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1 October 2005 Tyrosine Phosphorylation of Caveolin 1 by Oxidative Stress Is Reversible and Dependent on the c-src Tyrosine Kinase but Not Mitogen-Activated Protein Kinase Pathways in Placental Artery Endothelial Cells
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Abstract

Acute H2O2 exposure to placental artery endothelial cells induced an array of tyrosine-phosphorylated proteins, including caveolin 1 (CAV1) rapid and transient tyr14 phosphorylated in a time- and concentration-dependent manner. Basal tyr14 phosphorylated CAV1 was primarily located at the edges of cells and associated with actin filaments. Phosphorylated CAV1 was markedly increased and diffused with the disorganization of actin filaments at 20 min, disappeared at 120 min treatment with 0.2 mM H2O2. Treatment with H2O2 also disorganized actin filaments and changed cell shape in a time-dependent manner. Pretreatment with antioxidants catalase completely, whereas the other tested superoxide dismutase, N-acetyl-l-cysteine and sodium formate partially attenuated H2O2-induced CAV1 phosphorylation in a concentration-dependent manner. Acute treatment with H2O2 activated multiple signaling pathways, including the mitogen-activated protein kinases (MAPK) members (MAPK3/1-ERK2/1, MAPK8/9-JNK1/2, and MAPK11-p38mapk) and the c-src tyrosine kinase (CSK). Pharmacological studies demonstrated that, among these pathways, only the blockade of CSK activation abolished H2O2-induced CAV1 phosphorylation. Additionally, H2O2-induced CAV1 phosphorylation was reversible rapidly (<10 min) upon H2O2 withdrawal. Because maternal and fetal endothelia must make dynamic adaptations to oxidative stress resulting from enhanced pregnancy-specific oxygen metabolism favoring prooxidant production, which is emerging as one of the leading causes of the dysfunctional activated endothelium during pregnancy, these unique features of CAV1 phosphorylation on oxidative stress observed implicate an important role of CAV1 in placental endothelial cell biology during pregnancy.

Dong-bao Chen, Su-min Li, Xiao-Xian Qian, ChongSoo Moon, and Jing Zheng "Tyrosine Phosphorylation of Caveolin 1 by Oxidative Stress Is Reversible and Dependent on the c-src Tyrosine Kinase but Not Mitogen-Activated Protein Kinase Pathways in Placental Artery Endothelial Cells," Biology of Reproduction 73(4), 761-772, (1 October 2005). https://doi.org/10.1095/biolreprod.105.040881
Received: 11 February 2005; Accepted: 1 June 2005; Published: 1 October 2005
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