RESUMO
The brain is particularly vulnerable to oxygen free radicals, and these radicals have been implicated in the pathology of several neurological disorders. In this study, the modulation of TNF-related apoptosis-inducing ligand (TRAIL) expression by oxidative stress was shown in LN215 cells, an astroglioma cell line. Hydrogen peroxide (H2O2) treatment increased TRAIL expression in LN215 cells and H2O2-induced TRAIL augmented apoptosis in Peer cells, a cell line sensitive to TRAIL- mediated cell death. Our findings suggest that the upregulation of TRAIL in astroglial cells may abrogate immune cell effector functions.
Assuntos
Humanos , Regulação para Cima , Ligante Indutor de Apoptose Relacionado a TNF/biossíntese , Linfócitos T/metabolismo , Ribonucleases/metabolismo , Estresse Oxidativo , Imunossupressores/farmacologia , Peróxido de Hidrogênio/farmacologia , Regulação Neoplásica da Expressão Gênica , Ciclosporina/farmacologia , Linhagem Celular Tumoral , Astrócitos/metabolismo , Apoptose , Hipóxia , Alergia e ImunologiaRESUMO
Significant neurodegeneration leading to neurocognitive disorder and dementia has been observed in the central nervous system (CNS) of patients with HIV infection. Part of the neurodegenerative cascade in AIDS dementia may involve glial cells, perhaps through inhibiting the release of glial factors that protect neurons from variety of insults. Here, in an effort to find the mediators of HIV-induced brain damage, we examined the possible effect of a HIV-1 transmenbrane protein gp41 peptide (583-599) on expression and metabolism of amyloid precursor protein (APP) using human astroglial cell line. RT-PCR analysis demonstrated that gp 41 peptide did not significantly change expression patterns of APP mRNAs in lipopolysaccharide (LPS) activated astroglial cells for 6h. In contrast, gp41 peptide remarkably downregulated the level of secreted from of APP (sAPPa), which has been recently demonstrated as a potent neuroprotective factor. The reverse peptide, used as control had no such effect. The mechanism of gp41 peptide-induced down regulation of sAPPa production appears to be TGF-beta independent. These results implicate that gp41 peptide could be one of the mediator involved in the modulation of APP secretion within CNS, possibly contributing to the neuronal degeneration in HIV-1 associated neurological disease.