Huang Li, Grami Vahid, Marrero Yernan, Tang Daxin, Yappert Marta C, Rasi Vittorio, Borchman Douglas
Department of Ophthalmology and Visual Science, University of Louisville, 301 E. Mohammad Ali Boulevard, Louisville, KY 40202, USA.
Invest Ophthalmol Vis Sci. 2005 May;46(5):1682-9. doi: 10.1167/iovs.04-1155.
To determine the phospholipid changes responsible for the increase in membrane lipid hydrocarbon chain order, or stiffness, with age and cataract in the human lens.
Clear human lenses were pooled into four groups, with donors ranging in age from 15 to 29, 30 to 49, 50 to 64, and 65 to 74 years. Whole human cataractous lenses were obtained from donors after extracapsular cataract extraction. Cataractous lenses were grouped into four classifications: mature, mixed cortical and nuclear, immature nuclear sclerotic, mature posterior subcapsular, and mature nuclear. Lipids were extracted and quantified gravimetrically. The relative phospholipid composition was determined by (31)P-nuclear magnetic resonance spectroscopy.
The relative and absolute amount of sphingolipids, including dihydrosphingomyelin and sphingomyelin, increased with age, whereas glycerolipids, including phosphatidylcholine and two phosphatidylethanolamine-related phospholipids, decreased. These changes were exacerbated by the presence of cataract and were substantial, greater than the changes in lipid levels reported in any organ in association with any disease.
The changes in the amount of lipids with age and cataract support the idea that glycerolipids are selectively oxidized over lipids with fewer double bonds, such as sphingolipids. As a result of the elevation of sphingolipid levels with species, age, and cataract, lipid hydrocarbon chain order, or stiffness, increases. Increased membrane stiffness may increase light-scattering, reduce calcium pump activity, alter protein-lipid interactions, and perhaps slow fiber cell elongation.
确定导致人晶状体中膜脂质烃链有序性增加或硬度增加的磷脂变化,以及年龄和白内障对此的影响。
将透明的人晶状体分为四组,供体年龄范围分别为15至29岁、30至49岁、50至64岁和65至74岁。从白内障囊外摘除术后的供体获取完整的人白内障晶状体。白内障晶状体分为四类:成熟型、皮质和核混合型、未成熟核硬化型、成熟后囊下型和成熟核型。采用重量法提取并定量脂质。通过磷-31核磁共振波谱法测定相对磷脂组成。
包括二氢鞘磷脂和鞘磷脂在内的鞘脂的相对含量和绝对含量随年龄增长而增加,而包括磷脂酰胆碱和两种与磷脂酰乙醇胺相关的磷脂在内的甘油脂则减少。白内障的存在加剧了这些变化,且变化显著,大于与任何疾病相关的任何器官中报道的脂质水平变化。
脂质含量随年龄和白内障的变化支持以下观点,即甘油脂比双键较少的脂质(如鞘脂)更容易被选择性氧化。由于鞘脂水平随物种、年龄和白内障而升高,脂质烃链的有序性或硬度增加。膜硬度增加可能会增加光散射、降低钙泵活性、改变蛋白质-脂质相互作用,并可能减缓纤维细胞伸长。