调节大鼠肝L-pyruvate由葡萄糖激酶促进剂组成和活动,n - 3多不饱和脂肪酸,过氧物酶体proliferator-activated receptor-alpha受体激动剂。
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徐J,基督教B,跳DB
调节大鼠肝L-pyruvate由葡萄糖激酶促进剂组成和活动,n - 3多不饱和脂肪酸,过氧物酶体proliferator-activated receptor-alpha受体激动剂。
生物化学杂志。2006年7月7日,281 (27):18351 - 62。Epub 2006年4月27日。
- PubMed ID
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16644726 (在PubMed]
- 文摘
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碳水化合物调节元件结合蛋白(ChREBP), MAX-like因子X (MLX)和肝核factor-4alpha (HNF-4alpha)是关键转录因子参与glucose-mediated诱导肝l型丙酮酸激酶(L-PK)基因转录。n - 3多不饱和脂肪酸(PUFA)和WY14643(过氧物酶体proliferator-activated受体α(PPARalpha)受体激动剂)干扰分子L-PK体内基因转录和鼠原发性肝细胞。喂养老鼠的饮食含有n - 3 PUFA或WY14643抑制肝mRNA (L-PK)但没有抑制肝ChREBP或HNF-4alpha核丰富。肝MLX核丰富,然而,由n - 3 PUFA但不是WY14643镇压。在大鼠原发性肝细胞,分子信使rna的积累(LPK)和L-PK子活动与增加ChREBP核丰富。这种治疗也增加了L-PK发起人入住率由RNA聚合酶II (RNA聚合酶II),乙酰化组蛋白H3 (Ac-H3)和乙酰化组蛋白H4 (Ac-H4)但没有显著影响L-PK发起人入住率ChREBP或HNF-4alpha。抑制L-PK启动子活性的n - 3 PUFA与抑制RNA聚合酶II, Ac-H3, Ac-H4入住率L-PK启动子。尽管n - 3 PUFA瞬变抑制ChREBP和MLX核丰富,这种治疗不影响ChREBP-LPK启动子相互作用。HNF4alpha-LPK启动子相互作用被n - 3 PUFA瞬变抑制。抑制L-PK WY14643活动发起人与瞬时下降ChREBP核丰度和减少Ac-H4交互L-PK启动子。 WY14643, however, had no impact on MLX nuclear abundance or HNF4alpha-LPK promoter interaction. Although overexpressed ChREBP or HNF-4alpha did not relieve n-3 PUFA suppression of L-PK gene expression, overexpressed MLX fully abrogated n-3 PUFA suppression of L-PK promoter activity and mRNA(L-PK) abundance. Overexpressed ChREBP, but not MLX, relieved the WY14643 inhibition of L-PK. In conclusion, n-3 PUFA and WY14643/PPARalpha target different transcription factors to control L-PK gene transcription. MLX, the heterodimer partner for ChREBP, has emerged as a novel target for n-3 PUFA regulation.