Gene interactions and pathways from curated databases and text-mining
Arterioscler Thromb Vasc Biol 2004, PMID: 14962944

Involvement of neuron-derived orphan receptor-1 (NOR-1) in LDL-induced mitogenic stimulus in vascular smooth muscle cells: role of CREB.

Rius, Jordi; Martínez-González, José; Crespo, Javier; Badimon, Lina

OBJECTIVE

Low density lipoproteins (LDLs) modulate the expression of key genes involved in atherogenesis. Recently, we have shown that the transcription factor neuron-derived orphan receptor-1 (NOR-1) is involved in vascular smooth muscle cell (VSMC) proliferation. Our aim was to analyze whether NOR-1 is involved in LDL-induced mitogenic effects in VSMC.

RESULTS

LDL induced NOR-1 expression in a time- and dose-dependent manner. Antisense oligonucleotides against NOR-1 inhibit DNA synthesis induced by LDL in VSMCs as efficiently as antisense against the protooncogene c-fos. The upregulation of NOR-1 mRNA levels by LDL involves pertusis-sensitive G protein-coupled receptors, Ca2+ mobilization, protein kinases A (PKA) and C (PKC) activation, and mitogen-activated protein kinase pathways (MAPK) (p44/p42 and p38). LDL promotes cAMP response element binding protein (CREB) activation (phosphorylation in Ser133). In transfection assays a dominant-negative of CREB inhibits NOR-1 promoter activity, while mutation of specific (cAMP response element) CRE sites in the NOR-1 promoter abolishes LDL-induced NOR-1 promoter activity.

CONCLUSIONS

In VSMCs, LDL-induced mitogenesis involves NOR-1 upregulation through a CREB-dependent mechanism. CREB could play a role in the modulation by LDL of key genes (containing CRE sites) involved in atherogenesis.

Diseases/Pathways annotated by Medline MESH: Calcium Signaling, MAP Kinase Signaling System
Document information provided by NCBI PubMed

Text Mining Data

protein kinases A (PKA) → p44/p42: " The upregulation of NOR-1 mRNA levels by LDL involves pertusis-sensitive G protein coupled receptors, Ca2+ mobilization, protein kinases A (PKA) and C ( PKC ) activation , and mitogen activated protein kinase pathways ( MAPK ) ( p44/p42 and p38 ) "

protein kinases A (PKA) → p44/p42: " The upregulation of NOR-1 mRNA levels by LDL involves pertusis-sensitive G protein coupled receptors, Ca2+ mobilization, protein kinases A (PKA) and C ( PKC ) activation , and mitogen activated protein kinase pathways ( MAPK ) ( p44/p42 and p38 ) "

protein kinases A (PKA) → p38: " The upregulation of NOR-1 mRNA levels by LDL involves pertusis-sensitive G protein coupled receptors, Ca2+ mobilization, protein kinases A (PKA) and C ( PKC ) activation , and mitogen activated protein kinase pathways ( MAPK ) ( p44/p42 and p38 ) "

CREB → LDL: " LDL promotes cAMP response element binding protein ( CREB ) activation ( phosphorylation in Ser133 ) "

Manually curated Databases

  • OpenBEL Selventa BEL large corpus: CREB1 (increases)
    Evidence: LDL promotes cAMP response element binding protein (CREB) activation (phosphorylation in Ser133). In transfection assays a dominant-negative of CREB inhibits NOR-1 promoter activity, while mutation of specific (cAMP response element) CRE sites in the NOR-1 promoter abolishes LDL-induced NOR-1 promoter activity.
  • OpenBEL Selventa BEL large corpus: CREB1 → CREB1 (directlyIncreases, CREB1 Activity)
    Evidence: LDL promotes cAMP response element binding protein (CREB) activation (phosphorylation in Ser133). In transfection assays a dominant-negative of CREB inhibits NOR-1 promoter activity, while mutation of specific (cAMP response element) CRE sites in the NOR-1 promoter abolishes LDL-induced NOR-1 promoter activity.