PMID- 11589008 OWN - NLM STAT- MEDLINE DCOM- 20011101 LR - 20220321 IS - 1090-3798 (Print) IS - 1090-3798 (Linking) VI - 5 Suppl A DP - 2001 TI - Role of palmitoyl-protein thioesterase in cell death: implications for infantile neuronal ceroid lipofuscinosis. PG - 53-5 AB - Infantile neuronal ceroid lipofuscinosis (INCL) is a childhood neurodegenerative disease caused by the selective death of cortical and retinal neurons as the result of an inherited palmitoyl-protein thioesterase 1 (PPT1) deficiency. Neuronal death is common to many lysosomal storage diseases but it occurs very early in INCL and we show here that inhibition of PPT1 increases the susceptibility of these cells to apoptotic cell death. Thus transient transfection of LA-N-5 neuroblastoma cells with a reverse-oriented (antisense) PPT1 (AS-PPT1) reduced PPT1 enzyme activity (as measured by an in vitro assay) and increased the susceptibility to apoptosis induced by C2 ceramide. Similarly, inhibition of PPT1 with a synthetic inhibitor (AcG-palmitoyl diaminoproprionate-VKIKK) (DAP1) (100 microM) increased the susceptibility of the cells to apoptosis induced by either C2-ceramide or etoposide and Adriamycin (doxorubicin), common chemotherapeutic agents used in the treatment of solid tumours. In contrast, overexpression of PPT1 led to increased resistance to cell death induced by these drugs. FAU - Cho, S AU - Cho S AD - Departments of Pediatrics, Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA. FAU - Dawson, P E AU - Dawson PE FAU - Dawson, G AU - Dawson G LA - eng GR - HD-09402/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Eur J Paediatr Neurol JT - European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society JID - 9715169 RN - 0 (Antibiotics, Antineoplastic) RN - 0 (Chromones) RN - 0 (Enzyme Inhibitors) RN - 0 (Morpholines) RN - 0 (N-acetylsphingosine) RN - 0 (Nucleic Acid Synthesis Inhibitors) RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) RN - 6PLQ3CP4P3 (Etoposide) RN - EC 3.1.2.- (Thiolester Hydrolases) RN - EC 3.1.2.22 (palmitoyl-protein thioesterase) RN - H88EPA0A3N (Staurosporine) RN - NGZ37HRE42 (Sphingosine) RN - ZS7284E0ZP (Daunorubicin) SB - IM MH - Antibiotics, Antineoplastic/pharmacology MH - Apoptosis/drug effects/*physiology MH - Chromones/pharmacology MH - Daunorubicin/pharmacology MH - Enzyme Inhibitors/pharmacology MH - Etoposide/pharmacology MH - Humans MH - Infant MH - Morpholines/pharmacology MH - Nerve Degeneration/enzymology MH - Neuroblastoma MH - Neuronal Ceroid-Lipofuscinoses/*enzymology MH - Neurons/cytology/enzymology MH - Nucleic Acid Synthesis Inhibitors/pharmacology MH - Sphingosine/analogs & derivatives/pharmacology MH - Staurosporine/pharmacology MH - Thiolester Hydrolases/genetics/*metabolism MH - Transfection MH - Tumor Cells, Cultured EDAT- 2001/10/09 10:00 MHDA- 2001/11/03 10:01 CRDT- 2001/10/09 10:00 PHST- 2001/10/09 10:00 [pubmed] PHST- 2001/11/03 10:01 [medline] PHST- 2001/10/09 10:00 [entrez] AID - S10903798(00)90409-4 [pii] AID - 10.1053/ejpn.2000.0435 [doi] PST - ppublish SO - Eur J Paediatr Neurol. 2001;5 Suppl A:53-5. doi: 10.1053/ejpn.2000.0435.