Oxidative lipidomics of γ-irradiation-induced intestinal injury
Oxidative lipidomics of γ-irradiation-induced intestinal injury
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DOI：
10.1016/j.freeradbiomed.2007.08.021
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发表时间：
2008-02-01
影响因子：
7.4
通讯作者：
Kagan, Valerian E.
中科院分区：
文献类型：
--
作者：
Tyurina, Yulia Y.;Tyurin, Vladimir A.;Kagan, Valerian E.
虽然γ射线诱导的组织损伤与脂质过氧化有关，但尚未确定单个磷脂分子靶点。我们采用氧化脂质组学定性和定量表征磷脂过氧化反应的放射敏感性组织，小肠，暴露于全身照射（TBI）（10和15戈伊）的小鼠。使用电喷雾电离质谱，我们发现，主要类别的肠磷脂-磷脂酰胆碱，磷脂酰乙醇胺，磷脂酰丝氨酸，磷脂酰肌醇，包括集群与高度氧化的分子物种含有二十二碳六烯酸。心磷脂的分子种类仅由两种主要的较不易氧化的个体分子种类-四亚油酸心磷脂和三亚油酰-单油酰心磷脂代表。选择性和强大的氧化的两个阴离子型磷脂-心磷脂在线粒体和磷脂酰丝氨酸外的磷脂-γ射线照射后24小时观察。MS分析检测到几种TBI诱导的氧化心磷脂分子种类：（C-18：2）3（C-18：2-OOH）、（C-18：2）（2）（C-18：2-OOH）（2）、（C-18：2）（1）（C-18：2_OOH）（3）和（C-18：2-OOH）（4）。参与TBI引发的磷脂酰丝氨酸过氧化反应的主要分子种类包括C-18：0/C-22：6-OOH、C-18：0/C-22：5-OOH和C-18.0/C-22：4-OOH。更丰富的磷脂-磷脂酰胆碱和磷脂酰乙醇胺-没有发现任何氧化应激反应，尽管存在高度氧化的二十二碳六烯脂肪酸残基在其分子物种。在γ射线照射的小鼠的肠中检测到的半胱天冬酶3/7的显著活化表明TBI损伤中涉及凋亡性细胞死亡。考虑到心磷脂和磷脂酰丝氨酸的氧化分子种类在体外不同细胞的凋亡过程中积累，我们推测心磷脂和磷脂酰丝氨酸氧化产物可能是有用的潜在生物标志物的γ-辐射诱导的肠道细胞凋亡在体内，并可能代表一个有前途的目标，发现新的辐射防护剂和辐射增敏剂。(c)2007爱思唯尔公司All rights reserved.
Although gamma-irradiation-induced tissue injury has been associated with lipid peroxidation, the individual phospholipid molecular targets have not been identified. We employed oxidative lipidomics to qualitatively and quantitatively characterize phospholipid peroxidation in a radiosensitive tissue, the small intestine, of mice exposed to total body irradiation (TBI) (10 and 15 Gy). Using electrospray ionization mass spectrometry we found that the major classes of intestine phospholipids-phosphatidylclioline, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol-included clusters with highly oxidizable molecular species containing docosahexaenoic fatty acid. Molecular species of cardiolipin were represented by only two major less oxidizable individual molecular species-tetralinoteoylcardiolipin and trilinoleoyl-mono-oleoylcardiolipin. Selective and robust oxidation of two anionic phospholipids-cardiolipin in mitochondria and phosphatidylserine outside of mitochondria-was observed 24 h after gamma-irradiation. MS analysis detected several TBI-induced molecular species of oxidized cardiolipin: (C-18:2)3(C-18:2-OOH), (C-18:2)(2)(C-18:2-OOH)(2), (C-18:2)(1)(C-18:2_OOH)(3), and (C-18:2-OOH)(4). The major molecular species involved in TBI-triggered peroxidation of phosphatidylserine included C-18:0/C-22:6-OOH, C-18:0/C-22:5-OOH, and C-18.0/C-22:4-OOH. More abundant phospholipids-phosphatidylcholine and phosphatidylethanolamine-did not reveal any oxidative stress responses despite the presence of highly oxidizable docosahexaenoic fatty acid residues in their molecular species. A marked activation of caspases 3/7 that was detected in the intestine of gamma-irradiated mice indicates the involvement of apoptotic cell death in the TBI injury. Given that oxidized molecular species of cardiolipin and phosphatidylserine accumulate during apoptosis of different cells in vitro we speculate that cardiolipin and phosphatidylserine oxidation products may be useful as potential biomarkers of gamma-irradiation-induced intestinal apoptosis in vivo and may represent a promising target for the discovery of new radioprotectors and radiosensitizers. (c) 2007 Elsevier Inc. All rights reserved.