Journal
APOPTOSIS
Volume 12, Issue 11, Pages 1979-1988Publisher
SPRINGER
DOI: 10.1007/s10495-007-0123-3
Keywords
arachidonic acid; EET; cell proliferation; cell death; cytochrome P-450; eicosanoids
Categories
Ask authors/readers for more resources
Previous studies have demonstrated that arachidonic acid (AA) metabolites released by the cyclooxygenase pathway is involved in serum-induced 3T6 fibroblast cycle progression and proliferation. However, these results also suggest that other AA cascade pathways might be involved. Recently, we also described the role of hydroxyeicosatetraenoic acids, which are produced by cytochrome P450 monooxygenases (CYP), in 3T6 fibroblast growth. AA can be also metabolized by the epoxygenase activity of CYP-producing epoxyeicosatrienoic acids (EETs). Finally, the cytosolic epoxide hydrolases catalyze the hydration of the EETs, transforming them into dihydroxyeicosatetraenoic acids (DHETEs). In this work, we have studied the role of the EETs/DHETEs on 3T6 fibroblasts growth. Our results show that PDGF stimulates 3T6 fibroblast proliferation and [H-3]thymidine incorporation, while the addition of 5,6-EET, 8,9-EET, 11,12-EET or 14,15-EET (0.1-1 mu M) inhibit these processes. Furthermore, 5,6-DHETE and 11,12-DHETE (0.1-1 mu M) also inhibit cell proliferation and DNA synthesis. Interestingly, this growth inhibition was correlated with an induction of apoptosis. Thus, we observed that in the presence of PDGF, EETs or DHETEs (0.1-1 mu M) induce phosphatidylserine externalization (as measured by annexin V-binding) and DNA fragmentation (as quantified using a TUNEL assay). Our results show that calpain, as well as caspase-12 and caspase-3, are involved in these events. Therefore, EETs and DHETEs have anti-proliferative and pro-apoptotic effects on PDGF-stimulated 3T6 fibroblasts.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available