Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Visna-Maedi virus (VMV), an ungulate lentivirus, causes a natural infection in sheep. In vitro, VMV infection and replication lead to strong cytopathic effects with subsequent death of host cells. We investigated, in vitro, the relative contribution of apoptosis or programmed cell death (PCD) to cell killing during acute infection with VMV, by employing diverse strategies to detect its common end-stage alterations. We demonstrated that VMV-infection in sheep choroid plexus cells (SCPC), is associated with apoptosis, characterized by morphological changes such as condensation of chromatin and the appearence of apoptotic bodies. DNA fragmentation was documented by TUNEL assay. Although the mechanism by which VMV activates this cell suicide program is not known, we examined the activation of caspases, the family of death-inducing proteases that resulted in cleavage of several cellular substrates. To study the role of caspases in VMV-induced apoptosis, we focused on several protease targets: procaspase-3 and procaspase-1. During VMV-infection, SCPC display active caspase-3 and no caspase-1 activity. In conclusion, our results suggest that VMV infection, in vitro, induces cell death of SCPC by a mechanism that can be characterized by many of the properties most closely associated with apoptotic cell death.
 ...
PMID:Visna virus-induced cytopathic effect in vitro is caused by apoptosis. 1202 66

Visna/maedi virus (VMV) causes severe encephalitis and a progressive demyelinating disease in sheep. Previous in vitro studies have demonstrated that VMV-infection leads to apoptosis in sheep choroid plexus cells (SCPC) via induction of both intrinsic and extrinsic pathways with subsequent activation of caspases. 3' azido-2',3'-deoxythymidine (AZT) is a potent and selective Human immunodeficiency virus 1 (HIV-1) reverse transcriptase inhibitor, widely used in antiretroviral therapy; however its effects on retrovirus-induced apoptosis are unknown. Using diverse strategies to detect apoptosis, we analysed the broad range effect of AZT treatment on inhibition of VMV-induced apoptosis. First, we found that AZT treatment inhibited the appearance of characteristic apoptotic morphologic changes documented by DAPI staining and oligonucleosomal DNA laddering. Secondly, AZT treatment inhibited caspase cascade and resulted in (i) diminished caspase-3, -8 and -9 activities and (ii) no fluorescein isothiocynate-[VAD]-fluoromethylketone (FITC-VAD-FMK) in situ labelling in VMV-infected cells treated with AZT. Finally, immunocytochemistry indicated that VMV-infection of SCPC induced the subsequent release of apoptosis inducing factor (AIF), whereas AZT treatment inhibited AIF leakage. Consequently, the anti-apoptotic effects of AZT are not restricted, since AZT treatment blocks all the apoptotic pathways induced during VMV-infection.
 ...
PMID:AZT inhibits Visna/maedi virus-induced apoptosis. 1499 45