Homocysteine-Induced Endoplasmic Reticulum Stress and Growth Arrest Leads to Specific Changes in Gene Expression in Human Vascular Endothelial Cells
10.1182/blood.v94.3.959.415k20_959_967
Crossref journal-article
American Society of Hematology
Blood (234)
Abstract

Alterations in the cellular redox potential by homocysteine promote endothelial cell (EC) dysfunction, an early event in the progression of atherothrombotic disease. In this study, we demonstrate that homocysteine causes endoplasmic reticulum (ER) stress and growth arrest in human umbilical vein endothelial cells (HUVEC). To determine if these effects reflect specific changes in gene expression, cDNA microarrays were screened using radiolabeled cDNA probes generated from mRNA derived from HUVEC, cultured in the absence or presence of homocysteine. Good correlation was observed between expression profiles determined by this method and by Northern blotting. Consistent with its adverse effects on the ER, homocysteine alters the expression of genes sensitive to ER stress (ie, GADD45, GADD153, ATF-4, YY1). Several other genes observed to be differentially expressed by homocysteine are known to mediate cell growth and differentiation (ie, GADD45, GADD153, Id-1, cyclin D1, FRA-2), a finding that supports the observation that homocysteine causes a dose-dependent decrease in DNA synthesis in HUVEC. Additional gene profiles also show that homocysteine decreases cellular antioxidant potential (glutathione peroxidase, NKEF-B PAG, superoxide dismutase, clusterin), which could potentially enhance the cytotoxic effects of agents or conditions known to cause oxidative damage. These results successfully demonstrate the use of cDNA microarrays in identifying homocysteine-respondent genes and indicate that homocysteine-induced ER stress and growth arrest reflect specific changes in gene expression in human vascular EC.

Bibliography

Outinen, P. A., Sood, S. K., Pfeifer, S. I., Pamidi, S., Podor, T. J., Li, J., Weitz, J. I., & Austin, R. C. (1999). Homocysteine-Induced Endoplasmic Reticulum Stress and Growth Arrest Leads to Specific Changes in Gene Expression in Human Vascular Endothelial Cells. Blood, 94(3), 959–967.

Authors 8
  1. P. Andrew Outinen (first)
  2. Sudesh K. Sood (additional)
  3. Sabine I. Pfeifer (additional)
  4. Sushmita Pamidi (additional)
  5. Thomas J. Podor (additional)
  6. Jun Li (additional)
  7. Jeffrey I. Weitz (additional)
  8. Richard C. Austin (additional)
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Dates
Type When
Created 5 years, 10 months ago (Oct. 11, 2019, 7:58 a.m.)
Deposited 4 years, 7 months ago (Jan. 24, 2021, 10:08 a.m.)
Indexed 1 week, 2 days ago (Aug. 21, 2025, 1:29 p.m.)
Issued 26 years ago (Aug. 1, 1999)
Published 26 years ago (Aug. 1, 1999)
Published Print 26 years ago (Aug. 1, 1999)
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