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A Protective Role for Triacylglycerols during Apoptosis

机译：细胞凋亡期间三酰基甘油的保护作用

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摘要

Triacylglycerols (TAGs) are one of the major constituents of the glycerolipid family. Their main role in cells is to store excess fatty acids, and they are mostly found within lipid droplets. TAGs contain acyl chains that vary in length and degree of unsaturation, resulting in hundreds of chemically distinct species. We have previously reported that TAGs containing polyunsaturated fatty acyl chains (PUFA-TAGs) accumulate via activation of diacylglycerol acyltransferases during apoptosis. In this work, we show that accumulation of PUFA-TAGs is a general phenomenon during this process. We further show that the accumulated PUFA-TAGs are stored in lipid droplets. Because membrane-residing PUFA phospholipids can undergo oxidation and form reactive species under increased levels of oxidative stress, we hypothesized that incorporation of PUFAs into PUFA-TAGs and their localization within lipid droplets during apoptosis limit the toxicity during this process. Indeed, exogenous delivery of a polyunsaturated fatty acid resulted in a profound accumulation of PUFA phospholipids and rendered cells more sensitive to oxidative stress, causing reduced viability. Overall, our results support the concept that activation of TAG biosynthesis protects cells from lipid peroxide-induced membrane damage under increased levels of oxidative stress during apoptosis. As such, targeting triacylglycerol biosynthesis in cancer cells might represent a new approach to promoting cell death during apoptosis.
机译：三酰基甘油（标签）是甘油脂素家族的主要成分之一。它们在细胞中的主要作用是储存过量的脂肪酸，并且它们主要在脂质液滴内发现。标签含有酰基链，其长度和不饱和度变化，导致数百种化学截然不同的物种。此前，我们先前已经报道了含有多不饱和脂肪酰基链（PUFA标签）的标签通过激活凋亡期间的二酰基甘油酰基转移酶积累。在这项工作中，我们表明PUFA标签的累积是在此过程中的一般现象。我们进一步表明，累积的PUFA标签存储在脂质液滴中。因为膜迁移磷脂可以在氧化应激水平提高的氧化胁迫水平下进行氧化并形成反应性物质，所以假设在凋亡期间，在凋亡期间脂质液滴中的脂质液滴内掺入PUFA标签中并在该过程中的脂肪液滴中的定位。实际上，多不饱和脂肪酸的外源递送导致PUFA磷脂的深远积累，并使细胞更敏感对氧化应激，导致降低的活力。总体而言，我们的结果支持标签生物合成的激活保护细胞免受脂质过氧化物诱导的膜损伤在细胞凋亡的提高水平下保护细胞。因此，靶向癌细胞中的三酰基甘油生物合成可能代表促进细胞凋亡期间促进细胞死亡的新方法。

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  • 来源
    《Biochemistry》 |2018年第1期|共9页
  • 作者

    Nasi Li; Yasemin Sancak; Jonna Frasor; G. Ekin Atilla-Gokcumen;

  • 作者单位

    Department of Chemistry University at Buffalo The State University of New York (SUNY) Buffalo New York 14260 United States;

    Department of Pharmacology University of Washington Seattle Washington 98195 United States;

    Department of Physiology and Biophysics University of Illinois at Chicago Chicago Illinois 60612 United States;

    Department of Chemistry University at Buffalo The State University of New York (SUNY) Buffalo New York 14260 United States;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
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