H2O2 and Src-dependent transactivation of the EGF receptor mediates the stimulatory effect of leptin on renal ERK and Na+, K+-ATPase
H2O2 and Src-dependent transactivation of the EGF receptor mediates the stimulatory effect of leptin on renal ERK and Na+, K+-ATPase
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DOI：
10.1016/j.peptides.2006.08.010
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发表时间：
2006-12-01
期刊：
影响因子：
3
通讯作者：
Marciniak, A.
中科院分区：
文献类型：
--
作者：
Bettowski, J.;Wojcicka, G.;Marciniak, A.
我们研究了瘦素增加大鼠肾脏中 Na+、K+-ATP 酶活性的机制。在麻醉下将瘦素注入肾动脉近端的腹主动脉，然后测量肾皮质和髓质中的Na+、K+-ATP酶活性。瘦素(1μg/kg·min)输注3小时后Na+、K+-ATP酶活性增加，同时伴随尿H2O2排泄和细胞外信号调节激酶(ERK)磷酸化水平的增加。瘦素对 ERK 和 Na+、K+-ATP 酶的作用被过氧化氢酶、表皮生长因子 (EGF) 受体特异性抑制剂 AG1478 和 PD158780 以及 ERK 抑制剂 PD98059 消除，并且被外源性 H2O2 和 EGF 模拟。 Src 酪氨酸激酶抑制剂 PP2 也可以阻止瘦素的作用。瘦素和 H2O2 增加了 Tyr(418) 处的 Src 磷酸化。我们得出结论，瘦素诱导的肾 Na+、K+-ATP 酶刺激涉及 H2O2 生成、Src 激酶、EGF 受体反式激活和 ERK 刺激。 (c) 2006 Elsevier Inc. 保留所有权利。
We examined the mechanism through which leptin increases Na+, K+-ATPase activity in the rat kidney. Leptin was infused under anaesthesia into the abdominal aorta proximally to the renal arteries and then Na+, K+-ATPase activity was measured in the renal cortex and medulla. Leptin (1 mu g/kg min) increased Na+, K+-ATPase activity after 3 h of infusion, which was accompanied by the increase in urinary H2O2 excretion and phosphorylation level of extracellular signal regulated kinase (ERK). The effect of leptin on ERK and Na+, K+-ATPase was abolished by catalase, specific inhibitors of epidermal growth factor (EGF) receptor, AG1478 and PD158780, as well as by ERK inhibitor, PD98059, and was mimicked by both exogenous H2O2 and EGF. The effect of leptin was also prevented by the inhibitor of Src tyrosine kinase, PP2. Leptin and H2O2 increased Src phosphorylation at Tyr(418). We conclude that leptin-induced stimulation of renal Na+, K+-ATPase involves H2O2 generation, Src kinase, transactivation of the EGF receptor, and stimulation of ERK. (c) 2006 Elsevier Inc. All rights reserved.