orthovanadate treatment. The orthovanadate treatment also prevented the decrease in phosphorylation of mitogen-activated protein kinase (MAPK). Pretreatment with combined blockade of phosphatidylinositol 3-kinase and MAPK pathways totally abolished the orthovanadate-induced neuroprotective effect. These results suggest that the activation of both Akt and MAPK activities underlie the neuroprotective effects of orthovanadate on the delayed neuronal death in the CA1 region after transient forebrain ischemia.

Maintenance of Bad Phosphorylation Prevents Apoptosis of Rat Hepatic Sinusoidal Endothelial Cells in Vitro and in Vivo

“…[47][48][49][50] Interestingly, recent studies have shown that OV treatment rescues neuronal death of the gerbil and rat hippocampus after transient ischemia via PI3K/ Akt and MAPK pathways. 51,52 It has also been reported that OV protects cardiomyocytes from ischemia-reperfusion injury in the rat heart through Akt activation. 53 Our data are consistent with a recent report demonstrating that adenoviral gene transfer of the constitutively active form of Akt protects the rat liver from ischemia-reperfusion injury with increased phosphorylation of Bad at Ser-136.…”

Cardioprotection by Vanadium Compounds Targeting Akt-Mediated Signaling

“…Indeed, both Fas ligand and Bim are induced in the ventricular cardiomyocyte after myocardial ischemia/reperfusion-induced injury (18,30). Moreover, we previously documented the FOXOs-mediated increased expression of Fas ligand and Bim in ischemic brain injury in a mouse bilateral common carotid artery occlusion model (61,62,66,67). VO(OPT) treatments prevented ischemia/reperfusion injury-induced expression of Fas ligand and Bim in rat heart (18,19) and brain (51).…”

Pattern of Transcription Factor Activation in Helicobacter pylori–Infected Mongolian Gerbils

“…These antibodies have been reported to cross-react with Mongolian gerbils. [16][17][18][19][20] Cytoplasmic extract (10 µg per sample) obtained during the preparation of nuclear extracts was fractionated by SDS-PAGE and electrophoretically transferred to a polyvinylidene difluoride membrane. Detection was performed using ECL reagents (Amersham Life Science, Arlington Heights, IL).…”