Articles tagués AKT

The transcription factor Eya2 prevents pressure overload-induced adverse cardiac remodeling

The transcription factor Eya2 prevents pressure overload-induced adverse cardiac remodeling

Seung Hee Lee, Dong Kwon Yang, Bo Youn Choi, Young-Hoon Lee, Seon-Young Kim, Dongtak Jeong, Roger J. Hajjar, Woo Jin Park

Journal of Molecular and Cellular Cardiology, Volume 46, Issue 4, April 2009, Pages 596-605, ISSN 0022-2828, doi: 10.1016/j.yjmcc.2008.12.021

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Development of a novel mouse glioma model using lentiviral vectors

Development of a novel mouse glioma model using lentiviral vectors

Tomotoshi Marumoto, Ayumu Tashiro, Dinorah Friedmann-Morvinski, Miriam Scadeng, Yasushi Soda, Fred H Gage & Inder M Verma

Nature Medicine Published online: 4 January 2009 | doi:10.1038/nm.1863

Eh oui ! Il y en a qui devraient lire 😉

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Opposite Effects of Notch-1 and Notch-2 on Mesothelioma Cell Survival under Hypoxia Are Exerted through the Akt Pathway

Opposite Effects of Notch-1 and Notch-2 on Mesothelioma Cell Survival under Hypoxia Are Exerted through the Akt Pathway

Irene Graziani, Sandra Eliasz, Melissa A. De Marco, Yuanbin Chen, Harvey I. Pass, Richard M. De May, Peter R. Strack, Lucio Miele and Maurizio Bocchetta

Cancer Research 68, 9678-9685, December 1, 2008. doi:10.1158/0008-5472.CAN-08-0969

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Vascular Endothelial Growth Factor Up-regulates ICAM-1 Expression

Vascular Endothelial Growth Factor Up-regulates ICAM-1 Expression via the Phosphatidylinositol 3 OH-kinase/AKT/Nitric Oxide Pathway and Modulates Migration of Brain Microvascular Endothelial Cells

Zivotije Radisavljevic, Hava Avraham, and Shalom Avraham

THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 275, No. 27, Issue of July 7, pp. 20770 –20774, 2000

Endothelium of the cerebral blood microvessels, which constitutes the major component of the blood-brain barrier, controls leukocyte and metastatic cancer cell adhesion and trafficking into the brain parenchyma. In this study, using rat primary brain microvascular endothelial cells (BMEC), we demonstrate that the vascular endothelial growth factor (VEGF), a potent promoter of angiogenesis, up-regulates the expression of the intracellular adhesion molecule-1 (ICAM-1) through a novel pathway that includes phosphatidylinositol 3 OH-kinase (PI3K), AKT, and nitric oxide (NO), resulting in the migration of BMEC. Upon VEGF treatment, AKT is phosphorylated in a PI3K-dependent manner. AKT activation leads to NO production and release and activation-deficient AKT attenuates NO production stimulated by VEGF. Transfection of the constitutive myr-AKT construct significantly increased basal NO release in BMEC. In these cells, VEGF and the endothelium-derived NO synergistically up-regulated the expression of ICAM-1, which was mediated by the PI3K pathway. This activity was blocked by the PI3K-specific inhibitor, wortmannin. Furthermore, VEGF and NO significantly increased BMEC migration, which was mediated by the up-regulation of ICAM-1 expression and was dependent on the integrity of the PI3K/AKT/NO pathway. This effect was abolished by wortmannin, by the specific ICAM-1 antibody, by the specific inhibitor of NO synthase, NG-L-monomethyl-arginine (L-NMMA) or by a combination of wortmannin, ICAM-1 antibody, and L-NMMA. These findings demonstrate that the angiogenic factor VEGF up-regulates ICAM-1 expression and signals to ICAM-1 as an effector molecule through the PI3K/AKT/NO pathway, which leads to brain microvessel endothelial cell migration. These observations may contribute to a better understanding of BMEC angiogenesis and the physiological as well as pathophysiological function of the blood-brain barrier, whose integrity is crucial for normal brain function.

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