Sphingolipid distribution changes with age in the human lens

被引:63
作者
Deeley, Jane M. [2 ]
Hankin, Joseph A. [3 ]
Friedrich, Michael G. [4 ]
Murphy, Robert C. [3 ]
Truscott, Roger J. W. [4 ]
Mitchell, Todd W. [1 ]
Blanksby, Stephen J. [2 ]
机构
[1] Univ Wollongong, Sch Hlth Sci, Wollongong, NSW, Australia
[2] Univ Wollongong, Sch Chem, Wollongong, NSW, Australia
[3] Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Aurora, CO USA
[4] Univ Sydney, Save Sight Inst, Sydney, NSW 2006, Australia
基金
美国国家卫生研究院; 澳大利亚研究理事会; 英国医学研究理事会;
关键词
cataract; MALDI imaging; sphingomyelin; dihydrosphingomyelin; phospholipid; ceramide; dihydroceramide; lipidomics; HUMAN CRYSTALLINE LENS; GLUTATHIONE-REDUCTASE; NUCLEAR CATARACT; SPHINGOMYELIN; OXIDATION; PROTEINS; GROWTH; WATER;
D O I
10.1194/jlr.M007716
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The formation of an internal barrier to the diffusion of small molecules in the lens during middle age is hypothesized to be a key event in the development of age-related nuclear (ARN) cataract. Changes in membrane lipids with age may be responsible. In this study, we investigated the effect of age on the distribution of sphingomyelins, the most abundant lens phospholipids. Human lens sections were initially analyzed by MALDI mass spectrometry imaging. A distinct annular distribution of the dihydrosphingomyelin, DHSM (d18:0/16:0), in the barrier region was observed in 64- and 70-year-old lenses but not in a 23-year-old lens. An increase in the dihydroceramide, DHCer (d18:0/16:0), in the lens nucleus was also observed in the older lenses. These findings were supported by ESI mass spectrometry analysis of lipid extracts from lenses dissected into outer, barrier, and nuclear regions. A subsequent analysis of 18 lenses ages 20-72 years revealed that sphingomyelin levels increased with age in the barrier region until reaching a plateau at approximately 40 years of age. Such changes in lipid composition will have a significant impact on the physical properties of the fiber cell membranes and may be associated with the formation of a barrier.-Deeley, J. M., J. A. Hankin, M. G. Friedrich, R. C. Murphy, R. J. W. Truscott, T. W. Mitchell, and S. J. Blanksby. Sphingolipid distribution changes with age in the human lens. J. Lipid Res. 2010. 51: 2753-2760.
引用
收藏
页码:2753 / 2760
页数:8
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