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This Article Full Text Full Text (PDF) All Versions of this Article: 73/4/761    most recent biolreprod.105.040881v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Chen, D.-b. Articles by Zheng, J. Search for Related Content PubMed PubMed Citation Articles by Chen, D.-b. Articles by Zheng, J. Agricola Articles by Chen, D.-b. Articles by Zheng, J.

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

Department of Reproductive Medicine,⁵ University of California San Diego, La Jolla, California 92093 Perinatal Research Laboratories,⁶ Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, WI 53715

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-p38^mapk) 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.

caveolin 1, kinases, oxidative stress, placenta, placental artery endothelial cells, pregnancy, signal transduction, stress, tyrosine phosphorylation

² Correspondence: Dong-bao Chen, Division of Maternal-Fetal Medicine (MC0802), Department of Reproductive Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0802. FAX: 619 543 2919; dochen{at}ucsd.edu

³ Current address: The Third Affiliated Hospital, Sun Yat-sen University, Guangdong 510630, P.R. China

⁴ Current address: Department of Obstetrics and Gynecology, Kangdong Sacred Heart Hospital, Hallym University, Seoul 134-701, Korea