Price D M, Terriff D L, Chik C L, Ho A K
Department of Physiology, University of Alberta, 7-26 Medical Sciences Building, Edmonton, Alberta T6G 2H7, Canada.
Mol Cell Endocrinol. 2007 Jan 15;263(1-2):134-41. doi: 10.1016/j.mce.2006.09.009. Epub 2006 Oct 31.
We have previously shown that mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) is induced at night under the control of a photoneural system in the rat pineal gland. Because of the established roles of MAPKs, glucocorticoids and proteasome activity in regulating MKP-1 expression in other cell types, their relative contributions to MKP-1 regulation were investigated in rat pinealocytes. We found that neither inhibition of MAPKs nor treatment with dexamethasone affected norepinephrine-stimulated MKP-1 expression. In contrast, treatment with proteasome inhibitors increased norepinephrine-stimulated MKP-1 protein levels and abolished the decline in norepinephrine-stimulated MKP-1 protein levels caused by inhibition of transcription or translation, or blockade of alpha-adrenergic receptors. Taken together, our results indicate that in rat pinealocytes, the continuous and rapid turnover of MKP-1 protein allows for its rapid induction but is not sufficient to generate the sustained increase in MKP-1 expression post-adrenergic stimulation.
我们之前已经表明，丝裂原活化蛋白激酶（MAPK）磷酸酶-1（MKP-1）在大鼠松果体光神经调节系统的控制下于夜间被诱导。鉴于MAPKs、糖皮质激素和蛋白酶体活性在调节其他细胞类型中MKP-1表达方面已确定的作用，我们在大鼠松果体细胞中研究了它们对MKP-1调节的相对贡献。我们发现，抑制MAPKs或用地塞米松处理均不影响去甲肾上腺素刺激的MKP-1表达。相反，蛋白酶体抑制剂处理增加了去甲肾上腺素刺激的MKP-1蛋白水平，并消除了由于转录或翻译抑制或α-肾上腺素能受体阻断而导致的去甲肾上腺素刺激的MKP-1蛋白水平下降。综上所述，我们的结果表明，在大鼠松果体细胞中，MKP-1蛋白持续且快速的周转使其能够快速诱导，但不足以在肾上腺素能刺激后产生MKP-1表达的持续增加。
