Rossi M A, Fidale F, Garramone A, Esterbauer H, Dianzani M U
Department of Experimental Medicine and Oncology, University of Turin, Italy.
Biochem Pharmacol. 1990 Jun 1;39(11):1715-9. doi: 10.1016/0006-2952(90)90116-3.
The effects of some 4-hydroxyalkenals, carbonylic products of lipid peroxidation, on hepatic phosphatidylinositol-4,5-bisphosphate (PIP2)-phospholipase C (PL-C) activity were investigated. The enzymatic activity was assayed in vitro by measuring the hydrolysis of [3H]PIP2 added as exogenous substrate to liver membranes. 4-Hydroxyhexenal (HEE), 4-hydroxyoctenal (HOE) and 4-hydroxynonenal (HNE) were able to stimulate both the basal and the GTPgammaS induced PL-C activity, whereas 4-hydroxyundecenal was inactive. HOE was the most active compound, being able to accelerate PIP2 breakdown at concentrations between 10(-12) and 10(-6) M, while in the case of HEE the effective doses ranged from 10(-11) to 10(-7) M and from 10(-9) to 10(-6) M in the case of HNE. 4-Hydroxynonenal was able to increase also bombesin stimulated PL-C activity. As these aldehydes accelerated PIP2 breakdown at doses which can be actually reached in tissues, the effects shown in vitro are likely to occur in vivo.
研究了一些脂质过氧化羰基产物4-羟基烯醛对肝脏磷脂酰肌醇-4,5-二磷酸（PIP2）-磷脂酶C（PL-C）活性的影响。通过测量作为外源性底物添加到肝细胞膜中的[3H]PIP2的水解来体外测定酶活性。4-羟基己烯醛（HEE）、4-羟基辛烯醛（HOE）和4-羟基壬烯醛（HNE）能够刺激基础和GTPγS诱导的PL-C活性，而4-羟基十一碳烯醛则无活性。HOE是最具活性的化合物，能够在10^(-12)至10^(-6) M的浓度范围内加速PIP2的分解，而HEE的有效剂量范围为10^(-11)至10^(-7) M，HNE的有效剂量范围为10^(-9)至10^(-6) M。4-羟基壬烯醛还能够增加蛙皮素刺激的PL-C活性。由于这些醛类在组织中实际能够达到的剂量下加速了PIP2的分解，因此体外显示的效应可能在体内发生。
