Arginine decreases peroxisome proliferator-activated receptor-γ activity via c-Jun.

Arginine decreases peroxisome proliferator-activated receptor-γ activity via c-Jun.
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精氨酸通过C-JUN降低过氧化物酶体增殖物激活的受体-γ活性。

DOI:
10.1007/s11010-011-1122-9
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发表时间:
2012-03
影响因子:
4.3
通讯作者:
Kozar, Rosemary A.
Kozar, Rosemary A.
中科院分区:
生物学3区
文献类型:
--
作者:
Ban, Kechen;Peng, Zhanglong;Lin, Wei;Kozar, Rosemary A.

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我们之前已经证明,在缺血后肠道中,肠内精氨酸通过 c-Jun/AP-1 增强损伤和炎症,并消除过氧化物酶体增殖物激活受体 (PPAR) γ 活性。在本研究中,我们在体外研究了精氨酸在大鼠小肠上皮IEC-6细胞中抑制PPARγ的机制。精氨酸以时间和剂量依赖性方式抑制 PPARγ 转录活性。此外,精氨酸对 PPARγ 的下调涉及 c-Jun 的磷酸化,该磷酸化发生在 PPARγ 转录活性变化之前。 c-Jun 的沉默使 PPARγ 的增加超过非沉默细胞的水平,并且精氨酸不会减轻这种影响。通过一系列阻断研究,我们发现精氨酸和 PPARγ 配体依赖性结合位点之间没有关系。总之,精氨酸降低了小肠肠上皮细胞中 PPARγ 的转录活性。这些变化部分归因于 c-Jun 的磷酸化,并且可以解释肠内精氨酸对缺血后肠道的有害影响。
We have previously shown in the post ischemic gut that enteral arginine enhanced injury and inflammation via c-Jun/ AP-1 and abrogated peroxisome proliferator-activated receptor (PPAR) γ activity. In the current study, we investigated the mechanism by which arginine inhibited PPARγ in vitro in rat small bowel epithelial IEC-6 cells. Arginine repressed PPARγ transcriptional activity in a time and dose dependent fashion. Furthermore, downregulation of PPARγ by arginine involved phosphorylation of c-Jun that occurred prior to changes in PPARγ transcriptional activity. Silencing of c-Jun increased PPARγ beyond that of nonsilenced cells and was not mitigated by arginine. Using a series of blocking studies, we found no relationship between arginine and the ligand-dependent binding site of PPARγ. In conclusion, arginine decreased PPARγ transcriptional activity in small bowel intestinal epithelial cells. These changes are due, in part, to phosphorylation of c-Jun and may explain the deleterious effects of enteral arginine in the post ischemic gut.
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