Adrenergic regulation and diurnal rhythm of p38 mitogen-activated protein kinase phosphorylation in the rat pineal gland
Adrenergic regulation and diurnal rhythm of p38 mitogen-activated protein kinase phosphorylation in the rat pineal gland
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DOI：
10.1210/en.2004-0864
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发表时间：
2004-11-01
期刊：
影响因子：
4.8
通讯作者：
Ho, AK
中科院分区：
文献类型：
--
作者：
Chik, CL;Mackova, M;Ho, AK
在这项研究中，我们研究了肾上腺素和光神经调节p38 MAPK磷酸化在大鼠松果体。内源性神经递质去甲肾上腺素（NE）剂量依赖性地增加大鼠松果体细胞磷酸化MAPK激酶3/6（MKK 3/6）和p38 MAPK的水平。时程研究显示，MKK 3/6和p38 MAPK磷酸化逐渐增加，在NE刺激后1 - 2 h达到峰值，并持续4 h。在NE处理2小时和4小时的细胞中，哌唑嗪或普萘洛尔的加入减少了NE诱导的MKK 3/6和p38 MAPK磷酸化，表明α和β肾上腺素能受体参与了持续反应。然而，用双丁酰cAMP或离子霉素处理模拟NE诱导的MKK 3/6和p38 MAPK磷酸化，双丁酰cGMP或4 β-佛波醇12-肉豆蔻酸酯13-乙酸酯都没有效果。NE诱导的MKK 3/6和p38 MAPK磷酸化的增加被KT 5720（蛋白激酶A抑制剂）和KN 93（Ca 2 +/钙调蛋白依赖性激酶抑制剂）阻断，但不被KT 5823（蛋白激酶G抑制剂）或calphostin C（蛋白激酶C抑制剂）阻断。在12小时光照的光照方案下，在Zeitgeber时间18，大鼠松果体中MKK 3/6和p38 MAPK磷酸化增加。夜间增加的p38 MAPK磷酸化被阻断暴露于动物恒定的光和减少与普萘洛尔，β-肾上腺素能受体阻滞剂治疗。总之，我们的研究结果表明，p38 MAPK的激活是在大鼠松果体的光神经控制下，蛋白激酶A和细胞内Ca 2+信号通路参与NE调节p38 MAPK。
In this study, we investigated adrenergic and photoneural regulation of p38MAPK phosphorylation in the rat pineal gland. Norepinephrine (NE), the endogenous neurotransmitter, dose-dependently increased the levels of phosphorylated MAPK kinase 3/6 (MKK3/6) and p38MAPK in rat pinealocytes. Time-course studies showed a gradual increase in MKK3/6 and p38MAPK phosphorylation that peaked between 1 and 2 h and persisted for 4 h post NE stimulation. In cells treated with NE for 2 and 4 h, the inclusion of prazosin or propranolol reduced NE-induced MKK3/6 and p38MAPK phosphorylation, indicating involvement of both alpha- and beta-adrenergic receptors for the sustained response. Whereas treatment with dibutyryl cAMP or ionomycin mimicked the NE-induced MKK3/6 and p38MAPK phosphorylation, neither dibutyryl cGMP nor 4beta-phorbol 12-myristate 13-acetate had an effect. The NE-induced increase in MKK3/6 and p38MAPK phosphorylation was blocked by KT5720 (a protein kinase A inhibitor) and KN93 (a Ca2+/calmodulin- dependent kinase inhibitor), but not by KT5823 (a protein kinase G inhibitor) or calphostin C (a protein kinase C inhibitor). In animals housed under a lighting regimen with 12 h of light, MKK3/6 and p38MAPK phosphorylation increased in the rat pineal gland at zeitgeber time 18. The nocturnal increase in p38MAPK phosphorylation was blocked by exposing the animal to constant light and reduced by treatment with propranolol, a beta-adrenergic blocker. Together, our results indicate that activation of p38MAPK is under photoneural control in the rat pineal gland and that protein kinase A and intracellular Ca2+ signaling pathways are involved in NE regulation of p38MAPK.