Cooperative Synthesis of Ultra Long-Chain Fatty Acid and Ceramide during Keratinocyte Differentiation.
Cooperative Synthesis of Ultra Long-Chain Fatty Acid and Ceramide during Keratinocyte Differentiation.
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DOI：
10.1371/journal.pone.0067317
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Igarashi Y
中科院分区：
文献类型：
--
作者：
Mizutani Y;Sun H;Ohno Y;Sassa T;Wakashima T;Obara M;Yuyama K;Kihara A;Igarashi Y
角质层中的脂层对于表皮通透性屏障是重要的。脂膜成分神经酰胺(CER)由≥26碳的超长链脂肪酸(ULC CER)组成，在屏障的形成中起着至关重要的作用。由FA延伸酶ELOVL4产生的ULC酰基-COA被CER合成酶CERS3转化为ULC CER。在目前的研究中，我们观察到在体内和体外角质形成细胞分化过程中ELOVL4和CERS3mRNAs的表达增加。我们还确定了过氧化物酶体增殖物激活受体β/δ参与了mRNA的上调。CERS3基因敲除导致ULC酰基-COAS伸长酶活性降低，提示CERS3对ULCFA具有正向调节作用。因此，我们揭示了在表皮中产生ULC CER的两个关键角色CERS3和ELOVL4在转录和酶水平上都受到协调调控。
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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