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Ets‐1 and the mitogen activated protein kinases are modulated by nitric oxide
Author(s) -
Kelland Cassandra,
Milkiewicz Malgorzata,
Haas Tara L
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.a712
Subject(s) - p38 mitogen activated protein kinases , snap , kinase , phosphorylation , chemistry , nitric oxide , mapk/erk pathway , protein kinase a , mitogen activated protein kinase , microbiology and biotechnology , biophysics , biochemistry , biology , computer graphics (images) , organic chemistry , computer science
Luminal splitting via internal division of capillaries is a form of angiogenesis caused by increased shear stress. While the mechanism behind luminal splitting is unknown, it is known that nitric oxide (NO) production and the mitogen activated protein (MAP) kinases are affected by shear stress. The transcription factor Ets‐1 is known to cause transcription of many proteins used in angiogenesis. We hypothesized that shear stress increases Ets‐1 via NO and the MAP kinases. Skeletal muscle endothelial cells (SMEC) were exposed to shear stress with or without the NO inhibitor L‐NG‐Nitroarginine (LNNA), and Ets‐1 mRNA was measured. Ets‐1 mRNA increased 4‐fold (± 1.4) after 2 hours of shear stress compared to control (p=0.003, n=3), and this was attenuated by LNNA (1.8 ± 0.4 fold increase vs. control, ns, n=3). SMEC stimulated by the NO donor S‐nitroso‐N‐acetylpenicillamine (SNAP) for 2 hours showed a trend towards an increase in Ets‐1 protein at 10 μM SNAP (1.5 ± 0.2 fold increase, p=0.06, n=3), but no change in Ets‐1 protein at 100 μM SNAP (1.0 ± 0.3, ns, n=3). Stimulation of SMEC with 100 μM SNAP caused a trend towards an increase in p38 phosphorylation (2.16 ± 0.5, p=0.08, n=3), a decrease in ERK phosphorylation (0.5 ± 0.14, p=0.02, n=3), and no change in phosphorylated c‐jun (1.3 ± 0.24, ns, n=2). These experiments will be repeated using 10 μM SNAP to determine if a dose‐dependent effect is occurring. Our results support a role for shear stress modulation of Ets‐1 via NO. Further studies will clarify the involvement of the MAP kinases in this signal pathway. Funded by CIHR.