Molecular determinants for cellular uptake of Tat protein of human immunodeficiency virus type 1 in brain cells.
AUTOR(ES)
Ma, M
RESUMO
We measured the cellular uptake of 125I-labeled full-length Tat (amino acids 1 to 86) (125I-Tat(1-86)) and 125I-Tat(1-72) (first exon) in human fetal astrocytes, neuroblastoma cells, and human fetal neurons and demonstrated that the uptake of 125I-Tat(1-72) without the second exon was much lower than that of 125I-Tat(1-86) (P < 0.01). This suggests an important role for the C-terminal region of Tat for its cellular uptake. 125I-Tat uptake could be inhibited by dextran sulfate and competitively inhibited by unlabeled Tat but not by overlapping 15-mer peptides, suggesting that Tat internalization is charge and conformationally dependent. Interestingly, one of 15-mer peptides, Tat(28-42), greatly enhanced 125I-Tat uptake. These findings are important for understanding the neuropathogenesis of human immunodeficiency virus type 1 infection and in the potential application of Tat for drug delivery to cells.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=191362Documentos Relacionados
- Tat protein of human immunodeficiency virus type 1 represses expression of manganese superoxide dismutase in HeLa cells.
- Human immunodeficiency virus type 1 Tat upregulates interleukin-2 secretion in activated T cells.
- Diazepam-mediated inhibition of human immunodeficiency virus type 1 expression in human brain cells.
- Potentiation of human immunodeficiency virus type 1 Tat by human cellular proteins.
- Trans-activation of the JC virus late promoter by the tat protein of type 1 human immunodeficiency virus in glial cells.