Differentiation-associated expression of ceramidase isoforms in cultured keratinocytes and epidermis
Differentiation-associated expression of ceramidase isoforms in cultured keratinocytes and epidermis
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DOI：
10.1194/jlr.m600001-jlr200
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发表时间：
2006-05-01
影响因子：
6.5
通讯作者：
Uchida, Yoshikazu
中科院分区：
文献类型：
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作者：
Houben, Evi;Holleran, Walter M.;Uchida, Yoshikazu
神经酰胺（Cers）在最外层表皮层或角质层（SC）的间隙内积聚，它们代表表皮渗透屏障的关键组分。虽然SC含有大量的鞘氨醇，表明神经酰胺酶（CD酶）的活性，其中CD酶亚型在表皮中表达仍然没有解决。我们在这里假设，CD酶亚型表达在特定的表皮隔室的功能，本地化到这些层。角质形成细胞/表皮表达所有五种已知的CD酶亚型，其中酸性和碱性CD酶活性随着分化而显著增加，持续进入SC。相反，中性和植物碱性CD酶活性在增殖的角质形成细胞中占主导地位。亚型活性/蛋白质的这些分化相关变化归因于mRNA水平的相应分化相关变化（通过定量RT-PCR）。尽管已知的5种CD酶亚型中有4种广泛表达于皮肤和皮外组织，但碱性CD酶-1几乎仅发生于表皮。这些结果表明，所有五种CD酶亚型的表达和活性存在较大的分化相关性和组织特异性变化。由于碱性CD酶-1和酸性CD酶在分化的表皮区室中选择性上调，它们可以调节定位于远端表皮的功能，例如渗透性屏障稳态和抗微生物防御。
Ceramides (Cers) accumulate within the interstices of the outermost epidermal layers, or stratum corneum (SC), where they represent critical components of the epidermal permeability barrier. Although the SC contains substantial sphingol, indicative of ceramidase (CDase) activity, which CDase isoforms are expressed in epidermis remains unresolved. We hypothesized here that CDase isoforms are expressed within specific epidermal compartments in relation to functions that localize to these layers. Keratinocytes/epidermis express all five known CDase isoforms, of which acidic and alkaline CDase activities increase significantly with differentiation, persisting into the SC. Conversely, neutral and phytoalkaline CDase activities predominate in proliferating keratinocytes. These differentiation-associated changes in isoform activity/protein are attributed to corresponding, differentiation-associated changes in mRNA levels (by quantitative RT-PCR). Although four of the five known CDase isoforms are widely expressed in cutaneous and extracutaneous tissues, alkaline CDase-1 occurs almost exclusively in epidermis. These results demonstrate large, differentiation-associated, and tissue-specific variations in the expression and activities of all five CDase isoforms. Because alkaline CDase-1 and acidic CDase are selectively upregulated in the differentiated epidermal compartment, they could regulate functions that localize to the distal epidermis, such as permeability barrier homeostasis and antimicrobial defense.