Tang W, Ziboh V A
Department of Dermatology, School of Medicine, University of California, Davis 95616.
Arch Dermatol Res. 1988;280(5):286-92. doi: 10.1007/BF00440602.
This study probes the extent of coupling between the reversal of epidermal hyperproliferation induced by essential fatty acid (EFA) deficiency in guinea pigs, the hydrolysis of epidermal phosphatidylinositol 4,5-bisphosphate (PtdIns4,5P2), and the rapid formation of inositol triphosphate (InsP3). Our data revealed that the incorporation of free [3H]-inositol into phosphatidylinositol 4P and PtdIns4,5P2 of microsomal preparations from hyperproliferative epidermis was markedly elevated when compared with epidermis from normal-fed animals. The reversal of the hyperproliferating epidermis by dietary cross-over supplementations with safflower oil and primrose oil resulted in striking morphological normalization, cellular decrease in epidermal DNA synthesis, decrease in the biosynthesis of 14C-PtdIn4,5P2 from precursor 14C-inositol, and a significant increase in the rapid generation of transient InsP3 by epidermis from the cross-over-fed animals. These findings taken together indicate that the reversal of epidermal hyperproliferation to normal in guinea pig skin and the increased capability of the tissue microsomal preparation to generate InsP3 are linked in this tissue, and raise the possibility that epidermal inositol-phospholipid metabolism may play a role in the pathogenesis of cutaneous hyperproliferative disorders.
本研究探讨了豚鼠必需脂肪酸（EFA）缺乏诱导的表皮过度增殖逆转、表皮磷脂酰肌醇4,5-二磷酸（PtdIns4,5P2）水解以及肌醇三磷酸（InsP3）快速形成之间的偶联程度。我们的数据显示，与正常喂养动物的表皮相比，来自过度增殖表皮的微粒体制剂中游离[3H]-肌醇掺入磷脂酰肌醇4P和PtdIns4,5P2的量显著升高。通过用红花油和月见草油进行饮食交叉补充来逆转过度增殖的表皮，导致显著的形态学正常化、表皮DNA合成的细胞减少、前体14C-肌醇合成14C-PtdIn4,5P2的生物合成减少，以及交叉喂养动物的表皮快速产生瞬时InsP3的能力显著增加。这些发现共同表明，豚鼠皮肤中表皮过度增殖向正常的逆转与组织微粒体制剂产生InsP3的能力增加在该组织中是相关联的，并提出表皮肌醇磷脂代谢可能在皮肤过度增殖性疾病的发病机制中起作用的可能性。
