Glycerophospholipid profile in oncogene-induced senescence
Glycerophospholipid profile in oncogene-induced senescence
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DOI：
10.1016/j.bbalip.2011.11.008
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发表时间：
2012-09-01
影响因子：
4.8
通讯作者：
Hengstler, Jan G.
中科院分区：
文献类型：
--
作者：
Cadenas, Cristina;Vosbeck, Sonja;Hengstler, Jan G.
脂质代谢和细胞膜脂质组成的改变与包括癌症在内的许多疾病的病理有关。然而，癌基因表达对细胞脂质谱的影响目前尚不清楚。在这项工作中，我们分析了在erbb2表达介导的过早衰老过程中诱导的脂质谱的变化。我们使用强力霉素诱导表达NeuT（一种致癌ERBB2变体）的MCF-7乳腺癌细胞作为模型系统。Affymetrix基因阵列数据显示，neut诱导了许多脂质代谢酶的转录改变，其中一些酶（ACSL3、CHPT1、PLD1、LIPG、MGLL、LDL和NPC1）可以通过实时定量PCR证实。一项通过高效液相色谱耦合傅立叶变换离子回旋共振质谱法获得的甘油磷脂和溶甘油磷脂谱的研究揭示了许多脂类（包括线粒体脂类）与衰老相关的变化。以PG（34:1）、PG（36:1）升高、LPE（18:1）、PG（40:7）、PI（36:1）降低最为显著。统计分析揭示了衰老时磷脂酰链缩短的总体趋势，以及磷脂酰甘油类中更饱和的酰基链的显著趋势。此外，衰老细胞的细胞胆固醇含量升高并积聚在液泡中。这些变化伴随着膜流动性的增加。在线粒体中，观察到膜电位的丧失以及细胞内分布的改变。总之，我们全面概述了衰老过程中胆固醇和甘油磷脂模式的改变，表明线粒体脂质主要受到影响，不易氧化的脂质种类增加。(C) 2011 Elsevier B.V.版权所有
Alterations in lipid metabolism and in the lipid composition of cellular membranes are linked to the pathology of numerous diseases including cancer. However, the influence of oncogene expression on cellular lipid profile is currently unknown. In this work we analyzed changes in lipid profiles that are induced in the course of ERBB2-expression mediated premature senescence. As a model system we used MCF-7 breast cancer cells with doxycycline-inducible expression of NeuT, an oncogenic ERBB2 variant. Affymetrix gene array data showed NeuT-induced alterations in the transcription of many enzymes involved in lipid metabolism, several of which (ACSL3, CHPT1, PLD1, LIPG, MGLL, LDL and NPC1) could be confirmed by quantitative realtime PCR. A study of the glycerophospholipid and lyso-glycerophospholipid profiles, obtained by high performance liquid chromatography coupled to Fourier-transform ion cyclotron resonance-mass spectrometry revealed senescence-associated changes in numerous lipid species, including mitochondrial lipids. The most prominent changes were found in PG(34:1), PG(36:1) (increased) and LPE(18:1), PG(40:7) and PI(36:1) (decreased). Statistical analysis revealed a general trend towards shortened phospholipid acyl chains in senescence and a significant trend to more saturated acyl chains in the class of phosphatidylglycerol. Additionally, the cellular cholesterol content was elevated and accumulated in vacuoles in senescent cells. These changes were accompanied by increased membrane fluidity. In mitochondria, loss of membrane potential along with altered intracellular distribution was observed. In conclusion, we present a comprehensive overview of altered cholesterol and glycerophospholipid pattems in senescence, showing that predominantly mitochondria' lipids are affected and lipid species less susceptible to peroxidation are increased. (C) 2011 Elsevier B.V. All rights reserved.