Circulating biologically active oxidized phospholipids show on-going and increased oxidative stress in older male mice.
Circulating biologically active oxidized phospholipids show on-going and increased oxidative stress in older male mice.
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DOI：
10.1016/j.redox.2012.11.011
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发表时间：
2013
期刊：
影响因子：
11.4
通讯作者：
McIntyre TM
中科院分区：
文献类型：
--
作者：
Liu J;Li W;Chen R;McIntyre TM
受到慢性乙醇摄入氧化应激的大鼠循环中，生物活性磷脂血小板激活因子（PAF）和化学氧化产生的氧化截短磷脂增加。循环炎症和凋亡磷脂可能与生理氧化应激相关。在老年小鼠和雄性小鼠的血浆中，PAF 和常见的氧化截短且具有生物活性的磷脂壬二酰磷脂酰胆碱 (Az-PC) 显着增加。 PAF 和 Az-PC 非常迅速地从循环中清除，不受年龄或性别的影响。暴露于Az-PC的血小板在其表面显示磷脂酰丝氨酸，并且随着年龄的增长，闭塞性血小板颈动脉血栓形成会加剧。生物活性磷脂在循环中各不相同，在老年雄性小鼠中含量最高。 PAF 和生物活性 Az-PC 的周转速度很快，并且不随年龄和性别而变化，因此产量的增加导致两种脂质的浓度和通量增加。血小板暴露于血浆 Az-PC 中，其线粒体去极化，增加促血栓形成的磷脂酰丝氨酸表达，并且老年小鼠中闭塞性血小板血栓形成增强。在常见的、温和的衰老氧化应激过程中，或在雄性动物中，与雌性动物相比，氧化修饰的磷脂在循环中增加。这些生物活性磷脂通过快速转运到肝脏和肾脏后的周转率没有变化，因此循环水平反映了产量的不断增加。 ► 氧化截短的磷脂在老年动物和雄性动物的循环中积聚。 ► 氧化截短的磷脂的清除既快速又恒定。 ► 循环氧化磷脂报告老年雄性小鼠存在持续的氧化应激。 ► 衰老会促进大血管中氧化剂引起的闭塞性血小板血栓形成。
The biologically active phospholipids Platelet-activating Factor (PAF) and oxidatively truncated phospholipids from chemical oxidation are increased in the circulation of rats subject to the oxidant stress of chronic ethanol ingestion. Potentially, circulating inflammatory and apoptotic phospholipids correlate to physiologic oxidative stress. PAF and the common oxidatively truncated and biologically active phospholipid azelaoyl phosphatidylcholine (Az-PC) were significantly increased in the plasma of older mice, and in male mice. PAF and Az-PC are very rapidly cleared from the circulation, which was unaffected by age or sex. Platelets exposed to Az-PC display phosphatidylserine on their surface, and occlusive platelet carotid arterial thrombosis is enhanced by aging. Biologically active phospholipids vary in the circulation, with the highest levels being found in older, male mice. Turnover of PAF and the biologically active Az-PC are rapid and are invariant with age and sex, so increased production accounts for the increased concentration and flux of both lipids. Platelets are exposed to plasma Az-PC that depolarizes their mitochondria to increase pro-thrombotic phosphatidylserine expression, and occlusive platelet thrombosis is enhanced in aged mice. Oxidatively modified phospholipids are increased in the circulation during common, mild oxidant stresses of aging, or in male compared to female animals. Turnover of these biologically active phospholipids by rapid transport into liver and kidney is unchanged, so circulating levels reflect continuously increased production. ► Oxidatively truncated phospholipids accumulate in the circulation of aged and male animals. ► Clearance of oxidatively truncated phospholipids is both rapid, and constant. ► Circulating oxidized phospholipids report continual oxidative stress in aged, male mice. ► Aging promotes oxidant-induced occlusive platelet thrombosis in large vessels.