Premium
TRPC‐1 knockdown abrogates nuclear factor‐kB‐dependent anti‐apoptotic gene expression induced by thrombin in endothelial cells
Author(s) -
Thippegowda Prabhakar Bettadathunga,
Tiruppathi Chinnaswamy,
Xue Jiaping,
Sundivakkam Premanand,
Singh Vandna,
Malik Asrar B
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.830.3
Subject(s) - thrombin , gene knockdown , trpc , microbiology and biotechnology , chemistry , interleukin 8 , signal transduction , apoptosis , biology , receptor , cytokine , immunology , biochemistry , transient receptor potential channel , platelet
Thrombin activation of protease‐activated receptor‐1 induces Ca2+ influx through store‐operated Ca2+ entry channels (SOC) in endothelial cells. Previously we have shown that the canonical TRPC isoform TRPC1 is an essential component of SOC in endothelial cells. Further, we showed that thrombin‐induced Ca2+ influx signal activates nuclear factor‐kB (NF‐kB) in endothelial cells. In this study we measured thrombin‐induced expression of NF‐kB regulated genes in human pulmonary artery endothelial cells (ECs) utilizing Gene Microarray. Thrombin stimulation increased at least sixteen genes between 5‐ and 20‐fold over basal in ECs. Thrombin‐induced expression of anti‐apoptotic genes such as A20, IL8, and BCL3 were markedly reduced by pharmacological inhibition of Ca2+ influx in ECs. TRPC1 knockdown with siRNA abolished thrombin‐induced Ca2+ influx and markedly reduced A20, IL8, and BCL3 expression in ECs. Thus our results suggest that Ca2+ influx via SOC activates NF‐kB signaling to induce expression of A20, IL8, and BCL3 to promote cytoprotective effect in endothelial cells.