Palmitate alters neuregulin signaling and biology in cardiac myocytes.
Palmitate alters neuregulin signaling and biology in cardiac myocytes.
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DOI：
10.1016/j.bbrc.2008.11.150
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发表时间：
2009-01-30
影响因子：
3.1
通讯作者：
Sawyer, Douglas B.
中科院分区：
文献类型：
--
作者：
Miller, Thomas A.;Icli, Basak;Cote, Gregory M.;LeBrasseur, Nathan K.;Borkan, Steve C.;Pimentel, David R.;Peng, Xuyang;Sawyer, Douglas B.
饱和脂肪酸棕榈酸酯通过破坏细胞信号来改变正常细胞功能，这些影响与血脂异常相关的终末器官损伤有关。神经调节蛋白-1β (NRG-1β)是心肌细胞的生长和存活因子。我们验证了棕榈酸盐改变离体新生大鼠心肌细胞NRG-1β信号和生物学的假设。棕榈酸酯处理抑制肌细胞中PI3kinase/Akt通路的NRG-1β活化。我们发现，NRG-1β处理可提高棕榈酸酯的促凋亡活性。棕榈酸酯对NRG-1β信号传导和存活的影响被单不饱和脂肪酸油酸酯逆转。在控制条件下，NRG-1β降低肌细胞中p53的表达。在棕榈酸盐存在的情况下，NRG-1β引起p53表达增加，bax多聚体形成，同时mdm2 （p53的负调节因子）降解。因此，当棕榈酸盐存在时，NRG-1β激活心肌细胞的促凋亡信号，而不是促存活信号。
The saturated fatty acid palmitate alters normal cell function via disruption of cell signaling, and these effects have been implicated in the end-organ damage associated with dyslipidemia. Neuregulin-1β (NRG-1β) is a growth and survival factor in cardiac myocytes. We tested the hypothesis that palmitate alters NRG-1β signaling and biology in isolated neonatal rat cardiac myocytes. Palmitate treatment inhibited NRG-1β activation of the PI3kinase/Akt pathway in myocytes. We found that the pro-apoptotic activity of palmitate was increased by NRG-1β treatment. The effects of palmitate on NRG-1β signaling and survival were reversed by the mono-unsaturated fatty acid oleate. Under control conditions NRG-1β decreases p53 expression in myocytes. In the presence of palmitate, NRG-1β caused an increase in p53 expression, bax multimer formation, concurrent with degradation of mdm2, a negative regulator of p53. Thus in the presence of palmitate NRG-1β activates pro-apoptotic, rather than pro-survival signaling in cardiac myocytes.
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影响因子：
4.8
作者：
Listenberger, LL;Ory, DS;Schaffer, JE
通讯作者：
Schaffer, JE
影响因子：
5
作者：
Fukazawa, R;Miller, TA;Sawyer, DB
通讯作者：
Sawyer, DB
DOI：
10.1152/ajpheart.1999.277.5.h2026
发表时间：
1999-11-01
影响因子：
4.8
作者：
Baliga, RR;Pimental, DR;Kelly, RA
通讯作者：
Kelly, RA
影响因子：
64.8
作者：
GASSMANN, M;CASAGRANDA, F;LEMKE, G
通讯作者：
LEMKE, G
DOI：
10.1016/j.bbrc.2005.08.088
发表时间：
2005-10-14
影响因子：
3.1
作者：
Miller, TA;LeBrasseur, NK;Sawyer, DB
通讯作者：
Sawyer, DB