Multiple and additive functions of ALDH3A1 and ALDH1A1 - Cataract phenotype and ocular oxidative damage in Aldh3a1(-/-)/Aldh1a1(-/-) knock-out mice
Multiple and additive functions of ALDH3A1 and ALDH1A1 - Cataract phenotype and ocular oxidative damage in Aldh3a1(-/-)/Aldh1a1(-/-) knock-out mice
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DOI：
10.1074/jbc.m702076200
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发表时间：
2007-08-31
影响因子：
4.8
通讯作者：
Vasiliou, Vasilis
中科院分区：
文献类型：
--
作者：
Lassen, Natalie;Bateman, J. Bronwyn;Vasiliou, Vasilis
ALDH 3A 1（醛脱氢酶3A 1）在小鼠角膜中丰富，但在透镜中检测不到，并且ALDH 1A 1在角膜和透镜中以较低（催化）水平存在。为了检验ALDH 3A 1和ALDH 1A 1保护眼前段免受环境诱导的氧化损伤的假设，评价了Aldh 1a 1（-/ -）/Aldh 3a 1（-/ -）双敲除和Aldh 1a 1（-/-）和Aldh 3a 1（-/-）单敲除小鼠的生化变化和白内障形成（透镜混浊）。Aldh 1a 1/Aldh 3a 1-和Aldh 3a 1- null小鼠在1个月龄时在前和后囊下区域以及皮质中的点状混浊中发展白内障。Aldh 1a 1基因缺失的小鼠在生命后期（6 - 9个月大）也会患上白内障。暴露于UVB的1至3个月大的Aldh-null小鼠表现出加速的前透镜囊下混浊，与Aldh 1a 1（-/-）和野生型动物相比，Aldh 3a 1（-/-）和Aldh 3a 1（-/-）/Aldh 1a 1（-/-）小鼠中的混浊更为明显。白内障的形成与蛋白酶体活性降低、蛋白质氧化增加、GSH水平升高以及4-羟基-2-壬烯醛和丙二醛-蛋白加合物水平升高有关。总之，这些发现支持了角膜ALDH 3A 1和透镜ALDH 1A 1通过非酶（滤光）和酶（解毒）功能保护眼睛免受白内障形成的假设。
ALDH3A1 ( aldehyde dehydrogenase 3A1) is abundant in the mouse cornea but undetectable in the lens, and ALDH1A1 is present at lower ( catalytic) levels in the cornea and lens. To test the hypothesis that ALDH3A1 and ALDH1A1 protect the anterior segment of the eye against environmentally induced oxidative damage, Aldh1a1(-/ -)/Aldh3a1( -/ -) double knock-out and Aldh1a1(-/-) and Aldh3a1(-/-) single knock-out mice were evaluated for biochemical changes and cataract formation ( lens opacification). The Aldh1a1/ Aldh3a1- and Aldh3a1- null mice develop cataracts in the anterior and posterior subcapsular regions as well as punctate opacities in the cortex by 1 month of age. The Aldh1a1-null mice also develop cataracts later in life ( 6 - 9 months of age). One-to three-month-old Aldh-null mice exposed to UVB exhibited accelerated anterior lens subcapsular opacification, which was more pronounced in Aldh3a1(-/-) and Aldh3a1(-/-)/ Aldh1a1(-/-) mice compared with Aldh1a1(-/-) and wild type animals. Cataract formation was associated with decreased proteasomal activity, increased protein oxidation, increased GSH levels, and increased levels of 4-hydroxy-2-nonenal- and malondialdehyde-protein adducts. In conclusion, these findings support the hypothesis that corneal ALDH3A1 and lens ALDH1A1 protect the eye against cataract formation via nonenzymatic ( light filtering) and enzymatic ( detoxification) functions.