Immunohistochemical localization of the amino acid transporter SNAT2 in the rat brain.

SNAT2 is a neutral amino acid carrier that belongs to the system A family. Since its function in the nervous system remains unclear, we have analyzed its distribution in the rat CNS using specific antisera. Although SNAT2 is expressed widely in the CNS, it is enriched in the spinal cord and the brainstem nuclei, especially those of the auditory system. At the cellular level, SNAT2 was preferentially located in neuronal cell bodies and processes, although it was also strongly expressed in the meninges and ependyma. In astrocytes, the localization of SNAT2 was more restricted since it was intensely expressed in the perivascular end-feet, glia limitans, cerebellar astrocytes and Bergmann glia, but it was less intense in astrocytes of the cerebral parenchyma. Among neurons, the primary sensory neurons of the mesencephalic trigeminal nucleus appeared to be those that most strongly express SNAT2, but many other neurons, including cortical pyramidal cells and their dendrites were also intensely stained. In several regions the transporter was detected in axons, especially in the brainstem, and its presence in both dendrites and axons was confirmed by confocal microscopy and ultrastructural studies. However, while SNAT2 was observed in the large principal dendrites and the small distal dendrites, it was only found in axonal shafts and was excluded from terminals. Some glutamatergic neurons were among the more intensely labeled cells whereas SNAT2 was not detected on GABAergic neurons. The expression of SNAT2 partially coincides with that reported for SNAT1, especially in glutamatergic neurons. Hence, both proteins could fulfill complementary roles in replenishing glutamate pools and be differentially regulated under different physiological conditions. They also seem to co-localize in non-neuronal cells probably contributing to amino acid fluxes through the blood-brain barrier.

African swine fever virus IAP homologue inhibits caspase activation and promotes cell survival in mammalian cells.

African swine fever virus (ASFV) A224L is a member of the inhibitor of apoptosis protein (IAP) family. We have investigated the antiapoptotic function of the viral IAP both in stably transfected cells and in ASFV-infected cells. A224L was able to substantially inhibit caspase activity and cell death induced by treatment with tumor necrosis factor alpha and cycloheximide or staurosporine when overexpressed in Vero cells by gene transfection. We have also observed that ASFV infection induces caspase activation and apoptosis in Vero cells. Furthermore, using a deletion mutant of ASFV lacking the A224L gene, we have shown that the viral IAP modulates the proteolytic processing of the effector cell death protease caspase-3 and the apoptosis which are induced in the infected cells. Our findings indicate that A224L interacts with the proteolytic fragment of caspase-3 and inhibits the activity of this protease during ASFV infection. These observations could indicate a conserved mechanism of action for ASFV IAP and other IAP family members to suppress apoptosis.