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Shear stress activates extracellular signal‐regulated kinase 1/2 via the angiotensin II type 1 receptor
Author(s) -
Ramkhelawon Bhama,
Rivas Daniel,
Lehoux Stephanie
Publication year - 2013
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/fj.12-222299
Subject(s) - angiotensin ii , losartan , microbiology and biotechnology , angiotensin ii receptor type 1 , nadph oxidase , shear stress , chemistry , colocalization , extracellular , receptor , biophysics , medicine , endocrinology , biology , reactive oxygen species , biochemistry , materials science , composite material
Mechanical factors such as strain, pressure, and shear stress are key regulators of cell function, but the molecular mechanisms underlying the detection and responses to such stimuli are poorly understood. Whether the angiotensin II (AngII) AT1 receptor (AT1R) transduces shear stress in endothelial cells (ECs) is unknown. We exposed human umbilical cord endothelial cells (HUVECs) to a shear stress of 0 (control) or 15 dyn/cm 2 for 5 or 10 min. The colocalization of AT1R with caveolin‐1 (Cav1), endosomal markers Rab5, EEA1, and Rab7, and lysosomal marker Lamp‐1 increased in shear stimulated cells, detected by immunocytochemistry. Shear stress reduced labeling of wild‐type mouse ECs (18±3% of unsheared control, P <0.01) but not Cav1 ‐/‐ ECs (90±10%) with fluorescent AngII, confirming that internalization of AT1R requires Cav1. Shear stress activated ERK1/2 2‐fold ( P <0.01), which was prevented by the AT1R blocker losartan. NADPH oxidase inhibition with apocynin prevented both the colocalization of AT1R with Cav1 and the induction of ERK1/2 by shear stress. Moreover, shear‐dependent ERK1/2 activation was minimal in CHO cells expressing an AT1Ra mutant that does not internalize, compared with cells expressing wild‐type AT1Ra ( P <0.05). Hence, AT1R may be an important transducer of shear stress‐dependent activation of ERK1/2.—Ramkhelawon, B., Rivas, D., Lehoux, S., Shear stress activates extracellular signal‐regulated kinase 1/2 via the angiotensin II type 1 receptor. FASEB J. 27, 3008–3016 (2013). www.fasebj.org