Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

TIMAP promotes angiogenesis by suppressing PTEN-mediated Akt inhibition in human glomerular endothelial cells

TIMAP promotes angiogenesis by suppressing PTEN-mediated Akt inhibition in human glomerular... Abstract The function of TIMAP, an endothelial cell (EC)-predominant protein phosphatase 1-regulatory subunit, is poorly understood. We explored the potential role of TIMAP in the Akt-dependent regulation of glomerular EC proliferation, survival, and in vitro angiogenesis. To deplete TIMAP, the EC were transfected with TIMAP-specific or nonspecific small interfering (si) RNA. The rate of electrical impedance development across subconfluent EC monolayers, a measure of the time-dependent increase in EC number, was 93 ± 2% lower in TIMAP-depleted than in control EC. This effect on cell proliferation was associated with reduced DNA synthesis and increased apoptosis: TIMAP silencing reduced 5-ethynyl-2′-deoxyuridine incorporation by 38 ± 2% during the exponential phase of EC proliferation, and cleaved caspase 3 as well as caspase 3 activity increased in TIMAP-depleted relative to control cells. Furthermore, TIMAP depletion inhibited the formation of angiogenic sprouts by glomerular EC in three-dimensional culture. TIMAP depletion strongly diminished growth factor-stimulated Akt phosphorylation without altering ERK1/2 phosphorylation, suggesting a specific effect on the PI3K/Akt/PTEN pathway. Endogenous TIMAP and PTEN colocalized in EC and coimmunoprecipitated from EC lysates. The inhibitory PTEN phosphorylation on S370 was significantly reduced in TIMAP-depleted compared with control EC, while phosphorylation of PTEN on the S380/T382/T383 cluster remained unchanged. Finally, the PTEN inhibitor bpV(phen) fully reversed the suppressive effect of TIMAP depletion on Akt phosphorylation. The data indicate that in growing EC, TIMAP is necessary for Akt-dependent EC proliferation, survival, and angiogenic sprout formation and that this effect of TIMAP is mediated by inhibition of the tumor suppressor PTEN. endothelial cells PTEN protein phosphatase 1-regulatory subunit PPP1R16B apoptosis clectric cell-substrate impedance sensing Copyright © 2014 the American Physiological Society View Full Text Previous Next Back to top Table of Contents Back Matter (PDF) Ed Board (PDF) Keywords endothelial cells PTEN protein phosphatase 1-regulatory subunit PPP1R16B apoptosis clectric cell-substrate impedance sensing Article Abstract MATERIALS AND METHODS RESULTS DISCUSSION GRANTS DISCLOSURES AUTHOR CONTRIBUTIONS ACKNOWLEDGMENTS REFERENCES Figures & Data Info PDF Alert me when this article is cited Alert me if a correction is posted Email Thank you for your interest in spreading the word on Renal Physiology. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following TIMAP promotes angiogenesis by suppressing PTEN-mediated Akt inhibition in human glomerular endothelial cells Message Subject (Your Name) has sent you a message from Renal Physiology Message Body (Your Name) thought you would like to see the Renal Physiology web site. Your Personal Message Print Citation Tools TIMAP promotes angiogenesis by suppressing PTEN-mediated Akt inhibition in human glomerular endothelial cells Marya Obeidat , Laiji Li , Barbara J. Ballermann American Journal of Physiology - Renal Physiology Sep 2014, 307 (5) F623-F633; DOI: 10.1152/ajprenal.00070.2014 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Request Permissions Share TIMAP promotes angiogenesis by suppressing PTEN-mediated Akt inhibition in human glomerular endothelial cells Marya Obeidat , Laiji Li , Barbara J. Ballermann American Journal of Physiology - Renal Physiology Sep 2014, 307 (5) F623-F633; DOI: 10.1152/ajprenal.00070.2014 Permalink: Copy View Full Page PDF Tweet Widget Facebook Like Google Plus One Reddit CiteULike Mendeley StumbleUpon More in this TOC Section Intrauterine growth restriction programs an accelerated age-related increase in cardiovascular risk in male offspring The role of Nedd4-1 WW domains in binding and regulating human organic anion transporter 1 The NHERF1 PDZ1 domain and IRBIT interact and mediate the activation of Na + /H + exchanger 3 by ANG II Show more Articles Related Articles No related articles found. Web of Science Scopus PubMed Google Scholar Cited By... No citing articles found. Web of Science (1) Scopus (2) Google Scholar Calls for Papers Most Cited Most Read Imaging techniques in renal (patho)physiology research - Submission Deadline June 30, 201 7 Inflammation and Inflammatory Mediators in Kidney Disease - Submission Deadline June 30, 201 7 Mechanism and treatment of renal fibrosis - Submission Deadline June 30, 201 7 Renal Hemodynamics - Submission Deadline: June 30, 2017 Gender and Hormones in Lower Urinary Tract Function - Submission Deadline: June 30, 2017 Featured Articles Featured Podcasts Mild systemic thermal therapy ameliorates renal dysfunction in a rodent model of chronic kidney disease Resistant starch alters gut microbiome and metabolomic profiles concurrent with amelioration of chronic kidney disease in rats Evidence for a mitochondrial angiotensin-(1–7) system in the kidney Glt1 glutamate receptor mediates the establishment and perpetuation of chronic visceral pain in an animal model of stress-induced bladder hyperalgesia A mild reduction of food intake slows disease progression in an orthologous mouse model of polycystic kidney disease GA_googleFillSlot("ajprenal_tower_right_160x600"); Navigate Current Issue Articles in Press Archives Feedback Submit Subscribe Personal Alerts More Information About this Journal Information for Authors Submit a Manuscript Press Advertising AuthorChoice Calls for Papers Ethics Policies PubMed Central Policy Reprints and Permissions Institutional Administrators APS Publications News Follow APS Publications on Twitter American Physiological Society Journals Cell Physiology Advances in Physiology Education Comprehensive Physiology Endocrinology and Metabolism Gastrointestinal and Liver Physiology Heart and Circulatory Physiology Journal of Applied Physiology Journal of Neurophysiology Lung Cellular and Molecular Physiology Physiological Genomics Physiological Review Physiology Regulatory, Integrative and Comparative Physiology Renal Physiology Physiological Reports Legacy Content APS Select www.physiology.org American Journal of Physiology - Renal Physiology® and the APS® logo are registered trademarks of the American Physiological Society | Print ISSN: 1931-857X | Online ISSN: 1522-1466 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Renal Physiology The American Physiological Society

TIMAP promotes angiogenesis by suppressing PTEN-mediated Akt inhibition in human glomerular endothelial cells

Loading next page...
 
/lp/the-american-physiological-society/timap-promotes-angiogenesis-by-suppressing-pten-mediated-akt-46wsIOdwB6

References

References for this paper are not available at this time. We will be adding them shortly, thank you for your patience.

Publisher
The American Physiological Society
Copyright
Copyright © 2014 the American Physiological Society
ISSN
0363-6127
eISSN
1522-1466
DOI
10.1152/ajprenal.00070.2014
pmid
25007873
Publisher site
See Article on Publisher Site

Abstract

Abstract The function of TIMAP, an endothelial cell (EC)-predominant protein phosphatase 1-regulatory subunit, is poorly understood. We explored the potential role of TIMAP in the Akt-dependent regulation of glomerular EC proliferation, survival, and in vitro angiogenesis. To deplete TIMAP, the EC were transfected with TIMAP-specific or nonspecific small interfering (si) RNA. The rate of electrical impedance development across subconfluent EC monolayers, a measure of the time-dependent increase in EC number, was 93 ± 2% lower in TIMAP-depleted than in control EC. This effect on cell proliferation was associated with reduced DNA synthesis and increased apoptosis: TIMAP silencing reduced 5-ethynyl-2′-deoxyuridine incorporation by 38 ± 2% during the exponential phase of EC proliferation, and cleaved caspase 3 as well as caspase 3 activity increased in TIMAP-depleted relative to control cells. Furthermore, TIMAP depletion inhibited the formation of angiogenic sprouts by glomerular EC in three-dimensional culture. TIMAP depletion strongly diminished growth factor-stimulated Akt phosphorylation without altering ERK1/2 phosphorylation, suggesting a specific effect on the PI3K/Akt/PTEN pathway. Endogenous TIMAP and PTEN colocalized in EC and coimmunoprecipitated from EC lysates. The inhibitory PTEN phosphorylation on S370 was significantly reduced in TIMAP-depleted compared with control EC, while phosphorylation of PTEN on the S380/T382/T383 cluster remained unchanged. Finally, the PTEN inhibitor bpV(phen) fully reversed the suppressive effect of TIMAP depletion on Akt phosphorylation. The data indicate that in growing EC, TIMAP is necessary for Akt-dependent EC proliferation, survival, and angiogenic sprout formation and that this effect of TIMAP is mediated by inhibition of the tumor suppressor PTEN. endothelial cells PTEN protein phosphatase 1-regulatory subunit PPP1R16B apoptosis clectric cell-substrate impedance sensing Copyright © 2014 the American Physiological Society View Full Text Previous Next Back to top Table of Contents Back Matter (PDF) Ed Board (PDF) Keywords endothelial cells PTEN protein phosphatase 1-regulatory subunit PPP1R16B apoptosis clectric cell-substrate impedance sensing Article Abstract MATERIALS AND METHODS RESULTS DISCUSSION GRANTS DISCLOSURES AUTHOR CONTRIBUTIONS ACKNOWLEDGMENTS REFERENCES Figures & Data Info PDF Alert me when this article is cited Alert me if a correction is posted Email Thank you for your interest in spreading the word on Renal Physiology. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following TIMAP promotes angiogenesis by suppressing PTEN-mediated Akt inhibition in human glomerular endothelial cells Message Subject (Your Name) has sent you a message from Renal Physiology Message Body (Your Name) thought you would like to see the Renal Physiology web site. Your Personal Message Print Citation Tools TIMAP promotes angiogenesis by suppressing PTEN-mediated Akt inhibition in human glomerular endothelial cells Marya Obeidat , Laiji Li , Barbara J. Ballermann American Journal of Physiology - Renal Physiology Sep 2014, 307 (5) F623-F633; DOI: 10.1152/ajprenal.00070.2014 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Request Permissions Share TIMAP promotes angiogenesis by suppressing PTEN-mediated Akt inhibition in human glomerular endothelial cells Marya Obeidat , Laiji Li , Barbara J. Ballermann American Journal of Physiology - Renal Physiology Sep 2014, 307 (5) F623-F633; DOI: 10.1152/ajprenal.00070.2014 Permalink: Copy View Full Page PDF Tweet Widget Facebook Like Google Plus One Reddit CiteULike Mendeley StumbleUpon More in this TOC Section Intrauterine growth restriction programs an accelerated age-related increase in cardiovascular risk in male offspring The role of Nedd4-1 WW domains in binding and regulating human organic anion transporter 1 The NHERF1 PDZ1 domain and IRBIT interact and mediate the activation of Na + /H + exchanger 3 by ANG II Show more Articles Related Articles No related articles found. Web of Science Scopus PubMed Google Scholar Cited By... No citing articles found. Web of Science (1) Scopus (2) Google Scholar Calls for Papers Most Cited Most Read Imaging techniques in renal (patho)physiology research - Submission Deadline June 30, 201 7 Inflammation and Inflammatory Mediators in Kidney Disease - Submission Deadline June 30, 201 7 Mechanism and treatment of renal fibrosis - Submission Deadline June 30, 201 7 Renal Hemodynamics - Submission Deadline: June 30, 2017 Gender and Hormones in Lower Urinary Tract Function - Submission Deadline: June 30, 2017 Featured Articles Featured Podcasts Mild systemic thermal therapy ameliorates renal dysfunction in a rodent model of chronic kidney disease Resistant starch alters gut microbiome and metabolomic profiles concurrent with amelioration of chronic kidney disease in rats Evidence for a mitochondrial angiotensin-(1–7) system in the kidney Glt1 glutamate receptor mediates the establishment and perpetuation of chronic visceral pain in an animal model of stress-induced bladder hyperalgesia A mild reduction of food intake slows disease progression in an orthologous mouse model of polycystic kidney disease GA_googleFillSlot("ajprenal_tower_right_160x600"); Navigate Current Issue Articles in Press Archives Feedback Submit Subscribe Personal Alerts More Information About this Journal Information for Authors Submit a Manuscript Press Advertising AuthorChoice Calls for Papers Ethics Policies PubMed Central Policy Reprints and Permissions Institutional Administrators APS Publications News Follow APS Publications on Twitter American Physiological Society Journals Cell Physiology Advances in Physiology Education Comprehensive Physiology Endocrinology and Metabolism Gastrointestinal and Liver Physiology Heart and Circulatory Physiology Journal of Applied Physiology Journal of Neurophysiology Lung Cellular and Molecular Physiology Physiological Genomics Physiological Review Physiology Regulatory, Integrative and Comparative Physiology Renal Physiology Physiological Reports Legacy Content APS Select www.physiology.org American Journal of Physiology - Renal Physiology® and the APS® logo are registered trademarks of the American Physiological Society | Print ISSN: 1931-857X | Online ISSN: 1522-1466

Journal

AJP - Renal PhysiologyThe American Physiological Society

Published: Sep 1, 2014

There are no references for this article.