J Korean Med Sci.  2007 Oct;22(5):862-867. 10.3346/jkms.2007.22.5.862.

A Study on Altered Expression of Serine Palmitoyltransferase and Ceramidase in Psoriatic Skin Lesion

• Hong KK
• Cho HR
• Ju WC
• Cho Y
• Kim NI

• KMID: 1713294
• DOI: http://doi.org/10.3346/jkms.2007.22.5.862

Abstract

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-alpha) 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-alpha 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.

Keyword

Serine C-Palmitoyltransferase; Ceramidase; Ceramides; Psoriasis

MeSH Terms

Adolescent
Adult
Amidohydrolases/*biosynthesis/metabolism
Apoptosis
Cell Proliferation
Ceramidases
Ceramides/chemistry
Child
Epidermis/metabolism
Female
Humans
JNK Mitogen-Activated Protein Kinases/metabolism
Male
Models, Biological
Protein Kinase C-alpha/metabolism
Psoriasis/*blood/diagnosis
Serine C-Palmitoyltransferase/*biosynthesis

Figure

• 

  Fig. 1 Western blot analysis of SPT in the lesional and the non-lesional epidermis of posriasis patients. Western blotting was performed using anti-SPT antibodies, as described in Materials and Method. The level of SPT expression was quantified by densitometry and is expressed as ratio of SPT and tubulin. *, significant differences between lesional epidermis and non-lesional epidermis (p<0.05).

• 

  Fig. 2 Western blot analysis of ceramidase in the lesional and the non-lesional epidermis of posriasis patients. Western blotting was performed using anti-ceramide antibodies, as described in the Materials and Method. The level of ceramidase expression was quantified by densitometry and is expressed as a ratio of ceramidase and tubulin. However, we could not find any statistically significant difference between two groups.

• 

  Fig. 3 (A) The mean ratio of SPT and tubulin of the lesional epidermis was significantly decreased compared to that of the non-lesional epidermis. *, significant differences between lesional epidermis and non-lesional epidermis (p<0.05). (B) However, there was no significant difference between the mean ratio of ceramidase to tubulin in the lesional epidermis and that of the non-lesional epidermis.

• 

  Fig. 4 Correlation between the percentage reduction in the ration of SPT/tubulin in the lesional epidermis and the PASI scores of psoriasis patients. A significant negative correlation was observed (Spearman's rho=-0.76, p=0.01).

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  Fig. 5 The synthesis of ceramide is regulated by several enzymes such as sphingomyelinase, β-glucocerebrosidase, and ceramidase. Also a de novo pathway mediated by serine palmitoyltransferase (SPT) functions as the key pathway of ceramide systhesis. SM, spingomyelin; SPT, serine palmitoyltransferase.

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