Invited review articleA possible mechanism underlying the ceramide deficiency in atopic dermatitis: Expression of a deacylase enzyme that cleaves the N-acyl linkage of sphingomyelin and glucosylceramide
Section snippets
Discovery of SM-GCer deacylase
Ceramides constitute the core structures of several sphingolipids which play essential roles in cell proliferation and differentiation [1], [2], [3] and which have been implicated as inducers of programmed cell death [4]. In the epidermis, where ceramides are a major product of terminal differentiation, ceramides are an important determinant of the permeability barrier and water reservoir functions of the uppermost layer of epidermis, the stratum corneum [5], and they account for 50% of the
SM deacylase activity in AD
Since the ceramide content of the stratum corneum is regulated by a balance of the rate-limiting enzymes of sphingolipid base synthesis, including serine-palmitoyl transferase (SPT) [23], the ceramide-generating enzymes SMase [16], [24], [25] and GlcCDase [26], and the degradative enzyme ceramidase [13], it was intriguing to determine whether that enzyme balance might be altered in the skin of AD patients. In our earlier study, we reported that there are no significant differences in the
GCer deacylase activity in AD
In focusing on SM metabolism rather than on reactions mediated by CDase or GCase as an unresolved mechanism underlying the ceramide deficiency of the stratum corneum from AD patients, we found a novel abnormally expressed epidermal enzyme related to SM metabolism, termed SM deacylase [8], [9], [10]. The abnormal expression of SM deacylase in the epidermis of AD patients allowed us to speculate that the action of acid SMase becomes deficient, at least in terms of substrate utility, in that
Overall discussion
It is well established that ceramide levels in the stratum corneum are substantially regulated by the dynamic balance between SMase, GlcCDase and ceramidase, which are localized in lamellar granules and are activated via exocytosis of those granules at the border between the granular and the stratum corneum layers. Therefore, it seems reasonable to assume that the ceramide deficiency in the stratum corneum of AD patients could be mainly ascribed to abnormalities in those ceramide-related
References (38)
- et al.
Ganglioside-mediated modulation of cell growth
J Biol Chem
(1986) - et al.
Characterization of a ceramide kinase activity from human leukemia (HL-60) cells
J Biol Chem
(1990) - et al.
Decreased level of ceramides in stratum corneum of atopic dermatitis: An etiologic factor in atopic dry skin?
J Invest Dermatol
(1991) - et al.
High-expression of sphingomyelin deacylase is an important determinant of ceramide deficiency leading to barrier disruption in atopic dermatitis
J Invest Dermatol
(2000) - et al.
Abnormal expression of sphingomyelin acylase in atopic dermatitis: an etiologic factor for ceramide deficiency?
J Invest Dermatol
(1996) - et al.
A novel enzyme that cleaves the N-acyl linkage of ceramides in various glycosphingolipids as well as sphingomyelin to produce their lyso form
J Biol Chem
(1995) - et al.
Purification and biochemical characterization of membrane-bound epidermal ceramidases from guinea pig skin
J Biol Chem
(1995) - et al.
Ceramidase activity in porcine epidermis
FEBS Lett
(1990) - et al.
Cloning and characterization of the full-length cDNA and genomic sequences encoding murine acid ceramidase
Genomics
(1998) - et al.
Sphingomyelinase in pig and human epidermis
J Invest Dermatol
(1978)