Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.62 (caspase-9)
 7,507 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals. This pathology is caused by foot-and-mouth disease virus (FMDV). Over time, the development of vaccines to prevent the spread of this illness became essential. Vaccines currently used contain the inactivated form of the virus. However, vaccination generates an immune response different to that induced by the infection. We investigated whether these differences are related to intracellular mechanisms on dendritic cells (DCs). As a result, we demonstrated that the internalization of infective virus triggered the phosphorylation of ERK1/2, which was involved in the activation of caspase-9, the intrinsic pathway of apoptosis and the delivery of viral peptides on MHC class I molecules. While, inactivated virus (iFMDV) did not affect this pathway or any function mediated by its activation. As described, infectious virus in DCs was also associated to autophagy LC3 protein and was associated to lysosomal protein Lamp-2; contrary to observe for the iFMDV. Strikingly, the processing of viral antigens to accommodate in class I molecules does not appear to involve the proteasome. Finally, this increased presentation promotes a specific cytotoxic response against infectious virus.
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PMID:Foot-and-mouth disease virus infection of dendritic cells triggers phosphorylation of ERK1/2 inducing class I presentation and apoptosis. 2621 5

Previous studies demonstrate that human enterovirus 71 (EV71), a primary causative agent for hand, foot, and mouth disease, activates caspase-3 through the non-structural viral 3C protein to induce host cell apoptosis; however, until now it was unclear how 3C activates caspase-3 and how caspase-3 activation affects viral production. Our results demonstrate that 3C binds caspase-8 and caspase-9 but does not directly bind caspase-3 to activate them, and that the proteolytic activity of 3C is required by the activation of caspase-8, caspase-9, and caspase-3. Inhibition of caspase-3 activity attenuates apoptosis in 3C-transfected cells. Furthermore, caspase-3 inhibitor protects host cells from the cytopathic effect of EV71 infection and prevents cell cycle arrest, which is known to be favored for EV71 viral replication. Inhibition of caspase-3 activity decreases EV71 viral protein expression and viral production, but has no effect on viral entry, replication, even polyprotein translation. Therefore, caspase-3 is exploited functionally by EV71 to facilitate its production, which suggests a novel therapeutic approach for the treatment and prevention of hand, foot, and mouth disease.
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PMID:Caspase-3 Inhibition Attenuates the Cytopathic Effects of EV71 Infection. 2975 38

Enterovirus A71 (EV-A71) is one of the causative agents causing the hand-foot-mouth disease which associated with fatal neurological complications. Several sporadic outbreaks of EV-A71 infections have been recently reported from Asia-Pacific regions and potentially established endemicity in the area. Currently, there is no effective vaccine or antiviral drug for EV-A71 available. This may be attributable to the limited information about its pathogenesis. In this study, the recombinant nonstructural 2B protein of EV-A71 was successfully produced in human neuroblastoma SH-SY5Y cells and evaluated for its effects on induction of the cell apoptosis and the pathway involved. The EV-A71 2B-transfected SH-SY5Y cells showed significantly higher difference in the cell growth inhibition than the mock and the irrelevant protein controls. The transfected SH-SY5Y cells underwent apoptosis and showed the significant upregulation of caspase-9 (CASP9) and caspase-12 (CASP12) genes at 3- and 24-h post-transfection, respectively. Interestingly, the level of cytosolic Ca2+ was significantly elevated in the transfected SH-SY5Y cells at 6- and 12-h post-transfection. The caspase-9 is activated by mitochondrial signaling pathway while the caspase-12 is activated by ER signaling pathway. The results suggested that EV-A71 2B protein triggered transient increase of the cytosolic Ca2+ level and associated with ER-mitochondrial interactions that drive the caspase-dependent apoptosis pathways. The detailed mechanisms warrant further studies for understanding the implication of EV-A71 infection in neuropathogenesis. The gained knowledge is essential for the development of the effective therapeutics and antiviral drugs.
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PMID:A nonstructural 2B protein of enterovirus A71 increases cytosolic Ca2+ and induces apoptosis in human neuroblastoma SH-SY5Y cells. 3193 92