Living Skin Bank, Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794-8702, USA.
Mol Cell Biochem. 2012 May;364(1-2):351-61. doi: 10.1007/s11010-012-1237-7. Epub 2012 Feb 4.
Retinol and its metabolites modulate epithelial differentiation and serve as cellular UV sensors through changes in retinoid status. Of note is the dehydroretinol family which may serve functions distinct from parental retinol. This study focuses on the metabolism of this family and its potential participation in the response of normal epidermal human keratinocytes to UV irradiation. There were three findings. First, keratinocytes contain two pools of dehydroretinyl esters, one of which is shielded from UVB-, but not from UVA-induced decomposition. Second, using a novel in vitro assay we demonstrated that both UVA and UVB promote dehydroretinol biosynthesis in keratinocytes, but only UVB exposure promotes retinoid ester accretion by enhancing the activity of at least one acyl transferase. Finally, dehydroretinol sufficiency reduces UVA/B driven apoptosis more effectively than retinol sufficiency. This may in part be due to differences in the expression of Fas ligand, which we found to be upregulated by retinoic acid, but not dehydroretinoic acid. These observations implicate a role of dehydroretinol and its metabolites in UVA/B adaptation. Thus, the keratinocyte response to UV is jointly shaped by both the retinoids and dehydroretinoids.
视黄醇及其代谢物通过改变视黄醇状态来调节上皮细胞分化，并作为细胞紫外线传感器。值得注意的是脱氢视黄醇家族，它可能具有与母体视黄醇不同的功能。本研究专注于该家族的代谢及其在正常表皮人角质形成细胞对紫外线照射反应中的潜在参与。有三个发现。首先，角质形成细胞包含两个脱氢视黄醇酯池，其中一个池受到 UVB 的屏蔽，但不受 UVA 诱导的分解的影响。其次，使用一种新的体外测定法，我们证明 UVA 和 UVB 均可促进角质形成细胞中脱氢视黄醇的生物合成，但只有 UVB 暴露通过增强至少一种酰基转移酶的活性来促进类视黄醇酯的积累。最后，脱氢视黄醇的充足可更有效地减少 UVA/B 驱动的细胞凋亡，而视黄醇的充足则不然。这可能部分是由于 Fas 配体的表达差异所致，我们发现 Fas 配体受视黄酸上调，但不受脱氢视黄酸上调。这些观察结果表明脱氢视黄醇及其代谢物在 UVA/B 适应中起作用。因此，角质形成细胞对 UV 的反应是由视黄醇和脱氢视黄醇共同塑造的。
