Signal transduction mechanisms of arginase induction by IL-4, IL-13 and basic FGF in bovine coronary artery endothelial cells : a dissertation /
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| Format: | Thesis Book |
| Language: | English |
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[College Station, Tex.] :
[Texas A&M University System Health Science Center],
[2004]
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| Abstract: | ABSTRACT: Arginase is the enzyme hydrolyzing L-arginine to urea and L-ornithine, which can be converted to polyamines. Polyamines are important molecules for inflammation since they promote cell growth and tissue repair. However, very few data have been published on the underlying mechanisms regulating arginase activity and protein expression. To address this issue, I explored the effect of cytokines interleukin 4 (IL-4) and interleukin 13 (IL-13) and a growth factor basic fibroblast growth factor (bFGF) on arginase and the signal transduction pathways activated by IL-4, IL-13 and bFGF leading to arginase induction in bovine coronary artery endothelial cells (bCAEC) because vascular endothelial cells as well as lymphocytes play critical roles during the inflammatory process. In the present study, I found that IL-4 and IL-13 induced arginase activity as well as cytosolic phospholipase A2 (cPLA2) activity and prostaglandin I₂ (PGI₂) synthesis in bCAEC. IL-4 or IL-13 induced arginase activity was suppressed by inhibitors of cPLA2 (AACOCF3), cycooxygenases (indomethacin, SC-560 and NS-398), and protein kinase A (PKA) (H89 and KT5720). In addition, PGI2 and cAMP also induced arginase. Taken together, these results suggest that IL-4 and IL-13 induced arginase, and the arginase induction was mediated by cPLA2, cyclooxygenases, PGI2, cAMP and PKA in the vascular endothelial cells. I also found that bFGF and overexpression of Ras protein induced arginase activity in bCAEC. bFGF-induced arginase activity was abolished by cycloheximide, and attenuated by inhibitors of receptor tyrosine kinases (genistein), MEK1 (PD98059) and phosphoinositide 3-kinase (PI3K) wortmannin). In addition, inhibition of arginase with L-norvaline reduced by bCAEC proliferation. Taken together, these results suggest that bFGF induces arginase through receptor tyrosine kinase-Ras-Raf/MEK1/MAPK and/or receptor tyrosine kinase-PI3K pathways in bCAEC, and that arginase activity is important for the endothelial cell proliferation. |
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| Item Description: | Vita. "Major Subject: Medical Sciences". "Submitted to the Office of Graduate Studies of Texas A&M University System Health Science Center in partial fulfillment for the requirements for the degree of Doctor of Philosophy May 2004." Approved as to style and content by: Lih Kuo, Reza Forough, Rajesh Miranda, Emily Wilson, Harris J. Granger. |
| Physical Description: | vii, 72 leaves : illustrations ; 28 cm. |
| Bibliography: | Includes bibliographical references (leaves 57-71). |