FOXO1 mediates the autocrine effect of endothelin-1 on endothelial cell survival.

Molecular Endocrinology
Vincenza CifarelliH Henry Dong

Abstract

Chronic hyperglycemia exerts a deleterious effect on endothelium, contributing to endothelial dysfunction and microvascular complications in poorly controlled diabetes. To understand the underlying mechanism, we studied the effect of endothelin-1 (ET-1) on endothelial production of Forkhead box O1 (FOXO1), a forkhead transcription factor that plays an important role in cell survival. ET-1 is a 21-amino acid peptide that is secreted primarily from endothelium. Using adenovirus-mediated gene transfer approach, we delivered FOXO1 cDNA into cultured human aorta endothelial cells. FOXO1 was shown to stimulate B cell leukemia/lymphoma 2-associated death promoter (BAD) production and promote cellular apoptosis. This effect was counteracted by ET-1. In response to ET-1, FOXO1 was phosphorylated and translocated from the nucleus to cytoplasm, resulting in inhibition of BAD production and mitigation of FOXO1-mediated apoptosis. Hyperglycemia stimulated FOXO1 O-glycosylation and promoted its nuclear localization in human aorta endothelial cells. This effect accounted for unbridled FOXO1 activity in the nucleus, contributing to augmented BAD production and endothelial apoptosis under hyperglycemic conditions. FOXO1 expression became deregu...Continue Reading

References

Oct 1, 1992·Diabetes Care·M KawamuraY Omori
May 1, 1990·Diabetologia·K TakahashiS R Bloom
Oct 22, 1993·Cell·D M HockenberyS J Korsmeyer
May 1, 1997·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·C LetiziaA Iannacone
Jun 23, 1999·Proceedings of the National Academy of Sciences of the United States of America·W H BiggsK C Arden
Apr 12, 2003·Science·Siu Sylvia LeeGary Ruvkun
Jul 29, 2003·Diabetes·Jason J WilkesJerrold Olefsky
Sep 19, 2003·Proceedings of the National Academy of Sciences of the United States of America·Hitomi MatsuzakiAkiyoshi Fukamizu
Mar 10, 2004·The Biochemical Journal·Lars P Van Der HeideMarten P Smidt
Sep 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Masahiro AokiPeter K Vogt
Nov 17, 2004·The Journal of Clinical Investigation·Jennifer AltomonteHengjiang Henry Dong
Jan 26, 2005·Proceedings of the National Academy of Sciences of the United States of America·Haojie HuangDonald J Tindall
Apr 30, 2005·Trends in Endocrinology and Metabolism : TEM·Andreas BarthelTerry G Unterman
Jul 20, 2005·Neoplasia : an International Journal for Oncology Research·Joel B NelsonBeth R Pflug
Apr 26, 2006·Circulation·Brian DeBoschAnthony J Muslin
Sep 21, 2006·American Journal of Physiology. Endocrinology and Metabolism·Ching Fai KwokLow-Tone Ho
Jan 18, 2007·American Journal of Physiology. Endocrinology and Metabolism·Maria A PotenzaMonica Montagnani
Apr 25, 2007·Apoptosis : an International Journal on Programmed Cell Death·Lisenn LalierFrançois M Vallette
May 31, 2007·Journal of the American College of Nutrition·Michael E WidlanskyJoseph A Vita
Apr 19, 2008·The Journal of Biological Chemistry·Michael P HousleyGerald W Hart
May 24, 2008·The Journal of Clinical Investigation·Adama KamagateH Henry Dong

❮ Previous
Next ❯

Citations

Mar 19, 2014·Cellular and Molecular Life Sciences : CMLS·Ping Song, Ming-Hui Zou
Mar 10, 2016·Cardiovascular Diabetology·Vidya KandulaMichael G Irwin
Jan 18, 2013·Journal of Diabetes·Dae Hyun KimH Henry Dong
May 7, 2015·Biochemical and Biophysical Research Communications·Yann FardiniTarik Issad
Nov 1, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yann FardiniTarik Issad
Apr 1, 2014·Endocrine Journal·Zilong Cao, Xiaoyu Wang
Feb 19, 2017·The Journal of Endocrinology·Sojin Lee, H Henry Dong
Mar 28, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michele BiagioliStefano Fiorucci
Jun 25, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sun-Jin KimIsaiah J Fidler
May 13, 2021·Drug Design, Development and Therapy·Xiaojun ZhangHuimin Liu

❮ Previous
Next ❯

Related Concepts

Related Feeds

B-Cell Leukemia (Keystone)

B-cell leukemia includes various types of lymphoid leukemia that affect B cells. Here is the latest research on B-cell leukemia.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis