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首页> 外文期刊>Journal of Cellular Physiology >Vitamin A metabolism in benign and malignant melanocytic skin cells: importance of lecithin/retinol acyltransferase and RPE65.
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Vitamin A metabolism in benign and malignant melanocytic skin cells: importance of lecithin/retinol acyltransferase and RPE65.

机译:维生素A代谢在良性和恶性的melanocytic皮肤细胞:的重要性卵磷脂/视黄醇酰基转移酶和RPE65。

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摘要

Disturbance in vitamin A metabolism seems to be an important attribute of cancer cells. Retinoids, particularly retinoic acid, have critical regulatory functions and appear to modulate tumor development and progression. The key step of vitamin A metabolism is the esterification of all-trans retinol, catalyzed by lecithin/retinol acyltransferase (LRAT). In this work, we show that malignant melanoma cells are able to esterify all-trans retinol and subsequently isomerize all-trans retinyl esters (RE) into 11-cis retinol, whereas their benign counterparts-melanocytes are not able to catalyze these reactions. Besides, melanoma cell lines express lecithin/retinol acyltranseferase both at the mRNA and protein levels. In contrast, melanocytes do not express this enzyme at the protein level, but mRNA of lecithin/retinol acyltransefrase could still be present at mRNA level. RPE65 is expressed in both melanocytic counterparts, and could be involved in the subsequent isomerization of RE produced by lecithin/retinol acyltransefrase to 11-cis retinol. Cellular retinol-binding protein 2 does not appear to be involved in the regulation of all-trans retinol esterification in these cells. Expression of LRAT and RPE65 can be modulated by retinoids. We propose that the post-transcriptional regulation of lecithin/retinol acyltransefrase could be involved in the differential expression of this enzyme. Besides, activities of LRAT and RPE65 may be important for removal of all-trans retinal which is the substrate for retinoic acid production in skin cells. Consequently, the decreasing cellular amount of retinoic acid and its precursor molecules could result in a change of gene regulation.
机译:在维生素代谢似乎是一种干扰癌细胞的重要属性。特别是视黄酸,至关重要监管职能,调节肿瘤开发和发展。维生素A新陈代谢的酯化all-trans视黄醇,催化卵磷脂/视黄醇酰基转移酶(LRAT)。恶性黑色素瘤细胞能够酯化all-trans视黄醇,随后异构化all-trans视黄基酯(重新)11-cis视黄醇,而他们的良性的counterparts-melanocytes不能催化这些反应。在表达卵磷脂/视黄醇acyltranseferase信使rna和蛋白质的水平。黑色素细胞不表达这种酶在蛋白质含量,但mRNA卵磷脂/视黄醇acyltransefrase仍然可以出席mRNA的水平。同行,可以参与随后的异构化生产的再保险卵磷脂/视黄醇acyltransefrase 11-cis视黄醇。没有参与的规定在这些细胞all-trans视黄醇酯化。表达LRAT和RPE65可以调制类维生素a。转录后调控卵磷脂/视黄醇acyltransefrase参与的微分表达式酶。对取消all-trans视网膜非常重要视黄酸的底物是什么生产的皮肤细胞。减少细胞的视黄酸量和它的前体分子可能导致改变的基因调控。

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