期刊
FEBS LETTERS
卷 580, 期 19, 页码 4751-4756出版社
WILEY
DOI: 10.1016/j.febslet.2006.07.071
关键词
desipramine; ceramide; sphingomyelin; acid ceramidase; acid sphingomyelinase; cationic amphiphilic drugs
资金
- NCI NIH HHS [P01 CA97132] Funding Source: Medline
Treatment of different cancer cell lines with desipramine induced a time- and dose-dependent downregulation of acid ceramidase. Desipramine's effect on acid ceramidase appeared specific for amphiphilic agents (desipramine, chlorpromazine, and chloroquine) but not other lysomotropic agents such as ammonium chloride and bafilomycin A1, and was not transcriptionally regulated. The cathepsin B/L inhibitor, CA074ME, but not the cathepsin D inhibitor, pepstatin A, blocked desipramine's effect on acid ceramidase. Desipramine led to a more pronounced downregulation of sphingosine compared to ceramide suggesting acid ceramidase inhibition is important to desipramine's mechanism of action. This study reveals a new mechanism of action for desipramine. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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