Senescence-associated beta-galactosidase is lysosomal beta-galactosidase.
Senescence-associated beta-galactosidase is lysosomal beta-galactosidase.
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DOI：
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发表时间：
2006
期刊：
影响因子：
7.8
通讯作者：
Bo Yun Lee;Jung-A Han;Jun-Sub Im;A. Morrone;K. Johung;E. Goodwin;W. Kleijer;D. DiMaio;E. Hwang
中科院分区：
文献类型：
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作者：
Bo Yun Lee;Jung-A Han;Jun-Sub Im;A. Morrone;K. Johung;E. Goodwin;W. Kleijer;D. DiMaio;E. Hwang
复制性衰老限制了培养物中传代的体细胞的增殖，并且可能反映了体内的细胞衰老。衰老和老化细胞最广泛使用的生物标志物是衰老相关的β-半乳糖苷酶（SA-β-gal），其定义为在衰老细胞中在pH 6.0下可检测到的β-半乳糖苷酶活性，但SA-β-gal的起源及其在衰老中的细胞作用尚不清楚。我们在这里证明SA-β-gal活性是由GLB 1表达的，GLB 1是编码溶酶体β-D-半乳糖苷酶的基因，其活性通常在酸性pH 4.5下测量。来自常染色体隐性遗传G（M1）-神经节苷脂沉积症患者的成纤维细胞，其具有缺陷的溶酶体β-半乳糖苷酶，在后期传代时不表达SA-β-gal，即使它们经历复制性衰老。此外，晚期传代正常成纤维细胞表达小发夹干扰RNA，耗尽GLB 1 mRNA经历衰老，但未能表达SA-β-gal。GLB 1 mRNA耗竭也阻止了HeLa宫颈癌细胞中SA-β-gal活性的表达，该细胞通过内源性人乳头瘤病毒E7癌基因的抑制而诱导进入衰老状态。衰老过程中SA-β-gal诱导至少部分是由于溶酶体β-半乳糖苷酶蛋白表达增加。这些结果还表明，SA-β-gal不是衰老所必需的。
Replicative senescence limits the proliferation of somatic cells passaged in culture and may reflect cellular aging in vivo. The most widely used biomarker for senescent and aging cells is senescence-associated beta-galactosidase (SA-beta-gal), which is defined as beta-galactosidase activity detectable at pH 6.0 in senescent cells, but the origin of SA-beta-gal and its cellular roles in senescence are not known. We demonstrate here that SA-beta-gal activity is expressed from GLB1, the gene encoding lysosomal beta-D-galactosidase, the activity of which is typically measured at acidic pH 4.5. Fibroblasts from patients with autosomal recessive G(M1)-gangliosidosis, which have defective lysosomal beta-galactosidase, did not express SA-beta-gal at late passages even though they underwent replicative senescence. In addition, late passage normal fibroblasts expressing small-hairpin interfering RNA that depleted GLB1 mRNA underwent senescence but failed to express SA-beta-gal. GLB1 mRNA depletion also prevented expression of SA-beta-gal activity in HeLa cervical carcinoma cells induced to enter a senescent state by repression of their endogenous human papillomavirus E7 oncogene. SA-beta-gal induction during senescence was due at least in part to increased expression of the lysosomal beta-galactosidase protein. These results also indicate that SA-beta-gal is not required for senescence.