Advanced glycation end products inhibit Na+ K+ ATPase in proximal tubule epithelial cells: role of cytosolic phospholipase A2alpha and phosphatidylinositol 4-phosphate 5-kinase gamma.
Advanced glycation end products inhibit Na+ K+ ATPase in proximal tubule epithelial cells: role of cytosolic phospholipase A2alpha and phosphatidylinositol 4-phosphate 5-kinase gamma.
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晚期糖基化终产物抑制近曲小管上皮细胞中的 Na K ATP 酶：胞浆磷脂酶 A2α 和磷脂酰肌醇 4-磷酸 5-激酶 γ 的作用。
DOI：
10.1016/j.bbamcr.2010.04.009
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
L. Bach
中科院分区：
文献类型：
--
作者：
M. Gallicchio;L. Bach
糖尿病期间的慢性高血糖导致蛋白质的非酶糖基化，形成晚期糖基化终产物（AGEs），从而导致肾病。在糖尿病中，肾Na+K+ atp酶（NKA）活性下调，磷酸肌肽代谢上调。我们检测了AGEs对猪LLC-PK1和人HK2近端小管上皮细胞NKA活性的影响。通过免疫荧光显微镜和薄层色谱检测，AGE-BSA增加了细胞磷酸肌醇4,5二磷酸（PIP2）的产生。AGE-BSA （40μM）通过激活胞质磷脂酶A2（cPLA2）诱导3h -花生四烯酸释放和活性氧（ROS）产生。免疫荧光染色和[86Rb+]摄取测定显示，在几分钟内，AGE-BSA显著抑制NKA表面表达和活性，呈剂量依赖性和时间依赖性，表明AGEs通过刺激NKA的内吞作用来抑制NKA。age - bsa诱导的细胞表面NKA下降被cPLA2α抑制剂、PIP2抑制剂新霉素和Src抑制剂PP2逆转。AGE-BSA增加了NKA与AP-2网格蛋白核接头复合物α-适应素的结合，但对β2或μ2适应素亚基没有作用。用PIP5Kγ siRNA转染HK2细胞可阻止AGE-BSA抑制NKA活性。AGEs可能刺激PIP5Kγ增加PIP2的产生，这可能增强AP-2对网格蛋白坑的定位，增加网格蛋白坑的形成，增强AP-2对NKA货物的识别和/或刺激cPLA2α的活性。这些结果表明，AGEs通过网格蛋白介导的内吞作用调节花生四烯酸和磷酸肌肽代谢，从而抑制NKA。阐明新的细胞内AGE信号通路可能会改善糖尿病肾病的治疗方法。
Chronic hyperglycaemia during diabetes leads to non-enzymatic glycation of proteins to form advanced glycation end products (AGEs) that contribute to nephropathy. In diabetes, renal Na+K+ATPase (NKA) activity is downregulated and phosphoinositide metabolism is upregulated. We examined the effects of AGEs on NKA activity in porcine LLC-PK1 and human HK2 proximal tubule epithelial cells. AGE-BSA increased cellular phosphoinositol 4,5 bisphosphate (PIP2) production as determined by immunofluorescence microscopy and thin layer chromatography. AGE-BSA (40μM) induced3H-arachidonic acid release and reactive oxygen species (ROS) production via cytosolic phospholipase A2(cPLA2) activation. Within minutes, AGE-BSA significantly inhibited NKA surface expression and activity in a dose- and time-dependent manner as determined by immunofluorescence staining and [86Rb+] uptake, respectively, suggesting AGEs inhibit NKA by stimulating its endocytosis. The AGE-BSA-induced decrease in cell surface NKA was reversed by a cPLA2α inhibitor, neomycin, a PIP2 inhibitor, and PP2, a Src inhibitor. AGE-BSA increased binding of NKA to the α-adaptin but not β2- or μ2-adaptin subunits of the AP-2 clathrin pit adaptor complex. Transfection of HK2 cells with PIP5Kγ siRNA prevented AGE-BSA inhibition of NKA activity. AGEs may stimulate PIP5Kγ to increase PIP2 production, which may enhance AP-2 localisation to clathrin pits, increase clathrin pit formation, enhance NKA cargo recognition by AP-2 and/or stimulate cPLA2α activity. These results suggest AGEs modulate arachidonic acid and phosphoinositide metabolism to inhibit NKA via clathrin-mediated endocytosis. Elucidation of new intracellular AGE signaling pathways may lead to improved therapies for diabetic nephropathy.
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影响因子：
5.5
作者：
Liu, LJ;Mohammadi, K;Askari, A
通讯作者：
Askari, A
20-HETE 介导甲状旁腺激素和蛋白激酶 C 对肾磷酸盐转运的影响。
DOI：
10.1016/s0952-3278(98)90116-8
发表时间：
1998
期刊：
Prostaglandins, leukotrienes, and essential fatty acids
影响因子：
--
作者：
Silverstein,DM;Barac-Nieto,M;Falck,JR;Spitzer,A
通讯作者：
Spitzer,A
内皮素，完整肾小管上皮细胞中 Na( )-K( )-ATP 酶的肽抑制剂。
DOI：
10.1152/ajpcell.1989.257.6.c1101
发表时间：
1989
期刊：
The American journal of physiology
影响因子：
--
作者：
Zeidel,ML;Brady,HR;Kone,BC;Gullans,SR;Brenner,BM
通讯作者：
Brenner,BM
影响因子：
56.9
作者：
BROWNLEE, M;VLASSARA, H;CERAMI, A
通讯作者：
CERAMI, A
监督膜游泳：小型 G 蛋白救生员调节 PIPK 信号传导并监测细胞内 PtdIns(4,5)P2 库。
DOI：
10.1042/bj20060565
发表时间：
2006
期刊：
The Biochemical journal.
影响因子：
--
作者：
Santarius,Megan;Lee,ChangHo;Anderson,RichardA
通讯作者：
Anderson,RichardA