Involvement of caspase-3 and GD3 ganglioside in ceramide-induced apoptosis in Farber disease
Involvement of caspase-3 and GD3 ganglioside in ceramide-induced apoptosis in Farber disease
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DOI：
10.1177/002215540004800106
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发表时间：
2000-01-01
影响因子：
3.2
通讯作者：
Stassi, G
中科院分区：
文献类型：
--
作者：
Farina, F;Cappello, F;Stassi, G
法伯病（FD）是一种罕见的遗传性疾病，由神经酰胺酶缺乏引起，导致神经酰胺在肺、肝、结肠、骨骼肌、软骨和骨中积聚。虽然该病已被病理学特征，很少有人知道它的分子发病过程。由于最近的研究报道，神经酰胺的积累诱导GD 3神经节苷脂的形成和细胞凋亡，我们调查，通过结肠镜检查获得的组织从严重参与的患者，神经酰胺在FD结肠细胞破坏的可能参与。石蜡包埋切片的组织化学和TUNEL分析显示，与8 +/- 2.3%的组成性上皮细胞死亡相比，45 +/- 4.3%的FD结肠细胞显示出凋亡的形态学迹象。重要的是，促凋亡因子的免疫组织化学研究表明，GD 3积累与活性caspase-3和裂解的K18在FD结肠组织中共定位。这些发现为神经酰胺途径凋亡在FD发病机制中的作用提供了证据。
Farber's disease (FD) is a rare genetic disorder caused by ceramidase deficiency, which results in ceramide accumulation in lung, liver, colon, skeletal muscle, cartilage, and bone. Although this disease has been symptomatically characterized, little is known about its molecular pathogenetic process. Because recent studies reported that ceramide accumulation induces GD3 ganglioside formation and apoptosis, we investigated, in tissue obtained via colonoscopy from seriously involved patients, the possible involvement of ceramide in FD colonocyte destruction. Histochemical and TUNEL analyses of paraffin-embedded sections revealed that 45 +/- 4.3% of FD colonocytes showed morphological signs of apoptosis compared with the 8 +/- 2.3% of constitutive epithelial cell death. Importantly, immunohistochemical study for pro-apoptotic factors showed that GD3 accumulation colocalized with active caspase-3 and cleaved K18 in FD colon tissue. These findings provide evidence for a role of the apoptotic ceramide pathway in the pathogenesis of FD.