Formation of lipid raft redox signalling platforms in glomerular endothelial cells: an early event of homocysteine-induced glomerular injury.
Formation of lipid raft redox signalling platforms in glomerular endothelial cells: an early event of homocysteine-induced glomerular injury.
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DOI：
10.1111/j.1582-4934.2009.00743.x
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发表时间：
2009-09
影响因子：
5.3
通讯作者：
Li PL
中科院分区：
文献类型：
--
作者：
Yi F;Jin S;Zhang F;Xia M;Bao JX;Hu J;Poklis JL;Li PL
本研究验证了同型半胱氨酸(Hcys)诱导神经酰胺的产生刺激肾小球内皮细胞(GEC)膜上聚集的脂筏(LRs)通过聚集和激活NADPH氧化酶亚基形成氧化还原信号平台，从而增加超氧化物(O2.−)的产生，导致肾小球内皮功能障碍和最终损伤或硬化的假说。利用共聚焦显微镜，我们首次证明了在Hcys刺激下，LR簇与NADPH氧化酶亚单位gp91Phox和p47Phox共存于GECs膜中。免疫印迹分析发现，在LR组分中，NADPH氧化酶亚基gp91Phox和p47Phox得到了丰富，该酶的活性显著提高。我们还检测了升高的Hcys对GECs单层通透性的影响。结果发现，Hcys显著增加了GEC的通透性，这一作用可被抑制LR氧化还原信号平台的形成所阻断。最后，我们发现Hcys诱导的GEC通透性增强与通过这些LR-氧化还原平台调节微管稳定性有关。结论：Hcys对肾小球内皮细胞的早期损伤作用与通过LR聚集形成氧化还原信号平台有关，这可能通过破坏肾小管上皮细胞的微管网络而导致肾小球通透性增加。
The present study tested the hypothesis that homocysteine (Hcys)-induced ceramide production stimulates lipid rafts (LRs) clustering on the membrane of glomerular endothelial cells (GECs) to form redox signalling platforms by aggregation and activation of NADPH oxidase subunits and thereby enhances superoxide (O2.−) production, leading to glomerular endothelial dysfunction and ultimate injury or sclerosis. Using confocal microscopy, we first demonstrated a co-localization of LR clusters with NADPH oxidase subunits, gp91phox and p47phox in the GECs membrane upon Hcys stimulation. Immunoblot analysis of floated detergent-resistant membrane fractions found that in LR fractions NADPH oxidase subunits gp91phox and p47phox are enriched and that the activity of this enzyme dramatically increased. We also examined the effect of elevated Hcys on the cell monolayer permeability in GECs. It was found that Hcys significantly increased GEC permeability, which was blocked by inhibition of LR redox signalling platform formation. Finally, we found that Hcys-induced enhancement of GEC permeability is associated with the regulation of microtubule stability through these LR-redox platforms. It is concluded that the early injurious effect of Hcys on the glomerular endothelium is associated with the formation of redox signalling platforms via LR clustering, which may lead to increases in glomerular permeability by disruption of microtubule network in GECs.
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影响因子：
19.6
作者：
ADLER, S;ENG, B
通讯作者：
ENG, B
影响因子：
4.8
作者：
Bernhard, D;Csordas, A;Wick, G
通讯作者：
Wick, G
影响因子：
4.1
作者：
Fillet, M;Van Heugen, JC;Crommen, J
通讯作者：
Crommen, J
DOI：
10.1161/atvbaha.107.159772
发表时间：
2008-03-01
影响因子：
8.7
作者：
Jin, Si;Zhang, Yang;Li, Pin-Lan
通讯作者：
Li, Pin-Lan
影响因子：
4.2
作者：
Mills, JL;Scott, JM;Lee, YJ
通讯作者：
Lee, YJ