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 Cells1

Abstract

Acute H(2)O(2) exposure to placental artery endothelial cells induced an array of tyrosine-phosphorylated proteins, including caveolin 1 (CAV1) rapid and transient tyr(14) phosphorylated in a time- and concentration-dependent manner. Basal tyr(14) 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 H(2)O(2). Treatment with H(2)O(2) 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 H(2)O(2)-induced CAV1 phosphorylation in a concentration-dependent manner. Acute treatment with H(2)O(2) activated multiple signaling pathways, including the mitogen-activated protein kinases (MAPK) members (MAPK3/1-ERK2/1, MAPK8/9-JNK1/2, and MAPK11-p38(mapk)) and the c-src tyrosine kinase (CSK). Pharmacological studies demonstrated that, among these pathways, only the blockade of CSK activation abolished H(2)O(2)-induced CAV1 phosphorylation. Additionally, H(2)O(2)-induced CAV1 phosphorylation was reversible rapidly (<10 min) upon H(2)O(2) 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.

Dispensability and dynamics of caveolin-1 during liver regeneration and in isolated hepatic cells

“…38 Our results show that liver regeneration after PH causes some Cav-1 phosphorylation, and the phosphorylated protein is located in cytosolic domains.…”

Caveolin-1 as a potential high-risk prostate cancer biomarker

“…The relationship of caveolin-1 with oxidative stress can also be viewed from another point of view. Recent studies have demonstrated that caveolin-1 is a target molecule in p38 MAPK mediated response to stress conditions such as oxidative stress (27,28). After such stimuli, caveolin-1 is phosphorylated and thus contributes to various signalling pathways (60) resulting most likely in processes, such as premature cellular senescence (27).…”

“…Changes in protein function lead to the lapse of cell functions (adhesion) and cell mobility and the development of metastatic processes (22). Furthermore, it has been demonstrated that caveolin-1 expression is induced under stress conditions, such as oxidative stress (27,28).…”

TRPC1 binds to caveolin-3 and is regulated by Src kinase – role in Duchenne muscular dystrophy

“…Members of the Src-kinase family can phosphorylate TRPC3 (Kawasaki et al, 2006) and TRPC6 (Hisatsune et al, 2004); however, regulation of TRPC1 activity by Src has not been investigated. Src kinase has been shown to be activated by reactive oxygen species (ROS), such as hydrogen peroxide (H 2 O 2 ) (Chen et al, 2005), and TRPC3 activity is increased by ROS (Poteser et al, 2006). Thus, it is possible that ROS-induced Src activation, leads to phosphorylation and activation of transient receptor potential canonical (TRPC) channels.…”