title: Cooperative Synthesis of Ultra Long-Chain Fatty Acid and Ceramide during Keratinocyte Differentiation.
abstract: 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.
authors.affiliation: Laboratory of Biomembrane and Biofunctional Chemistry, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Mizutani
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ohno
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sassa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Wakashima
authors.forename: Mari
authors.initials: M
authors.lastname: Obara
authors.forename: Kohei
authors.initials: K
authors.lastname: Yuyama
authors.forename: Akio
authors.initials: A
authors.lastname: Kihara
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Igarashi
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D002518:Ceramides / Q000096:biosynthesis*; D005136:Eye Proteins / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D017403:In Situ Hybridization; D015603:Keratinocytes / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism; D048068:PPAR-beta / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D051049:Sphingosine N-Acyltransferase / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D002518:Ceramides; C418975:ELOVL4 protein, human; D005136:Eye Proteins; D005227:Fatty Acids; D008565:Membrane Proteins; D047494:PPAR delta; D048068:PPAR-beta; D012333:RNA, Messenger; C583317:CERS3 protein, human; D051049:Sphingosine N-Acyltransferase