Nowroozi N, Kim S, Gupta A, Warita H, Zernik J
School of Dentistry, University of Southern California, Los Angeles 90089-0641, USA.
J Craniofac Genet Dev Biol. 1999 Jan-Mar;19(1):41-7.
We have previously demonstrated high levels of GM1-ganglioside beta-galactosidase (beta-gal) in the salivary glands of Swiss-Webster mice (Nowroozi et al., J Craniofac Genet Dev Biol 18:51, 1998), and suggested that this activity reflects an important role for the lysosome in catabolism of salivary glycoconjugates. Here, we characterized and compared activities of lysosomal glycosidases among the salivary glands, spleen, and muscle of C57BL/6 mice, beta-gal hexosaminidase, and beta-glucuronidase activities are high in all three glands relative to muscle. Enzyme activities in the sublingual gland were substantially higher than in the submandibular and parotid glands. Spleen displays levels of activity that are comparable or higher (for beta-glucuronidase) than those in the salivary glands, whereas muscle displays substantially lower levels of these lysosomal glycosidases. In order to investigate the role of beta-gal in the salivary glands, we further characterized the salivary phenotype of knock-out mice deficient in this enzyme, mimicking human GM1-gangliosidosis. In contrast with the relative levels of beta-gal specific-activity among the salivary glands, only the parotid developed severe, generalized, degenerative histopathological changes in beta-gal-deficient knock-out mice. GM1-like-ganglioside, typically found at high levels only in the nerve tissue, where its exact function is still not clear, was demonstrated in storage vacuoles of the parotid glands of the deficient mice by binding of cholera toxin subunit B. Thus, beta-gal activity observed in the parotid gland most likely reflects its role in GM1-ganglioside catabolism, and this ganglioside, never previously reported in the salivary glands, may have a role in parotid exocrine secretory functions. beta-gal may also serve in secretory glycoprotein catabolism in other salivary glands, but this function may be non-essential for these glands.
我们之前已证明瑞士韦伯斯特小鼠唾液腺中存在高水平的GM1-神经节苷脂β-半乳糖苷酶（β-半乳糖苷酶）（Nowroozi等人，《颅面遗传学与发育生物学杂志》18:51，1998年），并提出这种活性反映了溶酶体在唾液糖缀合物分解代谢中的重要作用。在此，我们对C57BL/6小鼠的唾液腺、脾脏和肌肉中的溶酶体糖苷酶活性进行了表征和比较，相对于肌肉，β-半乳糖苷酶、己糖胺酶和β-葡萄糖醛酸酶在所有这三个腺体中的活性都很高。舌下腺中的酶活性显著高于下颌下腺和腮腺。脾脏的活性水平与唾液腺相当（对于β-葡萄糖醛酸酶而言）或更高，而肌肉中这些溶酶体糖苷酶的水平则显著较低。为了研究β-半乳糖苷酶在唾液腺中的作用，我们进一步表征了缺乏该酶的基因敲除小鼠的唾液表型，模拟人类GM1-神经节苷脂贮积症。与唾液腺中β-半乳糖苷酶比活性的相对水平相反，在β-半乳糖苷酶缺陷的基因敲除小鼠中，只有腮腺出现了严重的、全身性的、退行性组织病理学变化。通过霍乱毒素B亚基的结合，在缺陷小鼠腮腺的储存泡中证实了GM1样神经节苷脂的存在，这种物质通常仅在神经组织中高水平存在，其确切功能仍不清楚。因此，在腮腺中观察到的β-半乳糖苷酶活性很可能反映了其在GM1-神经节苷脂分解代谢中的作用，并且这种以前从未在唾液腺中报道过的神经节苷脂可能在腮腺外分泌功能中发挥作用。β-半乳糖苷酶也可能参与其他唾液腺中分泌性糖蛋白的分解代谢，但这种功能对这些腺体可能并非必不可少。
