Abstract
Bcl-2 is an intracellular membrane-associated protein that functions to block programmed cell death. Despite recurrent exposure to cellular toxins from the circulation and tissue, endothelial cells are remarkably resistant to cell death. Because Bcl-2 protein levels are low or undetectable in endothelial cells, we postulated that other members of the growing Bcl-2 family would be present in endothelial cells to provide protection against apoptosis. Degenerate primers to two conserved regions of the Bcl-2 family were used to amplify potential homologues in endothelial cells. This strategy resulted in the isolation of a human Bcl-2 homologue related to murine Al, a recently identified member of this family. We show here that, in endothelial cells, human Al is rapidly inducible by phorbol ester and the inflammatory cytokines, tumor necrosis factor-alpha and interleukin-1beta, but not by the growth factors, basic fibroblast growth factor or vascular endothelial growth factor. Al is the only known Bcl-2 family member that is inducible by inflammatory cytokines, suggesting that it may play a protective role during inflammation. Additionally, vascular smooth muscle cells and various nonhematopoietic tissues express human Al, indicating that human Al is a widely expressed Bcl-2 homologue.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Apoptosis
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Base Sequence
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Cloning, Molecular
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Cytokines / pharmacology
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DNA, Complementary / genetics
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / genetics*
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Endothelial Growth Factors / pharmacology*
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Endothelium, Vascular / cytology
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / metabolism
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Fibroblast Growth Factor 2 / pharmacology*
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Gene Expression Regulation / drug effects*
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Genes*
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Homeodomain Proteins*
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Humans
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Inflammation / metabolism
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Lymphokines / pharmacology*
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Minor Histocompatibility Antigens
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Molecular Sequence Data
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Multigene Family
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Polymerase Chain Reaction
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins c-bcl-2
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Replication Protein C
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Repressor Proteins*
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Saccharomyces cerevisiae Proteins*
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Sequence Alignment
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Sequence Homology, Amino Acid
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Species Specificity
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Tetradecanoylphorbol Acetate / pharmacology
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Umbilical Veins
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
Substances
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BCL2-related protein A1
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Cytokines
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DNA, Complementary
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DNA-Binding Proteins
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Endothelial Growth Factors
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Homeodomain Proteins
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Lymphokines
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MATA1 protein, S cerevisiae
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Minor Histocompatibility Antigens
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Repressor Proteins
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Saccharomyces cerevisiae Proteins
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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Fibroblast Growth Factor 2
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Replication Protein C
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Tetradecanoylphorbol Acetate