Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan.
School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, 02138, USA.
Sci Rep. 2021 Feb 8;11(1):3302. doi: 10.1038/s41598-021-82820-1.
Reduction of elastin in the skin causes various skin diseases as well as wrinkles and sagging with aging. Sialidase is a hydrolase that cleaves a sialic acid residue from sialoglycoconjugate. Cleavage of sialic acid from microfibrils by the sialidase isozyme Neu1 facilitates elastic fiber assembly. In the present study, we showed that a lower layer of the dermis and muscle showed relatively intense sialidase activity. The sialidase activity in the skin decreased with aging. Choline and geranate (CAGE), one of the ionic liquids, can deliver the sialidase subcutaneously while maintaining the enzymatic activity. The elastin level in the dermis was increased by applying sialidase from Arthrobacter ureafaciens (AUSA) with CAGE on the skin for 5 days in rats and senescence-accelerated mice prone 1 and 8. Sialidase activity in the dermis was considered to be mainly due to Neu2 based on the expression level of sialidase isozyme mRNA. Transdermal administration of Neu2 with CAGE also increased the level of elastin in the dermis. Therefore, not only Neu1 but also Neu2 would be involved in elastic fiber assembly. Transdermal administration of sialidase is expected to be useful for improvement of wrinkles and skin disorders due to the loss of elastic fibers.
皮肤中弹性蛋白的减少会导致各种皮肤疾病，以及随着年龄增长出现皱纹和松弛。唾液酸酶是一种水解酶，能够从唾液酸糖缀合物中切割唾液酸残基。唾液酸酶同工酶 Neu1 从微原纤维上切割唾液酸，有助于弹性纤维的组装。在本研究中，我们表明真皮和肌肉的较下层显示出相对较强的唾液酸酶活性。皮肤中的唾液酸酶活性随年龄增长而降低。胆碱和格尔纳特（CAGE）是一种离子液体，可以将唾液酸酶经皮输送，同时保持酶的活性。在大鼠和快速老化品系 1 和 8 小鼠中，将产脲节杆菌来源的唾液酸酶（AUSA）与 CAGE 一起应用于皮肤 5 天，可增加真皮中的弹性蛋白水平。基于唾液酸酶同工酶 mRNA 的表达水平，认为真皮中的唾液酸酶活性主要归因于 Neu2。用 CAGE 经皮给予 Neu2 也增加了真皮中弹性蛋白的水平。因此，不仅 Neu1，而且 Neu2 也可能参与弹性纤维的组装。经皮给予唾液酸酶有望用于改善因弹性纤维丧失而引起的皱纹和皮肤疾病。
