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Homocysteine (HCys) induces apoptosis in rat aorta endothelial cells (RAEC): Role of NMDA receptor and MAP kinase (MAPK)
Author(s) -
Brown Aliza,
Chen Hongjiang,
Monaghan Daniel T.,
Moursi Mohammed M.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a198
Subject(s) - mapk/erk pathway , apoptosis , p38 mitogen activated protein kinases , microbiology and biotechnology , kinase , chemistry , medicine , biology , biochemistry
HCys is associated with both cell proliferation and apoptosis. Previously, HCys increased intimal proliferation in the endarterectomized rat carotid artery; induced cell growth in both vascular smooth muscle cells and RAECs, which was associated with the upregulation of NMDAr expression. This study observed the effect of HCys on apoptosis of RAECs and its possible mechanism. RAECs 5–7 th passage were used to observe the effect of HCys on apoptosis and MAPK expression and activation. RAECs were respectively treated with HCys concentrations of 0, 2, 10, 50, 250 μM and 1, 5 mM or with 50 μM HCys at 0, 15 and 30 mins and 1, 3, 6, 12, 24 hrs. To examine the role of NMDAr in apoptosis, prior to treatment with HCys, RAECs were preincubated with MK‐801 (NMDAr antagonist) or PPDA (NMDAr 2D subunit antagonist). To explore activation pathways, RAECs were preincubated with PD95059 (ERK‐MAPK antagonist) or SB202190 (p38‐MAPK antagonist). PARP expression by Western blot and DNA laddering were applied to detected apoptosis, Western blot was used to determine the expression/activation of MAPK. HCys induced apoptosis in RAECs in dose‐ and time‐manner indicated by increased degradation of PARP. Interestingly, 5 mM HCys decreased apoptosis, HCys also upregulated activated p38 MAPK but not total p38 MAPK or total/activated ERK MAPK. MK‐801, but not PPDA attenuated the HCys‐induced apoptosis and activation of p38 MAPK. Moreover, SB202190, but not PD98059 decreased HCys‐induced apoptosis. The results indicate that HCys induced apoptosis may be mediated by the NMDAr and p38, but not ERK MAPK pathways.