Lipid peroxidation and cell cycle signaling: 4-hydroxynonenal, a key molecule in stress mediated signaling.
Lipid peroxidation and cell cycle signaling: 4-hydroxynonenal, a key molecule in stress mediated signaling.
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DOI：
10.18388/abp.2003_3689
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发表时间：
2003
影响因子：
1.7
通讯作者：
Yusong Yang;Rajendra K. Sharma;Abha Sharma;S. Awasthi;Y. Awasthi
中科院分区：
文献类型：
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作者：
Yusong Yang;Rajendra K. Sharma;Abha Sharma;S. Awasthi;Y. Awasthi
脂质过氧化产物，特别是4-羟基壬烯醛（4-HNE）在细胞周期信号转导中的作用越来越清楚。在这篇文章中，最近的研究表明，4-HNE在应激介导的信号转导细胞凋亡的重要作用进行了严格的评估。证据表明调制的紫外线，氧化应激和化学应激介导的细胞凋亡，通过阻断脂质过氧化的α-类谷胱甘肽S-转移酶（GST），这表明这些酶的重要作用，在保护免受氧化应激和应激介导的信号的脂质过氧化产物的作用。4-HNE代谢GST（mGSTA 4 -4、hGSTA 4 -4或hGST5.8）的过表达通过阻断JNK和半胱天冬酶活化来保护细胞免受4-HNE、氧化应激（H（2）O（2）或黄嘌呤/黄嘌呤氧化酶）和UV-A介导的凋亡，这表明4-HNE在由这些应激因子引起的凋亡机制中的作用。4-HNE的细胞内浓度似乎对细胞周期信号传导的性质至关重要，并且可能是分化、增殖、转化或凋亡信号传导的决定因素。4-HNE的细胞内浓度通过GST（GSTA 4 -4和hGST 5.8）的协调作用调节，GST将4-HNE缀合至GSH以形成缀合物（GS-HNE）和转运蛋白76 kDa Ral结合GT3活化蛋白（RLIP 76），其催化GS-HNE的ATP依赖性转运。由热、UV-A或H（2）O（2）引起的轻度应激对培养中的细胞没有明显影响，引起hGST 5.8和RLIP 76的快速、瞬时诱导。这些应激预处理的细胞获得代谢和排除4-HNE的能力，以加速的步伐，并获得相对抵抗凋亡的UV和氧化应激相比，未处理的对照细胞。通过用阻断GS-HNE转运的抗RLIP 76抗体包被细胞，可以消除应激预处理细胞的这种抗性。这些研究和以前的报告中讨论了这篇文章强烈建议的关键作用，4-HNE在应激介导的信号。
Role of lipid peroxidation products, particularly 4-hydroxynonenal (4-HNE) in cell cycle signaling is becoming increasingly clear. In this article, recent studies suggesting an important role of 4-HNE in stress mediated signaling for apoptosis are critically evaluated. Evidence demonstrating the modulation of UV, oxidative stress, and chemical stress mediated apoptosis by blocking lipid peroxidation by the alpha-class glutathione S-transferases (GSTs) is presented which suggest an important role of these enzymes in protection against oxidative stress and a role of lipid peroxidation products in stress mediated signaling. Overexpression of 4-HNE metabolizing GSTs (mGSTA4-4, hGSTA4-4, or hGST5.8) protects cells against 4-HNE, oxidative stress (H(2)O(2) or xanthine/xanthine oxidase), and UV-A mediated apoptosis by blocking JNK and caspase activation suggesting a role of 4-HNE in the mechanisms of apoptosis caused by these stress factors. The intracellular concentration of 4-HNE appears to be crucial for the nature of cell cycle signaling and may be a determinant for the signaling for differentiation, proliferation, transformation, or apoptosis. The intracellular concentrations of 4-HNE are regulated through a coordinated action of GSTs (GSTA4-4 and hGST5.8) which conjugate 4-HNE to GSH to form the conjugate (GS-HNE) and the transporter 76 kDa Ral-binding GTPase activating protein (RLIP76), which catalyze ATP-dependent transport of GS-HNE. A mild stress caused by heat, UV-A, or H(2)O(2)with no apparent effect on the cells in culture causes a rapid, transient induction of hGST5.8 and RLIP76. These stress preconditioned cells acquire ability to metabolize and exclude 4-HNE at an accelerated pace and acquire relative resistance to apoptosis by UV and oxidative stress as compared to unconditioned control cells. This resistance of stress preconditioned cells can be abrogated by coating the cells with anti-RLIP76 antibodies which block the transport of GS-HNE. These studies and previous reports discussed in this article strongly suggest a key role of 4-HNE in stress mediated signaling.