TY - JOUR
T1 - Stretch-induced morphological changes of human endothelial cells depend on the intracellular level of Ca2+ rather than of cAMP
AU - Yamada, Takako
AU - Naruse, Keiji
AU - Sokabe, Masahiro
N1 - Funding Information:
We thank Dr. M. Okada for providing umbilical cords. We also thank Ms. M. Takahashi for excellent technical assistance. This work was supported by grants-in aid from the Ministry of Education Science and Culture Japan (KN and MS), a research grant (Research for the Future Program) from the Japan Society for the Promotion of Science (KN and MS), a grant from Japan Space Forum (MS), a grant from CREST (MS), and a grant from the Ministry of Health and Welfare (MS).
PY - 2000/10/13
Y1 - 2000/10/13
N2 - When exposed to a uni-axial cyclic stretch, cultured human umbilical vein endothelial cells (HUVECs) align and elongate perpendicular to the stretch axis. Previous studies showed that forskolin inhibited stretch-induced orientation of endothelial cells, suggesting that adenosine3:5-cyclic monophosphate (cAMP) plays an important role in the shape change. However, we have recently shown that stretch-induced shape changes in cultured HUVECs are due to increased [Ca2+](i). In the present study, we examined the possible role of cAMP in stretch-induced shape changes in cultured HUVECs. Application of uni-axial cyclic stretch induced a gradual rise in cAMP reaching a peak level at 60 min after the onset of stretch. The adenylate cyclase activator, forskolin, increased the basal level of cAMP but inhibited the rise in [Ca2+](i) resulting in no cell shape changes. In contrast, N 6,2-dibutyryladenosine3:5-cyclic monophosphate (dbcAMP) enhanced the stretch-induced increase in cAMP and [Ca2+](i) and resulted in cell shape changes. On the other hand, 2'5'-dideoxyadenosine (DDA), an adenylate cyclase inhibitor, inhibited stretch-induced increases in cAMP and [Ca2+](i) resulting in no cell shape changes. In summary, our data showed that cell shape changes were consistently dependent on [Ca2+](i) rather than cAMP levels. We conclude that the primary second messenger in the stretch-induced shape changes in HUVECs is intracellular Ca2+ rather than cAMP. (C) 2000 Elsevier Science Inc.
AB - When exposed to a uni-axial cyclic stretch, cultured human umbilical vein endothelial cells (HUVECs) align and elongate perpendicular to the stretch axis. Previous studies showed that forskolin inhibited stretch-induced orientation of endothelial cells, suggesting that adenosine3:5-cyclic monophosphate (cAMP) plays an important role in the shape change. However, we have recently shown that stretch-induced shape changes in cultured HUVECs are due to increased [Ca2+](i). In the present study, we examined the possible role of cAMP in stretch-induced shape changes in cultured HUVECs. Application of uni-axial cyclic stretch induced a gradual rise in cAMP reaching a peak level at 60 min after the onset of stretch. The adenylate cyclase activator, forskolin, increased the basal level of cAMP but inhibited the rise in [Ca2+](i) resulting in no cell shape changes. In contrast, N 6,2-dibutyryladenosine3:5-cyclic monophosphate (dbcAMP) enhanced the stretch-induced increase in cAMP and [Ca2+](i) and resulted in cell shape changes. On the other hand, 2'5'-dideoxyadenosine (DDA), an adenylate cyclase inhibitor, inhibited stretch-induced increases in cAMP and [Ca2+](i) resulting in no cell shape changes. In summary, our data showed that cell shape changes were consistently dependent on [Ca2+](i) rather than cAMP levels. We conclude that the primary second messenger in the stretch-induced shape changes in HUVECs is intracellular Ca2+ rather than cAMP. (C) 2000 Elsevier Science Inc.
KW - DDA
KW - Forskolin
KW - Stretch-activated channel
KW - Uni-axial cyclic stretch
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U2 - 10.1016/S0024-3205(00)00844-4
DO - 10.1016/S0024-3205(00)00844-4
M3 - Article
C2 - 11104362
AN - SCOPUS:0034644755
VL - 67
SP - 2605
EP - 2613
JO - Life Sciences
JF - Life Sciences
SN - 0024-3205
IS - 21
ER -