In vivo regulation of MAP kinases in Ratus norvegicus renal papilla by water loading and restriction.
In vivo regulation of MAP kinases in Ratus norvegicus renal papilla by water loading and restriction.
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通过水加载和限制对褐鼠肾乳头中 MAP 激酶的体内调节。
DOI：
10.1172/jci4384
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Berl,T
中科院分区：
文献类型：
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作者：
Wojtaszek,PA;Heasley,LE;Berl,T
在培养的肾细胞中，高渗性激活多种丝裂原活化蛋白激酶（MAPKs）并增强热休克蛋白（HSPs）的表达。在大鼠中，24小时限水使平均尿渗透压（Uosm）从2,179 +/-153 mOsm/kg增加到2,944+/-294 mOsm/kg (P < 0.001)，并与c-Jun nh2末端蛋白激酶（JNK）的乳头活性显著（P < 0.05）增加22%，细胞外信号调节蛋白激酶（ERK）增加49%，p38 MAPK增加15%相关。相反，24 h水负荷（Uosm 473+/-33 mOsm/kg）导致JNK活性降低43% (P < 0.001)， ERK活性降低39% (P < 0.05)， p38 MAPK活性降低26% （P < 0.05）。在等渗皮层中没有观察到这种调制。与对照组相比，满载水的大鼠乳头中的c-Jun磷酸化降低了45%。高渗乳头中hsp110、诱导型hsp70和hsp25的表达量高于等渗皮层，但不受动物水合状态的影响。在培养的髓内集管细胞中，HSP在500 mOsm/kg时表达量最大，JNK的激活量持续增加。我们得出结论，在基本水合条件下，这些热休克蛋白在高渗的内髓质中表达最多，而MAPK家族的所有三个成员的激活都接近但不是最大的。
In cultured renal cells, hypertonicity activates multiple mitogen-activated protein kinases (MAPKs) and enhances the expression of heat shock proteins (HSPs). In rats, 24 h water restriction increased mean urinary osmolality (Uosm) from 2, 179+/-153 mOsm/kg to 2,944+/-294 mOsm/kg (P < 0.001) and was associated with significant (P < 0.05) increases in the papillary activity of c-Jun NH2-terminal protein kinase (JNK) by 22%, extracellular signal-regulated protein kinase (ERK) by 49%, and p38 MAPK by 15%. Conversely, 24 h of water-loading (Uosm 473+/-33 mOsm/kg) caused suppression of JNK activity by 43% (P < 0.001), ERK by 39% (P < 0.05), and p38 MAPK by 26% (P < 0.05). No such modulation was observed in the isotonic cortex. c-Jun phosphorylation was decreased in papilla from water-loaded rats by 45% versus controls. Expression of Hsp 110, inducible Hsp 70, and Hsp 25 was greater in the hyperosmotic papilla than the isosmotic cortex but was not affected by the animal's hydration state. In cultured inner medullary collecting duct cells, HSP expression was maximal at 500 mOsm/kg, while activation of JNK continued to increase. We conclude that under basal conditions of hydration, these HSPs are maximally expressed in the hypertonic inner medulla, while the activation of all three members of the MAPK family approaches but is not maximal.