Shen Yanqin, Kohla Guido, Lrhorfi Aicha L, Sipos Bence, Kalthoff Holger, Gerwig Gerrit J, Kamerling Johannis P, Schauer Roland, Tiralongo Joe
Biochemisches Institut, Christian-Albrechts-Universität zu Kiel, Germany.
Eur J Biochem. 2004 Jan;271(2):281-90. doi: 10.1046/j.1432-1033.2003.03927.x.
A decrease in the level of O-acetylated sialic acids observed in colorectal carcinoma may lead to an increase in the expression of sialyl Lewis(X), a tumor-associated antigen, which is related to progression of colorectal cancer to metastasis. The underlying mechanism for this reduction is, however, not fully understood. Two enzymes are thought to be primarily responsible for the turnover of O-acetyl ester groups on sialic acids; sialate-O-acetyltransferase (OAT) and sialate-O-acetylesterase (OAE). We have previously reported the characterization of OAT activity from normal colon mucosa, which efficiently O-acetylates CMP-Neu5Ac exclusively in the Golgi apparatus prior to the action of sialyltransferase. In this report we describe the identification of a lysosomal and a cytosolic OAE activity in human colonic mucosa that specifically hydrolyses 9-O-acetyl groups on sialic acid. Utilizing matched resection margin and cancer tissue from colorectal carcinoma patients we provide strong evidence suggesting that the level of O-acetylated sialic acids present in normal and diseased human colon may be dependent on the relative activities of OAT to lysosomal OAE. Furthermore, we show that the level of free cytosolic Neu5,9Ac2 in human colon is regulated by the relative activity of the cytosolic OAE.
在结直肠癌中观察到的O-乙酰化唾液酸水平降低可能导致唾液酸Lewis(X)（一种肿瘤相关抗原）表达增加，这与结直肠癌进展至转移有关。然而，这种降低的潜在机制尚未完全了解。两种酶被认为主要负责唾液酸上O-乙酰酯基团的周转；唾液酸-O-乙酰基转移酶（OAT）和唾液酸-O-乙酰酯酶（OAE）。我们之前报道了正常结肠黏膜中OAT活性的特征，其在唾液酸转移酶作用之前仅在高尔基体中有效地将CMP-Neu5Ac进行O-乙酰化。在本报告中，我们描述了在人结肠黏膜中鉴定出一种溶酶体和一种胞质OAE活性，其特异性水解唾液酸上的9-O-乙酰基。利用来自结直肠癌患者的配对切缘和癌组织，我们提供了有力证据表明正常和患病的人结肠中存在的O-乙酰化唾液酸水平可能取决于OAT与溶酶体OAE的相对活性。此外，我们表明人结肠中游离胞质Neu5,9Ac2的水平受胞质OAE相对活性的调节。
