Cooperative Synthesis of Ultra Long-Chain Fatty Acid and Ceramide during Keratinocyte Differentiation.

PLoS One 2013 27;8(6):e67317. Epub 2013 Jun 27.

Laboratory of Biomembrane and Biofunctional Chemistry, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan.

The lipid lamellae in the stratum corneum is important for the epidermal permeability barrier. The lipid lamellae component ceramide (CER), comprising an ultra long-chain (ULC) fatty acid (FA) of ≥26 carbons (ULC CER), plays an essential role in barrier formation. ULC acyl-CoAs, produced by the FA elongase ELOVL4, are converted to ULC CERs by the CER synthase CERS3. In the presented study, we observed that ELOVL4 and CERS3 mRNAs increased during keratinocyte differentiation in vivo and in vitro. We also determined that peroxisome proliferator-activated receptor β/δ is involved in the up-regulation of the mRNAs. Knockdown of CERS3 caused a reduction in the elongase activities toward ULC acyl-CoAs, suggesting that CERS3 positively regulates ULCFA. Thus, we reveal that the two key players in ULC CER production in epidermis, CERS3 and ELOVL4, are coordinately regulated at both the transcriptional and enzymatic levels.

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0067317PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3694974PMC
October 2017
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(Supplied by CrossRef)
The skin: an indispensable barrier
E Proksch et al.
Exp Dermatol 2008
Mammalian ceramide synthases
M Levy et al.
IUBMB Life 2010
The ω-hydroxyceramides of pig epidermis are attached to corneocytes solely through omega-hydroxyl groups
ME Stewart et al.
J Lipid Res 2001

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