A study on altered expression of serine palmitoyltransferase and ceramidase in psoriatic skin lesion.

A study on altered expression of serine palmitoyltransferase and ceramidase in psoriatic skin lesion.
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DOI:
10.3346/jkms.2007.22.5.862
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发表时间:
2007-10
影响因子:
4.5
通讯作者:
Kim NI
Kim NI
中科院分区:
医学4区
文献类型:
--
作者:
Hong KK;Cho HR;Ju WC;Cho Y;Kim NI

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神经酰胺是维持角质层层状结构的主要脂质成分,也是调节细胞增殖和/或凋亡的脂质第二信使。在我们以前的研究中,银屑病皮损中神经酰胺和信号分子,特别是蛋白激酶C-α(PKC-α)和c-jun N-末端激酶(JNK)的水平与银屑病面积和严重程度指数(PASI)评分成比例地显著降低,这表明神经酰胺的缺失是通过下调促凋亡信号级联如PKC-α和JNK导致银屑病表皮过度增殖的原因。在这项研究中,我们研究了丝氨酸棕榈酰转移酶(SPT)和神经酰胺酶,两个主要的神经酰胺代谢酶,在银屑病表皮和非皮损表皮的蛋白表达。神经酰胺生成酶SPT在银屑病皮损表皮中的表达明显低于非皮损表皮,且与PASI评分呈负相关。而神经酰胺降解酶神经酰胺酶的表达在银屑病患者皮损表皮和非皮损表皮中无明显差异。提示SPT蛋白表达降低是银屑病患者神经酰胺水平降低的重要原因之一。
Ceramides are the main lipid component maintaining the lamellae structure of stratum corneum, as well as lipid second messengers for the regulation of cellular proliferation and/or apoptosis. In our previous study, psoriatic skin lesions showed marked decreased levels of ceramides and signaling molecules, specially protein kinase C-alpha (PKC-α) and c-jun N-terminal kinase (JNK) in proportion to the psoriasis area and severity index (PASI) scores, which suggested that the depletion of ceramide is responsible for epidermal hyperproliferation of psoriasis via downregulation of proapoptotic signal cascade such as PKC-α and JNK. In this study, we investigated the protein expression of serine palmitoyltransferase (SPT) and ceramidase, two major ceramide metabolizing enzymes, in both psoriatic epidermis and non-lesional epidermis. The expression of SPT, the ceramide generating enzyme in the de novo synthesis in psoriatic epidermis, was significantly less than that of the non-lesional epidermis, which was inversely correlated with PASI score. However, the expression of ceramidase, the degradative enzyme of ceramides, showed no significant difference between the lesional epidermis and the non-lesional epidermis of psoriatic patients. This might suggest that decreased expression of SPT protein is one of the important causative factors for decreased ceramide levels in psoriasis.
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