Conference Article| December 01 1990 Transport of polyamines in perfused porcine aortic endothelial cell microcarrier cultures RICHARD G. BOGLE; RICHARD G. BOGLE 1Section of Vascular Biology, M.R.C. Clinical Research Centre, Harrow, Middlesex, U.K. Search for other works by this author on: This Site PubMed Google Scholar DAVID M. L. MORGAN; DAVID M. L. MORGAN 1Section of Vascular Biology, M.R.C. Clinical Research Centre, Harrow, Middlesex, U.K. Search for other works by this author on: This Site PubMed Google Scholar JEREMY D. PEARSON; JEREMY D. PEARSON 1Section of Vascular Biology, M.R.C. Clinical Research Centre, Harrow, Middlesex, U.K. Search for other works by this author on: This Site PubMed Google Scholar GIOVANNI E. MANN GIOVANNI E. MANN * *To whom correspondence should be addressed at the following address: Biomedical Sciences Division, King's College London, Campden Hill Road, London W8 7AH, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1990) 18 (6): 1222–1223. https://doi.org/10.1042/bst0181222 Article history Received: June 18 1990 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation RICHARD G. BOGLE, DAVID M. L. MORGAN, JEREMY D. PEARSON, GIOVANNI E. MANN; Transport of polyamines in perfused porcine aortic endothelial cell microcarrier cultures. Biochem Soc Trans 1 December 1990; 18 (6): 1222–1223. doi: https://doi.org/10.1042/bst0181222 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1990 Biochemical Society1990 Article PDF first page preview Close Modal You do not currently have access to this content.

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10.1042/bst0181222

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Nrf2/ARE regulated antioxidant gene expression in endothelial and smooth muscle cells in oxidative stress: implications for atherosclerosis and preeclampsia.

PubMed (2007)

Giovanni E. Mann Jörg Niehueser-Saran Alan R. Watson Ling Gao Tetsuro Ishii

Increased generation of reactive oxygen species (ROS) in vascular diseases such as atherosclerosis, diabetes, chronic renal failure and preeclampsia readily leads to impaired endothelium-dependent relaxation and vascular injury. To counteract ROS- and electrophile-mediated injury, cells can induce a number of genes encoding phase II detoxifying enzymes and antioxidant proteins. A cis-acting transcriptional regulatory element, designated as antioxidant response element (ARE) or electrophile response element (EpRE), mediates the transcriptional activation of genes such as heme oxygenase-1, gamma-glutamylcysteine synthethase, thioredoxin reductase, glutathione-S-transferase and NAD(P)H:quinone oxidoreductase. Other antioxidant enzymes such as superoxide dismutase and catalase and non-enzymatic scavengers such as glutathione are also involved in scavenging ROS. Nuclear factor-erythroid 2-related factor 2 (Nrf2), a member of the Cap nno Collar family of basic region-leucine zipper (bZIP) transcription factors, plays an important role in ARE-mediated antioxidant gene expression. Kelch-like ECH-associated protein-1 (Keap1) normally sequesters Nrf2 in the cytoplasm in association with the actin cytoskeleton, but upon oxidation of cysteine residues Nrf2 dissociates from Keap1, translocates to the nucleus and binds to ARE sequences leading to transcriptional activation of antioxidant and phase II detoxifying genes. Protein kinase C (PKC), mitogen-activated protein kinases (MAPKs) and phosphotidylinositol 3-kinase (PI3K) have been implicated in the regulation of Nrf2/ARE signaling. We here review the evidence that the Nrf2/ARE signaling pathway plays an important role in vascular homeostasis and the defense of endothelial and smooth muscle cells against sustained oxidative stress associated with diseases such as atherosclerosis and preeclampsia.

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Impaired Redox Signaling and Antioxidant Gene Expression in Endothelial Cells in Diabetes: A Role for Mitochondria and the Nuclear Factor-E2-Related Factor 2-Kelch-Like ECH-Associated Protein 1 Defense Pathway

Antioxidants and Redox Signaling (2010)

Xinghua Cheng Richard Siow Giovanni E. Mann

Type 2 diabetes is an age-related disease associated with vascular pathologies, including severe blindness, renal failure, atherosclerosis, and stroke. Reactive oxygen species (ROS), especially mitochondrial ROS, play a key role in regulating the cellular redox status, and an overproduction of ROS may in part underlie the pathogenesis of diabetes and other age-related diseases. Cells have evolved endogenous defense mechanisms against sustained oxidative stress such as the redox-sensitive transcription factor nuclear factor E2-related factor 2 (Nrf2), which regulates antioxidant response element (ARE/electrophile response element)-mediated expression of detoxifying and antioxidant enzymes and the cystine/glutamate transporter involved in glutathione biosynthesis. We hypothesize that diminished Nrf2/ARE activity contributes to increased oxidative stress and mitochondrial dysfunction in the vasculature leading to endothelial dysfunction, insulin resistance, and abnormal angiogenesis observed in diabetes. Sustained hyperglycemia further exacerbates redox dysregulation, thereby providing a positive feedback loop for severe diabetic complications. This review focuses on the role that Nrf2/ARE-linked gene expression plays in regulating endothelial redox homeostasis in health and type 2 diabetes, highlighting recent evidence that Nrf2 may provide a therapeutic target for countering oxidative stress associated with vascular disease and aging. Antioxid. Redox Signal. 14, 469–488.

Mitochondrial ROS

Endothelial Dysfunction

10.1089/ars.2010.3283

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Modulation of the Cationic Amino Acid Transport System y+L by Surface Potential, Ouabain and Thrombin in Human Platelets: Effects of Uremia

Nephron Experimental Nephrology (2007)

Mariana Alves de Sá Siqueira Marcela Anjos Martins Natália Rodrigues Pereira Monique Bandeira Moss Sergio F. F. Santos

Background: Nitric oxide (NO), a key endogenous mediator involved in the maintenance of platelet function, is synthesized from the amino acid L-arginine. We have shown that L-arginine transport in platelets is rate-limiting for NO synthesis. A disturbance in the L-arginine-NO pathway in platelets was previously described in chronic renal failure (CRF) patients. Methods: Detailed kinetic studies were performed in platelets from controls (n = 60) and hemodialysis patients (n = 26). Results: The transport of L-arginine in platelets is mediated via system y+L, which is competitively inhibited by L-leucine in the presence of Na+ and by the irreversible inhibitor pCMB. In platelets, system y+L is markedly stimulated by an Na+/K+-ATPase inhibitor, ouabain, and by changes in surface potential, while it is downregulated by intraplatelet amino acid depletion (zero-trans) and by thrombin. In CRF patients, activation of L-arginine transport was limited to well-nourished patients compared to malnourished patients and controls, where it was reduced and did not differ significantly among the groups under zero-trans conditions. Conclusion: Our results provide the first evidence that system y+L in platelets is modulated by zero-trans conditions, surface potential, thrombin and intraplatelet Na+ concentration. Our findings suggest that enhanced transport in CRF involves increased L-arginine exchange with intraplatelet neutral amino acids.

10.1159/000111040

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Citations (8)