Attenuation of endothelin-1-induced PKB and ERK1/2 signaling, as well as Egr-1 expression, by curcumin in A-10 vascular smooth muscle cells.
Endothelin-1 (ET-1) is implicated in the pathogenesis of vascular abnormalities through the hyperactivation of growth promoting pathways, including protein kinase B (PKB) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. ET-1 has been shown to elicit its responses through the generation of reactive oxygen species (ROS). Curcumin, the main constituent of the spice turmeric, exhibits cardio-protective, anti-proliferative, and antioxidant properties; however, the precise molecular mechanism of its action is unclear. Therefore, in the present study, we investigated the effects of curcumin on ET-1-induced PKB and ERK1/2 signaling, as well as insulin-like growth factor type receptor (IGF-1R) phosphorylation. Curcumin dose-dependently inhibited ET-1-induced phosphorylation of PKB, ERK1/2, c-Raf, and insulin-like growth factor type 1 receptor (IGF-1R), in vascular smooth muscle cells (VSMC). Furthermore, curcumin also attenuated ET-1-induced expression of early growth response (Egr)-1, a transcription factor downstream of ERK1/2 that plays a regulatory role in several cardiovascular pathological processes. In conclusion, these data demonstrate that curcumin is a potent inhibitor of ET-1-induced mitogenic and proliferative signaling events in VSMC and suggest that the ability of curcumin to attenuate these events may contribute as a potential mechanism for its cardiovascular protective response.
Laboratory of Cell Signaling, Research Center of Centre Hospitalier de l'Université de Montréal - Angus Campus, Department of Medicine, Université de Montréal, QC, Canada.
Georgia
G
Kapakos
Viktoria
V
Youreva
Ashok K
AK
Srivastava
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology; D017209:Apoptosis / Q000187:drug effects; D018929:Cell Culture Techniques; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D015536:Down-Regulation; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis*; D019332:Endothelin-1 / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000196:embryology / Q000201:enzymology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats
D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D019332:Endothelin-1; D051057:Proto-Oncogene Proteins c-akt; D003474:Curcumin