ABCA1 p.Ser63Ala
| Predicted by SNAP2: | A: D (59%), C: D (80%), D: D (91%), E: D (91%), F: D (91%), G: D (85%), H: D (85%), I: D (91%), K: D (91%), L: D (91%), M: D (85%), N: D (85%), P: D (91%), Q: D (85%), R: D (91%), T: D (80%), V: D (80%), W: D (91%), Y: D (91%), |
| Predicted by PROVEAN: | A: N, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, T: D, V: D, W: D, Y: D, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] Activating transcription factor 1 directs Mhem ath... Circ Res. 2012 Jan 6;110(1):20-33. Epub 2011 Nov 3. Boyle JJ, Johns M, Kampfer T, Nguyen AT, Game L, Schaer DJ, Mason JC, Haskard DO
Activating transcription factor 1 directs Mhem atheroprotective macrophages through coordinated iron handling and foam cell protection.
Circ Res. 2012 Jan 6;110(1):20-33. Epub 2011 Nov 3., [PMID:22052915]
Abstract [show]
RATIONALE: Intraplaque hemorrhage (IPH) drives atherosclerosis through the dual metabolic stresses of cholesterol-enriched erythrocyte membranes and pro-oxidant heme/iron. When clearing tissue hemorrhage, macrophages are typically seen storing either iron or lipid. We have recently defined hemorrhage-associated macrophages (HA-mac) as a plaque macrophage population that responds adaptively to IPH. OBJECTIVE: This study aimed to define the key transcription factor(s) involved in HO-1 induction by heme. METHODS AND RESULTS: To address this question, we used microarray analysis and transfection with siRNA and plasmids. To maintain physiological relevance, we focused on human blood-derived monocytes. We found that heme stimulates monocytes through induction of activating transcription factor 1 (ATF-1). ATF-1 coinduces heme oxygenase-1 (HO-1) and Liver X receptor beta (LXR-beta). Heme-induced HO-1 and LXR-beta were suppressed by knockdown of ATF-1, and HO-1 and LXR-beta were induced by ATF-1 transfection. ATF-1 required phosphorylation for full functional activity. Expression of LXR-beta in turn led to induction of other genes central to cholesterol efflux, such as LXR-alpha and ABCA1. This heme-directed state was distinct from known macrophage states (M1, M2, Mox) and, following the same format, we have designated them Mhem. CONCLUSIONS: These results show that ATF-1 mediates HO-1 induction by heme and drives macrophage adaptation to intraplaque hemorrhage. Our definition of an ATF-1-mediated pathway for linked protection from foam cell formation and oxidant stress may have therapeutic potential.
Comments [show]
None has been submitted yet.
No. Sentence Comment
82 Finally, transfection of ATF-1, but not unrelated plasmids or a Ser63-Ala nonphosphorylatable mu- Figure 2.
X
ABCA1 p.Ser63Ala 22052915:82:64
status: NEW81 Finally, transfection of ATF-1, but not unrelated plasmids or a Ser63-Ala nonphosphorylatable mu- Figure 2.
X
ABCA1 p.Ser63Ala 22052915:81:64
status: NEW