THE TRICYCLIC ANTIDEPRESSANT DESIPRAMINE CAUSES PROTEOLYTIC DEGRADATION OF LYSOSOMAL SPHINGOMYELINASE IN HUMAN FIBROBLASTS
THE TRICYCLIC ANTIDEPRESSANT DESIPRAMINE CAUSES PROTEOLYTIC DEGRADATION OF LYSOSOMAL SPHINGOMYELINASE IN HUMAN FIBROBLASTS
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DOI：
10.1515/bchm3.1994.375.7.447
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发表时间：
1994-07-01
期刊：
影响因子：
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通讯作者：
SANDHOFF, K
中科院分区：
文献类型：
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作者：
HURWITZ, R;FERLINZ, K;SANDHOFF, K
用[S-35]蛋氨酸标记的培养人皮肤成纤维细胞，通过脉冲追踪研究三环抗抑郁药地帕拉明对溶酶体鞘磷脂酶（EC 3.1.4.12）加工的影响。当将地西帕明添加到微摩尔范围的细胞中时，会诱导成熟的酸性鞘磷脂酶在细胞内快速降解，同时使酶活性丧失。脉冲追踪标记显示，25 μ M地西帕明处理成纤维细胞后，成熟酶形态消失。在去地帕明中毒24小时前，用25 μ M胰肽（一种硫醇蛋白酶抑制剂）孵育细胞，可防止这种药物诱导的效应。从这些结果我们得出结论，地西帕明和可能同样作用的三环抗抑郁药诱导酸性鞘磷脂酶的蛋白水解降解。
The effect of the tricyclic antidepressant desipramine on the processing of lysosomal sphingomyelinase (EC 3.1.4.12) was investigated by pulse-chase studies an [S-35]methionine labeled cultured human skin fibroblasts. Desipramine induced rapid intracellular degradation of mature acid sphingomyelinase when added to the cells in the micromolar range, concomitantly abolishing the enzyme activity. Pulse chase labeling revealed the disappearance of mature enzyme forms when fibroblasts were treated with 25 mu M desipramine. Incubation of cells with 25 mu M leupeptin, an inhibitor of thiol proteases, 24h prior to desipramine intoxication prevented this drug-induced effect. From these results we conclude that desipramine and possibly also similarly acting tricyclic antidepressants induce proteolytic degradation of acid sphingomyelinase.