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New insights on the use of desipramine as an inhibitor for acid ceramidase
Author(s) -
Elojeimy Saeed,
Holman David H.,
Liu Xiang,
El-Zawahry Ahmed,
Villani Maristella,
Cheng Joseph C.,
Mahdy Ayman,
Zeidan Youssef,
Bielwaska Alicja,
Hannun Yusuf A.,
Norris James S.
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.07.071
Subject(s) - desipramine , chemistry , pharmacology , biochemistry , endocrinology , biology , antidepressant , hippocampus
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.