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首页> 外文期刊>Journal of cellular biochemistry. >Prostaglandin F2alpha induces the normoxic activation of the hypoxia-inducible factor-1 transcription factor in differentiating 3T3-L1 preadipocytes: Potential role in the regulation of adipogenesis.
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Prostaglandin F2alpha induces the normoxic activation of the hypoxia-inducible factor-1 transcription factor in differentiating 3T3-L1 preadipocytes: Potential role in the regulation of adipogenesis.

机译：前列腺素F2alpha在分化3T3-L1前脂肪细胞中诱导缺氧诱导因子1转录因子的正常氧化激活：在调控脂肪形成中的潜在作用。

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摘要

Prostaglandin F2alpha (PGF2alpha) is a potent paracrine inhibitor of adipocyte differentiation. Here we show that treatment of differentiating 3T3-L1 preadipocytes with PGF2alpha induces the expression of DEC1, a transcriptional repressor that has previously been implicated in the inhibition of adipogenesis in response to hypoxia as a downstream effector of the hypoxia-inducible factor-1 (HIF-1) transcription factor. Surprisingly, despite performing our experiments under normal ambient oxygen conditions, we find that treatment of differentiating 3T3-L1 preadipocytes with PGF2alpha also results in the marked activation of HIF-1, as measured by an increase in the accumulation of the HIF-1alpha regulatory subunit. However, unlike the effects of hypoxia, this PGF2alpha-induced normoxic increase in HIF-1alpha is not mediated by an increase in the stability of the HIF-1alpha polypeptide, rather we find that PGF2alpha selectively increases the expression of the alternatively spliced HIF-1alpha I.1 mRNA isoform. Significantly, we demonstrate that the shRNA-mediated knockdown of endogenous HIF-1alpha expression attenuates the PGF2alpha-induced expression of DEC1, overcomes the inhibitory effects of PGF2alpha on the expression of proadipogenic transcription factors C/EBPalpha and PPARgamma and partially rescues the PGF2alpha-induced inhibition of adipogenesis. Taken together, these results indicate that PGF2alpha promotes the activation of the HIF-1 transcription factor pathway under normal oxygen conditions, and highlight a potential role for the normoxic activation of the HIF-1/DEC1-pathway in mediating the inhibitory effects of PGF2alpha on adipocyte differentiation.
机译：前列腺素F2alpha（PGF2alpha）是脂肪细胞分化的有效旁分泌抑制剂。在这里，我们显示了用PGF2alpha治疗分化3T3-L1前脂肪细胞会诱导DEC1的表达，DEC1是一种转录抑制因子，以前曾参与抑制作为低氧诱导因子-1（HIF）下游效应的脂肪生成。 -1）转录因子。出乎意料的是，尽管我们在正常的环境氧气条件下进行了实验，但我们发现用PGF2alpha处理分化的3T3-L1前脂肪细胞也会导致HIF-1的活化，这是通过HIF-1alpha调节亚基积累的增加来衡量的。但是，与缺氧的影响不同，这种PGF2alpha诱导的HIF-1alpha正常氧增加不是通过HIF-1alpha多肽稳定性的增加来介导的，而是我们发现PGF2alpha选择性地增加了选择性剪接的HIF-1alpha的表达I.1 mRNA同工型。有意义的是，我们证明了shRNA介导的内源性HIF-1alpha表达的敲低减弱了PGF2alpha诱导的DEC1表达，克服了PGF2alpha对促脂肪转录因子C / EBPalpha和PPARgamma表达的抑制作用，并部分挽救了PGF2alpha诱导的抑制脂肪生成。综上所述，这些结果表明PGF2alpha在正常氧气条件下促进了HIF-1转录因子途径的激活，并突显了HIF-1 / DEC1途径的常氧激活在介导PGF2alpha对HIF的抑制作用中的潜在作用。脂肪细胞分化。

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