Induction of hepatocyte proliferation after partial hepatectomy is accompanied by a markedly reduced expression of phosphatidylethanolamine N-methyltransferase-2

Induction of hepatocyte proliferation after partial hepatectomy is accompanied by a markedly reduced expression of phosphatidylethanolamine N-methyltransferase-2
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DOI:
10.1016/s0005-2760(97)00011-8
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发表时间:
1997-05-17
期刊:
BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM
影响因子:
--
通讯作者:
Vance, DE
Vance, DE
中科院分区:
其他
文献类型:
--
作者:
Houweling, M;Cui, Z;Vance, DE

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磷脂酰乙醇胺N-甲基转移酶(PEMT)-2在大鼠肝癌细胞中的表达导致细胞分裂时间从18小时增加到50小时[Cui等(1994)J. Biol. Chem. 269,24531-24533]。我们研究了体内肝脏增殖是否存在类似的反比关系。因此,使用部分肝切除大鼠来研究PEMT 2在肝再生过程中的表达。部分肝切除术后磷脂酰胆碱的生物合成增强是由于CTP:磷酸胆碱胞苷酰转移酶的活性和量增加。另一方面,在大鼠肝再生的第一天,PEMT的总活性显着降低。在雄性和雌性大鼠中,部分肝切除术后24 h,总PEMT活性(45%)和PEMT 2蛋白损失(90%)的最大降低与最大DNA合成和CTP:磷酸胆碱胞苷酰转移酶活性一致。在雌性大鼠的饮食中补充饮食胆碱将这种模式从部分肝切除术后24小时转移到36小时,而雄性大鼠的模式不受影响。北方印迹分析表明,PEMT 2 mRNA的表达量相应减少,提示PEMT 2的表达量和活性在翻译前水平受到调控。因此,我们的数据显示CTP:磷酸胆碱胞苷酰转移酶和PEMT 2在再生大鼠肝脏的基因表达水平上的相互调节。这些结果暗示PEMT 2在生理学相关模型中参与肝细胞生长的调节。(C)1997年Elsevier Science B.V.
Expression of phosphatidylethanolamine N-methyltransferase (PEMT)-2 in rat hepatoma cells caused an increase in the time for cell division from 18 to 50 h [Cui et al. (1994) J. Biol. Chem. 269, 24531-24533]. We investigated whether or not a similar inverse relationship might exist for liver proliferation in vivo. Thus, partial hepatectomized rats were used to investigate the expression of PEMT2 during liver regeneration. Enhanced biosynthesis of phosphatidylcholine after partial hepatectomy was due to increased activity and amount of CTP:phosphocholine cytidylyltransferase. On the other hand the total activity of PEMT was markedly decreased during the first days of rat liver regeneration. Maximal decrease of total PEMT activity (45%) and loss of PEMT2 protein (90%) coincided with maximal DNA synthesis and CTP:phosphocholine cytidylyltransferase activity 24 h after partial hepatectomy in both male and female rats. Supplementing dietary choline in the diets of female rats shifted this pattern from 24 h to 36 h after partial hepatectomy, whereas the pattern in male rats was not affected. Northern blot studies showed that the amount of PEMT2 mRNA was decreased accordingly, suggesting regulation of the amount and activity of PEMT2 at a pre-translational level. Thus, our data show a reciprocal regulation of CTP:phosphocholine cytidylyltransferase and PEMT2 at the level of gene expression in regenerating rat liver. These results implicate PEMT2 in the regulation of hepatocyte cell growth in a physiologically relevant model. (C) 1997 Elsevier Science B.V.