Phosphatase PTEN is inactivated in bovine aortic endothelial cells exposed to cyclic strain.
Hemodynamic forces, including cyclic strain (CS) and shear stress (SS), have been recognized as important modulators of vascular cell morphology and function. PTEN (also known as MMAC1/TEP1) is a lipid phosphatase that leads to a decrease in intracellular phosphatidylinositol 3,4,5 trisphosphate (PIP3) and therefore can modulate the stimulating effect of phosphatidylinositol 3-kinase (PI3K). In this study, we focused on the upstream regulators of the PI3K-Akt pathway by assessing Akt, PTEN, casein kinase 2 (CK2) (a kinase that catalyzes phosphorylation of PTEN), and PI3K activity in endothelial cells (EC) exposed to CS. The activity of phospho-PTEN (n = 4) and phospho-CK2 (n = 4) increased in a time-dependent fashion, reaching maximal activity by 10 min of CS stimulation. The peak of phospho-Akt activity (n = 4) occurred later, at 60 min. Akt activity was altered by transfection of EC with dominant negative PTEN plasmids. Furthermore, CS increased PIP3 immunoreactivity in a time-dependent manner, reaching maximal activity after 60 min of CS stimulation, and these effects were affected by transfection of EC with dominant negative PTEN plasmids. Inhibition of PTEN activity had no effect on CS-mediated cell proliferation but inhibited CS-mediated suppression of apoptosis.
Hoshino
Yuji
Y
Department of Surgery, Section of Vascular Surgery, Yale University School of Medicine and Veterans Administration Health Care System, New Haven, Connecticut 06520, USA.
Nishimura
Kengo
K
Sumpio
Bauer E
BE
D000818:Animals; D001011:Aorta / Q000166:cytology*; D047390:Casein Kinase II / Q000378:metabolism; D002417:Cattle; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000201:enzymology*; D004789:Enzyme Activation; D007150:Immunohistochemistry; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013314:Stress, Mechanical
D018129:Phosphatidylinositol Phosphates; C060974:phosphatidylinositol 3,4,5-triphosphate; D047390:Casein Kinase II; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase