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Homocysteine attenuates endothelial haem oxygenase‐1 induction by nitric oxide (NO) and hypoxia
Author(s) -
Sawle Philip,
Foresti Roberta,
Green Colin J,
Motterlini Roberto
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)03117-9
Subject(s) - sodium nitroprusside , heme oxygenase , nitric oxide , hyperhomocysteinemia , hypoxia (environmental) , homocysteine , chemistry , oxygenase , biochemistry , cystathionine beta synthase , heme , medicine , endocrinology , biology , cysteine , enzyme , oxygen , organic chemistry
The disrupted metabolism of homocysteine (Hcy) causes hyperhomocysteinemia, a condition associated with the impairment of nitric oxide (NO) bio‐availability, tissue hypoxia and increased risk of vascular disease. Here, we examined how Hcy modulates the induction of the stress protein haem oxygenase‐1 (HO‐1) evoked by NO releasing agents and hypoxia in vascular endothelial cells. We found that Hcy (0.5 mM) markedly reduced the increase in haem oxygenase activity and HO‐1 protein expression induced by sodium nitroprusside (SNP, 0.5 mM) but did not affect HO‐1 activation mediated by S ‐nitroso‐ N ‐acetyl‐penicillamine. Cells pre‐treated with Hcy followed by addition of fresh medium containing SNP still exhibited an augmented haem oxygenase activity. Interestingly, high levels of Hcy were also able to abolish hypoxia‐mediated HO‐1 expression in a concentration‐dependent manner. These novel findings indicate that hyperhomocysteinemia interferes with crucial signaling pathways required by cells to respond and adapt to stressful conditions.