A role for protein kinases in the growth hormone regulation of cytochrome P4502C12 and insulin-like growth factor-I messenger RNA expression in primary adult rat hepatocytes.
A role for protein kinases in the growth hormone regulation of cytochrome P4502C12 and insulin-like growth factor-I messenger RNA expression in primary adult rat hepatocytes.
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蛋白激酶在原代成年大鼠肝细胞中细胞色素 P4502C12 和胰岛素样生长因子-I 信使 RNA 表达的生长激素调节中的作用。
作者：
Petra Toilet;C. Legraverend;Jan;A. Mode
GH是大鼠肝脏细胞色素P4502 C12和胰岛素样生长因子-I（IGF-I）mRNA表达的主要决定因素。在本研究中，蛋白激酶C（PKC）在GH介导的调节这两个基因的可能作用进行了研究。牛生长激素（bGH）培养的原代成年大鼠肝细胞导致二酰甘油的形成和随后的诱导P4502 C12和IGF-I mRNA，表明PKC依赖的信号转导。然而，刺激PKC的佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）或sn-1，2-二辛酰甘油治疗，在剂量和时间过程实验中，在存在或不存在的离子霉素，未能诱导P4502 C12或IGF-I mRNA。另一方面，通过PMA处理，即24 h预处理，下调PKC，减弱了P4502 C12和IGF-I mRNA的bGH诱导。100纳摩尔PMA可降低bGH刺激的IGF-I mRNA和P4502 C12 mRNA的表达（约50%）。与bGH组合的强效激酶抑制剂星形孢菌素治疗引起bGH反应的剂量依赖性降低，对不同mRNA种类的抑制剂具有不同的敏感性，IGF-I不太敏感。这些数据表明PKC在GH介导的P4502 C12和IGF-I mRNA的诱导中起允许作用。当蛋白激酶A的激活剂，如毛喉素和8-Br-cAMP加入到培养基中时，观察到对P4502 C12和IGF-I的mRNA水平的相反作用。（250字处删节）
GH is a major determinant of cytochrome P4502C12 and insulin-like growth factor-I (IGF-I) mRNA expression in rat liver. In the present study, a possible role for protein kinase C (PKC) in the GH-mediated regulation of these two genes was investigated. Addition of bovine GH (bGH) to cultured primary adult rat hepatocytes lead to the formation of diacylglycerol and subsequent induction of P4502C12 and IGF-I mRNA, indicating a PKC-dependent signal transduction. However, stimulation of PKC by phorbol 12-myristate 13-acetate (PMA) or sn-1,2-dioctanoylglycerol treatment, in dose and time-course experiments in the presence or absence of ionomycin, failed to induce either P4502C12 or IGF-I mRNA. On the other hand, down-regulation of PKC by PMA treatment, i.e. 24 h pretreatment, attenuated the bGH induction of both P4502C12 and IGF-I mRNA. One hundred nanomolar PMA reduced the bGH-stimulated expression of both IGF-I mRNA and P4502C12 mRNA (approximately 50%). Treatment with the potent kinase inhibitor staurosporine in combination with bGH caused a dose-dependent decrease of the bGH response with different sensitivities toward the inhibitor for the different mRNA species, IGF-I being less sensitive. These data indicate a permissive role for PKC in the GH-mediated induction of P4502C12 and IGF-I mRNA. When activators of protein kinase A, such as forskolin and 8-Br-cAMP were added to the culture medium opposite effects were observed on the mRNA levels of P4502C12 and IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)
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DOI：
--
发表时间：
1985
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Davis,RJ;Ganong,BR;Bell,RM;Czech,MP
通讯作者：
Czech,MP
展示多种 GH 反应性细胞类型中生长激素 (GH) 受体相关的酪氨酸激酶活性。
影响因子：
4.8
作者：
Stred,SE;Stubbart,JR;Argetsinger,LS;Shafer,JA;Carter-Su,C
通讯作者：
Carter-Su,C
生长激素促进小鼠 3T3-F442A 成纤维细胞和脂肪细胞中生长激素受体的酪氨酰磷酸化。
影响因子：
2.9
作者：
Foster,CM;Shafer,JA;Rozsa,FW;Wang,XY;Lewis,SD;Renken,DA;Natale,JE;Schwartz,J;Carter-Su,C
通讯作者：
Carter-Su,C
在成年大鼠肝细胞的原代非增殖培养物中苯巴比妥刺激细胞色素 P-450 从头合成。
DOI：
10.1073/pnas.79.9.2922
发表时间：
1982
影响因子：
11.1
作者：
Newman,S;Guzelian,PS
通讯作者：
Guzelian,PS
生长激素激活犬肾近端管状基底外侧膜中的磷脂酶 C。
DOI：
10.1073/pnas.86.16.6363
发表时间：
1989
影响因子：
11.1
作者：
Rogers,SA;Hammerman,MR
通讯作者：
Hammerman,MR