Concentration and distribution of ubiquinone (coenzyme Q), theendogenous lipid antioxidant, in the rat lens: effect of treatment withsimvastatin

[摘要] Purpose: Ubiquinone (Ub) is the only known endogenously synthesizedlipid soluble antioxidant. It is synthesized from intermediates in thecholesterol metabolic pathway. Our goal was to identify the Ubs anddetermine the concentration and distribution of Ubs in the rat lens andthe effect of treatment with simvastatin, a cholesterol synthesisinhibitor, on lens levels.Methods: Intact lenses and separated lens fractions from young ratswere homogenized in organic solvents, the Ubs recovered, and identifiedby HPLC analysis. Rats were fed Ub-10 to determine effects ofsupplementation on tissue levels. Sprague-Dawley (SD) and Chbb:Thom (CT)rats were treated with simvastatin, an inducer of cataracts in CT rats,to determine its effects on lens Ubs.Results: Ubiquinone-9 (9 isoprenes in its hydrocarbon tail) was themain Ub in the rat lens. The intact lens contained about 3.0 μg Ub/glens wet weight of which 80-90% was Ub-9 and the remainder Ub-10. Noreduced Ubs were detected. Although the epithelial fraction containedthe highest Ub concentration (about 8 μg/g), the cortex and nucleuscombined accounted for about 90% of the lens' total content. Dietarysupplementation with Ub-10 markedly increased the Ub-10 concentration inliver but not lens. Treatment with simvastatin decreased lens Ubs ofboth SD and CT rats by about 20%.Conclusions: The abundance of mitochondria in lens epithelium likelyaccounted for its high level of Ubs; but, finding most of the lens'total Ub in the cortex plus nucleus also suggests roles in maintainingthe fiber cell membrane. The decrease in lens Ubs caused by simvastatinis interpreted to reflect a response to drug induced cellular stressrather than to inhibition of the cholesterol synthesis pathway.

[学科分类] 生物化学/生物物理