Evidence for caspase effects on release of cytochrome c and AIF in a model of ischemia in cortical neurons

Abstract

Neuronal apoptosis following ischemia can be mediated by a caspase-dependent pathway, which involves the mitochondrial release of cytochrome c that initiates a cascade of caspase activation. In addition, there is a caspase-independent pathway, which is mediated by the release of apoptosisinducing factor (AIF). Using caspase-inhibitor gene therapy, we investigated the roles of caspases on the mitochondrial release of cyt c and the release of AIF. Specifically, we used herpes simplex virus-1 amplicon vectors to ectopically express a viral caspase inhibitor (crmA or p35) in mixed cortical cultures exposed to oxygen/glucose deprivation. Overexpression of either crmA or p35 (but not the caspase-3 inhibitor DEVD) inhibited the release of AIF; this suggests that there can be crosstalk between the caspase-dependent and the ostensibly caspase-independent pathway. In addition, both crmA overexpression and DEVD inhibited cyt c release, suggesting a positive feedback loop involving activated caspases stimulating cyt c release.

Dihydrotanshinone I induced apoptosis and autophagy through caspase dependent pathway in colon cancer

“…In accordance with these reports, our study also showed a significant decrease of DHTS-induced cytochrome c release from mitochondria after AIF knockdown in HCT116 cells. At the same time, AIF release was reported to be either caspase-dependent or caspaseindependent (Singh et al, 2010). For instance, caspases-3 and -7 are crucial for apoptosis and contribute to some mitochondrial events including the translocation of AIF (Arnoult et al, 2002;Lakhani et al, 2006).…”

Early Exercise Protects against Cerebral Ischemic Injury through Inhibiting Neuron Apoptosis in Cortex in Rats

“…Clinical evidence showed that apoptosis occurred in the penumbral region from 1 to 26 days after stroke [18,19]. Thus, suppressing apoptosis at early stage after stroke may be an important opportunity for salvage of neurons in penumbra, and then reduce the infarct volume and alleviate brain injury induced by ischemia [20–22]. …”

Derivation of Injury-Responsive Dendritic Cells for Acute Brain Targeting and Therapeutic Protein Delivery in the Stroke-Injured Rat

“…Mixed neuronal/glial cortical or hippocampal cultures were prepared from day 18 fetal SD rats [46], [28]. On DIV 12, cortical cultures were treated with OGD and hippocampal cultures were treated with glutamate [46], [28].…”

“…On DIV 12, cortical cultures were treated with OGD and hippocampal cultures were treated with glutamate [46], [28]. Following OGD or concomitant to glutamate exposure, neuronal cultures were treated with vehicle (MEM, Gibco), GFP-DCs, hBDNF-DCs, or tBH4-DCs (1000 DCs/well) and assayed for neuron death 24 hours post-insult onset [47].…”