Analysis of Abnormal Expression of Sphingomyelin Acylase in Atopic Dermatitis. Resulting in Ceramide Deficiency

特应性皮炎中鞘磷脂酰化酶的异常表达分析。

• 批准号: 07457192
• 负责人: KAWASHIMA Makoto
• 金额: $ 2.69万
• 依托单位: TOKYO WOMEN'S MEDICAL COLLEGE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457192/
• 关键词: Atopic Dermatitis; Ceramide; Sphingomyelin; Sphingomyelinase; Sphingomyelin acylase; スフィンゴシルホスホリルコリン; アトピー性皮膚炎; アシラーゼ

Previously, we demonstrated that there is a marked reduction in the amount of ceramide in the stratum corneum of both lesional and nonlesional forearms in atopic dermatitis(AD), suggesting that an insufficiency of ceramides in the stratum corneum is an etiologic factor in atopic dry and barrier-disrupted skin. In this study, we investigated, as a possible mechanism involved in the ceramide deficiency, whether sphingomyelin (SM) metabolism is altered in AD as compared to normal controls. In stripped stratum corneum and biopsied whole epidermis of patients with AD.SM hydrolysis as measured at pH4.7 using *choline-methyl-^<14>C* sphingomyelin as a substrate were markedly increased by 27-and 7-fold, respectively.Radio-thin-layr chromatography of the reaction products revealed that, whereas the SM hydrolysis in age-matched normal controls were associated with sphingomyelinase (SMase) that degrades SM to yield ceramides and phosphorylcholin (PC), most of the SM hydrolysis detected in AD were … More attributable not to the SMase but to a hitherto undiscovered epidermal enzyme. SM acylase, which releases free fatty acidand sphingosyl-PC (Sph-PS) instead of ceramides. The potential of this acylaselike enzyme to generate Sph-PC through SM hydrolysis was corroborated by thin-layr chromatographic analysis of the reaction products obtained using porcine kidney acylase, followed by high-perfomance liquid chromatography-mass spectrometry. Furthermore, Sph-PC was also detected by high-performance liquid chromatography-massspectrometry after incubation of SM with atopic stratum corneum samples. On the other hand, the stratum corneum of patients with contact dermatitis or chronic eczema exhibited neither increased SM hydrolysis nor the generation of Sph-PC upon radio-thin-layr chromatographic analysis. These findins suggest that SM metabolism is altered in AD,resulting in a decrease in levels of ceramides, which could be an etiologic factor in the continuous generation of atopic dry and barrier disrupted skin observed in AD. Less

先前，我们证明了特应性皮炎（AD）患者的病变和非病变前臂角质层中神经酰胺的数量明显减少，这表明角质层中神经酰胺的不足是特应性皮肤干燥和屏障破坏的一个病因。在这项研究中，我们研究了神经酰胺缺乏的可能机制，即与正常对照相比，AD患者鞘磷脂（SM）代谢是否发生了改变。阿尔茨海默病患者角质层剥脱及全表皮活检。在pH4.7下，使用*胆碱-甲基-^<14>C*鞘磷脂作为底物，SM的水解率分别显著提高了27倍和7倍。反应产物的放射性薄层色谱显示，在年龄匹配的正常对照中，SM水解与鞘磷脂酶（SMase）有关，SMase可降解SM生成神经酰胺和磷酸胆碱（PC），而在AD中检测到的大部分SM水解更可能归因于一种迄今为止未发现的表皮酶，而不是SMase。SM酰化酶，释放游离脂肪酸和鞘氨酰- pc （Sph-PS）代替神经酰胺。利用猪肾酰化酶对反应产物进行薄层色谱分析和高效液相色谱-质谱分析，证实了该酶通过SM水解生成Sph-PC的潜力。此外，SM与特应性角质层样品孵育后，采用高效液相色谱-质谱法检测了Sph-PC。另一方面，接触性皮炎或慢性湿疹患者的角质层既没有增加SM水解，也没有产生Sph-PC。这些发现表明，SM代谢在AD中发生改变，导致神经酰胺水平下降，这可能是AD中观察到的特应性皮肤干燥和屏障破坏持续产生的病因因素。少

项目成果

Murata Yasuko: "Abnormal Expression of Sphingomyelin Acylase in Atopic Dermatitis:An Etiologic Factor for Ceramids Deficiency?" Journal of Investigative Dermatology. 106. 1242-1249 (1996)

Murata Yasuko：“特应性皮炎中鞘磷脂酰化酶的异常表达：神经酰胺缺乏的病因？”

Murata Yasuko: "Abnormal Expression of Sphingomyelin Acylase in Atopic-Dermatitis ; An Etiologic Factor for Ceramide" Journal of Investigatire Dermatology. 106. 1242-1249 (1996)

Murata Yasuko：“特应性皮炎中鞘磷脂酰化酶的异常表达；神经酰胺的病因”《皮肤病学研究杂志》。

Murata Yasuko: "Abnormal Expression of Sphingomyerin Acylase Atopic Dermatology." Journal of Investigative Dermatology. 106. 1242-1249 (1996)

Murata Yasuko：“鞘磷脂酰化酶特应性皮肤病的异常表达。”

川島眞: "アトピー皮膚と香粧品科学" 日本香粧品科学会誌. 20. 270-272 (1996)

Makoto Kawashima：“特应性皮肤和化妆品科学”日本化妆品学会杂志 20. 270-272 (1996)。

Kawashima Makoto: "Atopic dermatitis and cosmetic science." Journal of Japanese Cosmetic Science Society. 20. 270-272 (1996)

川岛诚：“特应性皮炎与美容科学。”