Extra-Lysosomal Localization of Arylsulfatase B in Human Colonic Epithelium

Extra-Lysosomal Localization of Arylsulfatase B in Human Colonic Epithelium
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DOI:
10.1369/0022155410395511
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发表时间:
2011-03-01
影响因子:
3.2
通讯作者:
Tobacman, Joanne K.
Tobacman, Joanne K.
中科院分区:
生物学3区
文献类型:
--
作者:
Prabhu, Sanjiv V.;Bhattacharyya, Sumit;Tobacman, Joanne K.

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芳基硫酸酯酶B(N-乙酰半乳糖胺-4-硫酸酯酶; ARSB; AS B)从硫酸化糖胺聚糖(sGAG)、软骨素-4-硫酸酯(C4 S)和硫酸皮肤素(DS)中去除4-硫酸酯基团。先天性ARSB缺乏导致溶酶体贮积病粘多糖沉积症VI,其特征在于重要器官中sGAG的积累、正常生理过程的破坏、严重发病和过早死亡。最近发表的工作表明,在支气管和结肠上皮细胞、脑血管细胞和肝细胞中观察到核和细胞膜ARSB的溶酶体外定位。在这份报告中,作者介绍了结肠微阵列中的ARSB免疫染色,并显示了正常结肠、腺瘤和腺癌中ARSB染色的分布、强度和模式的差异。在正常上皮细胞中存在明显的强烈的管腔膜染色,但在恶性肿瘤中减少,并且在3级中少于1级腺癌。在正常的核心,强烈的细胞质阳性的管腔表面的独特模式,其次是减少染色更深的隐窝。ARSB酶活性在正常组织中显著高于恶性组织。这些研究结果证实了ARSB的溶酶体外定位,并表明ARSB免疫染色改变和活性降低可能是人类结肠组织恶性转化的有用指标。(J Histochem Cytochem 59:328-335,2011)
The enzyme arylsulfatase B (N-acetylgalactosamine-4-sulfatase; ARSB; ASB) removes 4-sulfate groups from the sulfated glycosaminoglycans (sGAG) chondroitin-4-sulfate (C4S) and dermatan sulfate (DS). Inborn deficiency of ARSB leads to the lysosomal storage disease mucopolysaccharidosis VI, characterized by accumulation of sGAG in vital organs, disruption of normal physiological processes, severe morbidity, and premature death. Recent published work demonstrated extra-lysosomal localization with nuclear and cell membrane ARSB observed in bronchial and colonic epithelial cells, cerebrovascular cells, and hepatic cells. In this report, the authors present ARSB immunostaining in a colonic microarray and show differences in distribution, intensity, and pattern of ARSB staining among normal colon, adenomas, and adenocarcinomas. Distinctive, intense luminal membrane staining was present in the normal epithelial cells but reduced in the malignancies and less in the grade 3 than in the grade 1 adenocarcinomas. In the normal cores, a distinctive pattern of intense cytoplasmic positivity at the luminal surface was followed by reduced staining deeper in the crypts. ARSB enzymatic activity was significantly greater in normal than in malignant tissue. These study findings affirm extra-lysosomal localization of ARSB and suggest that altered ARSB immunostaining and reduced activity may be useful indicators of malignant transformation in human colonic tissue. (J Histochem Cytochem 59:328-335, 2011)