| RRC ID |
22711
|
| 著者 |
Sassa T, Ohno Y, Suzuki S, Nomura T, Nishioka C, Kashiwagi T, Hirayama T, Akiyama M, Taguchi R, Shimizu H, Itohara S, Kihara A.
|
| タイトル |
Impaired epidermal permeability barrier in mice lacking elovl1, the gene responsible for very-long-chain fatty acid production.
|
| ジャーナル |
Mol Cell Biol
|
| Abstract |
The sphingolipid backbone ceramide (Cer) is a major component of lipid lamellae in the stratum corneum of epidermis and has a pivotal role in epidermal barrier formation. Unlike Cers in other tissues, Cers in epidermis contain extremely long fatty acids (FAs). Decreases in epidermal Cer levels, as well as changes in their FA chain lengths, cause several cutaneous disorders. However, the molecular mechanisms that produce such extremely long Cers and determine their chain lengths are poorly understood. We generated mice deficient in the Elovl1 gene, which encodes the FA elongase responsible for producing C20 to C28 FAs. Elovl1 knockout mice died shortly after birth due to epidermal barrier defects. The lipid lamellae in the stratum corneum were largely diminished in these mice. In the epidermis of the Elovl1-null mice, the levels of Cers with ≥C26 FAs were decreased, while those of Cers with ≤C24 FAs were increased. In contrast, the levels of C24 sphingomyelin were reduced, accompanied by an increase in C20 sphingomyelin levels. Two ceramide synthases, CerS2 and CerS3, expressed in an epidermal layer-specific manner, regulate Elovl1 to produce acyl coenzyme As with different chain lengths. Elovl1 is a key determinant of epidermal Cer chain length and is essential for permeability barrier formation.
|
| 巻・号 |
33(14)
|
| ページ |
2787-96
|
| 公開日 |
2013-7-1
|
| DOI |
10.1128/MCB.00192-13
|
| PII |
MCB.00192-13
|
| PMID |
23689133
|
| PMC |
PMC3700134
|
| MeSH |
Acetyltransferases / deficiency
Acetyltransferases / genetics*
Animals
Ceramides / metabolism
Cytoplasmic Granules / metabolism
Epidermis / abnormalities
Epidermis / enzymology*
Epidermis / pathology
Fatty Acid Elongases
Fatty Acids / metabolism*
Female
Genes, Lethal
HEK293 Cells
Humans
Lipid Metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Permeability
Sphingosine N-Acyltransferase / metabolism
|
| IF |
3.611
|
| 引用数 |
69
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| 実験動物マウス |
RBRC01828 |
