Thioredoxin reductase regulates angiogenesis by increasing endothelial cell-derived vascular endothelial growth factor. 2004

Katie L Streicher, and Matthew J Sylte, and Sally E Johnson, and Lorraine M Sordillo
Department of Veterinary Science, Pennsylvania State University, University Park, 16802, USA.

Low selenium (Se) status increases angiogenesis by inducing the production of vascular endothelial growth factor (VEGF); however, the mechanism responsible for VEGF up-regulation has yet to be characterized. Se's ability to control cellular oxidative state through its incorporation into selenoproteins such as thioredoxin reductase (TrxR) may explain previous studies that connect Se status to tumor angiogenesis. Therefore, the focus of this study was to determine if altered VEGF expression and angiogenesis due to decreased Se levels are influenced by reduced TrxR activity. We found that chemical inhibition of TrxR in Se-sufficient endothelial cells (ECs) was associated with increases in VEGF and VEGF receptor expression, cell migration, proliferation, and angiogenesis to levels similar to those seen in Se-deficient ECs. Specific inhibition of glutathione peroxidase did not affect pro-angiogenic responses, indicating a unique role of the TrxR system during low Se status. These data correlate changes in TrxR activity with changes in VEGF expression and angiogenic development in ECs, which is significant because minimal mechanistic data exist that explain the role of Se in cancer prevention. Understanding the importance of the tumor microenvironment in contributing to angiogenic regulation has the potential to significantly impact breast cancer chemoprevention strategies by focusing on maintaining proper EC function within the mammary gland.

UI MeSH Term Description Entries
D002417 Cattle Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor. Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D002465 Cell Movement The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell. Cell Migration,Locomotion, Cell,Migration, Cell,Motility, Cell,Movement, Cell,Cell Locomotion,Cell Motility,Cell Movements,Movements, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005979 Glutathione Peroxidase An enzyme catalyzing the oxidation of 2 moles of GLUTATHIONE in the presence of HYDROGEN PEROXIDE to yield oxidized glutathione and water. Cytosolic Glutathione Peroxidase,Glutathione Lipoperoxidase,Selenoglutathione Peroxidase,Glutathione Peroxidase, Cytosolic,Lipoperoxidase, Glutathione,Peroxidase, Glutathione,Peroxidase, Selenoglutathione
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D012643 Selenium An element with the atomic symbol Se, atomic number 34, and atomic weight 78.97. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of GLUTATHIONE PEROXIDASE. Selenium-80,Selenium 80
D013880 Thioredoxin-Disulfide Reductase A FLAVOPROTEIN enzyme that catalyzes the oxidation of THIOREDOXINS to thioredoxin disulfide in the presence of NADP+. It was formerly listed as EC 1.6.4.5 Thioredoxin Reductase (NADPH),NADP-Thioredoxin Reductase,NADPH-Thioredoxin Reductase,Thioredoxin Reductase,NADP Thioredoxin Reductase,NADPH Thioredoxin Reductase,Reductase, NADP-Thioredoxin,Reductase, NADPH-Thioredoxin,Reductase, Thioredoxin,Reductase, Thioredoxin-Disulfide,Thioredoxin Disulfide Reductase
D042461 Vascular Endothelial Growth Factor A The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as "tumor angiogenesis factor" and "vascular permeability factor". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced. Vascular Endothelial Growth Factor,Vascular Endothelial Growth Factor-A,GD-VEGF,Glioma-Derived Vascular Endothelial Cell Growth Factor,VEGF,VEGF-A,Vascular Permeability Factor,Vasculotropin,Glioma Derived Vascular Endothelial Cell Growth Factor,Permeability Factor, Vascular
D042783 Endothelial Cells Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer. Capillary Endothelial Cells,Lymphatic Endothelial Cells,Vascular Endothelial Cells,Capillary Endothelial Cell,Cell, Capillary Endothelial,Cell, Endothelial,Cell, Lymphatic Endothelial,Cell, Vascular Endothelial,Cells, Capillary Endothelial,Cells, Endothelial,Cells, Lymphatic Endothelial,Cells, Vascular Endothelial,Endothelial Cell,Endothelial Cell, Capillary,Endothelial Cell, Lymphatic,Endothelial Cell, Vascular,Endothelial Cells, Capillary,Endothelial Cells, Lymphatic,Endothelial Cells, Vascular,Lymphatic Endothelial Cell,Vascular Endothelial Cell

Related Publications

Katie L Streicher, and Matthew J Sylte, and Sally E Johnson, and Lorraine M Sordillo
April 2000, British journal of cancer,
Katie L Streicher, and Matthew J Sylte, and Sally E Johnson, and Lorraine M Sordillo
January 2013, Cell metabolism,
Katie L Streicher, and Matthew J Sylte, and Sally E Johnson, and Lorraine M Sordillo
May 2004, Annals of surgical oncology,
Katie L Streicher, and Matthew J Sylte, and Sally E Johnson, and Lorraine M Sordillo
September 2008, European journal of cancer (Oxford, England : 1990),
Katie L Streicher, and Matthew J Sylte, and Sally E Johnson, and Lorraine M Sordillo
December 1996, The American journal of pathology,
Katie L Streicher, and Matthew J Sylte, and Sally E Johnson, and Lorraine M Sordillo
January 1985, Journal of cellular biochemistry,
Katie L Streicher, and Matthew J Sylte, and Sally E Johnson, and Lorraine M Sordillo
March 2000, Microvascular research,
Katie L Streicher, and Matthew J Sylte, and Sally E Johnson, and Lorraine M Sordillo
January 2016, PloS one,
Katie L Streicher, and Matthew J Sylte, and Sally E Johnson, and Lorraine M Sordillo
December 2004, Pharmacological reviews,
Katie L Streicher, and Matthew J Sylte, and Sally E Johnson, and Lorraine M Sordillo
June 2005, Radiology,
Copied contents to your clipboard!