title: Glucosylceramide synthesis inhibitors block pharmacologically induced dispersal of the Golgi and anterograde membrane flow from the endoplasmic reticulum: implication of sphingolipid metabolism in maintenance of the Golgi architecture and anterograde membrane flow.
abstract: PDMP (D,L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol) and PPMP (D,L-threo-1-phenyl-2-hexadecanoylamino-3-morpholino-1-propanol), inhibitors of glucosylceramide synthesis, blocked brefeldin A (BFA)- and nordihydroguaiaretic acid-induced dispersal of the Golgi and trans Golgi network, and Golgi-derived vesicles were retained in the juxtanuclear region. PDMP and PPMP did not stabilize microtubules but blocked nocodazole-induced extensive fragmentation and dispersal of the Golgi, and large Golgi vesicles were retained in the juxtanuclear region. PPMP is a stronger inhibitor of glucosylceramide synthesis than PDMP, but PDMP showed a stronger activity against BFA-induced retrograde membrane flow. However, PPMP showed a stronger activity for Golgi disruption and inhibition of anterograde trafficking from the endoplasmic reticulum, and rebuilding of the Golgi architecture. Cumulatively, these results suggest that sphingolipid metabolism is implicated in maintenance of the Golgi architecture and anterograde membrane flow from the endoplasmic reticulum but not in Golgi dispersal induced by BFA.
authors.affiliation: Animal and Cellular Systems Laboratory, RIKEN The Institute of Physical and Chemical Research, Saitama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: N
authors.initials: N
authors.lastname: Kuroiwa
authors.forename: Y
authors.initials: Y
authors.lastname: Kono
authors.forename: A
authors.initials: A
authors.lastname: Takatsuki
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D020126:Brefeldin A / Q000037:antagonists & inhibitors; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005456:Fluorescent Dyes; D005963:Glucosylceramides / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D006056:Golgi Apparatus / Q000187:drug effects* / Q000648:ultrastructure; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure; D009025:Morpholines / Q000494:pharmacology*; D015739:Nocodazole / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D013107:Sphingolipids / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: C095823:1-phenyl-2-palmitoylamino-3-morpholino-1-propanol; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D005963:Glucosylceramides; D016859:Lipoxygenase Inhibitors; D009025:Morpholines; D013107:Sphingolipids; D020126:Brefeldin A; C033110:RV 538; D009637:Masoprocol; D000255:Adenosine Triphosphate; D015739:Nocodazole