Comprehensive stratum corneum ceramide profiling reveals reduced acylceramides in ichthyosis patient with CERS3 mutations
| العنوان: | Comprehensive stratum corneum ceramide profiling reveals reduced acylceramides in ichthyosis patient with CERS3 mutations |
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| المؤلفون: | Yasutomo Imai, Kiyofumi Yamanishi, Hiroyasu Uemura, Takayuki Sassa, Masaaki Kugo, Akio Kihara, Hideki Hayashi, Yuki Kyono, Moe Yamamoto |
| المصدر: | The Journal of Dermatology. 48:447-456 |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | medicine.medical_specialty, Ceramide, Nonsense mutation, acylceramide, Dermatology, Ceramides, 030207 dermatology & venereal diseases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Congenital ichthyosis, medicine, Stratum corneum, Humans, stratum corneum, ceramide, biology, Sphingosine, Ichthyosis, Ceramide synthase 3, General Medicine, medicine.disease, Sphingolipid, medicine.anatomical_structure, Endocrinology, chemistry, 030220 oncology & carcinogenesis, Mutation, biology.protein, ichthyosis, sphingolipid, Epidermis, Ichthyosis, Lamellar |
| الوصف: | The stratum corneum (SC) of the epidermis acts as a skin permeability barrier, and abnormalities in SC formation lead to several skin disorders. Lipids, especially the epidermis-specific ceramide classes omega-O-acylceramides (acylceramides) and protein-bound ceramides, are essential for skin barrier formation. Ceramide synthase 3 (CERS3) is involved in the synthesis of acylceramides and protein-bound ceramides, and CERS3 mutations cause autosomal recessive congenital ichthyosis. In the present study, we measured ceramide synthase activity and performed comprehensive SC ceramide profiling in an ichthyosis patient with compound heterozygous CERS3 mutations: nonsense mutation p.Arg75* and missense mutation p.Arg229His. The activity of p.Arg75* and p.Arg229His mutant CERS3 proteins was reduced to 4% and 56%, respectively, of the wild-type protein. In the patient's SC, acylceramide levels were greatly reduced, but the levels of protein-bound ceramides remained almost unchanged. Non-acylated ceramide levels were also affected in the patient; in particular, the levels of ceramides composed of sphingosine and non-hydroxy or alpha-hydroxy fatty acid were substantially higher than in healthy controls. These results suggest that a reduction in acylceramide levels alone leads to ichthyosis. Although protein-bound ceramides are synthesized from acylceramides, levels of acylceramides and protein-bound ceramides are not necessarily correlated. |
| وصف الملف: | application/pdf |
| تدمد: | 1346-8138 0385-2407 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e9680dbd0cf45823bf4156f0374f298d https://doi.org/10.1111/1346-8138.15725 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e9680dbd0cf45823bf4156f0374f298d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13468138 03852407 |
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