Osmolyte strategy in human monocytes and macrophages:: Involvement of p38MAPK in hyperosmotic induction of betaine and myoinositol transporters
Osmolyte strategy in human monocytes and macrophages:: Involvement of p38MAPK in hyperosmotic induction of betaine and myoinositol transporters
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DOI：
10.1006/abbi.1998.0661
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发表时间：
1998-06-01
影响因子：
3.9
通讯作者：
Häussinger, D
中科院分区：
文献类型：
--
作者：
Denkert, C;Warskulat, U;Häussinger, D
甜菜碱和肌醇类人猿相容的有机渗透调节剂，由暴露于高渗介质的细胞特异性积累。最近已描述了相容性有机渗透剂在调节大鼠肝巨噬细胞免疫功能中的作用。本报告描述了人外周血单核细胞和人外周血来源的巨噬细胞中的渗透剂策略。高渗（405 mOsm）暴露于单核细胞和巨噬细胞后6 ~ 12 h内，甜菜碱/γ-氨基-正丁酸（GABA）转运体BGT-1和钠依赖性肌醇转运体SMIT的mRNA水平上调。无论是否通过添加NaCl（50 mM）或棉子糖（100 mM）诱导高渗透压，都会发生BGT-1和SMIT mRNA的诱导。甜菜碱（5 mM）抑制BGT-1以及SMIT mRNA的上调。高渗（405 mOsm）暴露后，甜菜碱和肌醇的摄取增加了10倍，相比，正常渗透压条件。低渗暴露导致甜菜碱和肌醇的快速流出。用p38 MAP激酶的特异性抑制剂吡啶基咪唑SE 203580（10 μ M）处理细胞，可抑制高渗引起的BGT-1和SMIT mRNA以及甜菜碱和肌醇摄取增加45- 70%。数据显示，人外周血单核细胞和人外周血衍生的巨噬细胞使用甜菜碱和肌醇是相容的有机渗透压剂，当暴露于渗透压应力和p38（MAPK）参与高渗诱导的上调渗透压转运蛋白BGT-1和SMIT。(C)北京：科学出版社.
Betaine and myoinositol ape compatible organic osmolytes which are specifically accumulated by cells exposed to hyperosmotic medium. A role for compatible organic osmolytes in the regulation of immune function for rat liver macrophages has been described recently. This report describes an osmolyte strategy in human peripheral blood monocytes and human peripheral blood-derived macrophages. Hyperosmotic (405 mOsm) exposure of monocytes and macrophages led to am upregulation of betaine/gamma-amino-n-butyric acid (GABA) transporter BGT-1 and sodium-dependent myoinositol transporter SMIT in mRNA levels within 6 to 12 h. Induction of BGT-1 and SMIT mRNA occurred regardless of whether hyperosmolarity was induced by addition of NaCl (50 mM) or raffinose (100 mM). Betaine (5 mM) inhibited upregulation of BGT-1 as well as SMIT mRNA. After hyperosmotic (405 mOsm) exposure uptake of betaine and myoinositol was increased up to 10-fold compared to normoosmotic conditions. Hypoosmotic exposure led to a rapid efflux of betaine and myoinositol. Treatment of cells with the pyridinyl imidazole SE 203580 (10 mu M), a specific inhibitor of p38 MAP kinase, inhibited the hyperosmolarity-induced increase in BGT-1 and SMIT mRNA as well as betaine and mycoinositol uptake by 45-70%. The data show that human peripheral blood monocytes and human peripheral blood-derived macrophages use betaine and myoinositol are compatible organic osmolytes when exposed to osmotic stress and that p38(MAPK) is involved in hyperosmolarity-induced upregulation of osmolyte transporters BGT-1 and SMIT. (C) 1998 Academic Press.