Mepanipyrim, a Novel Inhibitor of Pharmacologically Induced Golgi Dispersion

Abstract

Mepanipyrim inhibited retrograde Golgi-to-ER trafficking induced by brefeldin A (BFA), nordihydroguaiaretic acid, clofibrate, and arachidonyltrifluoromethyl ketone in NRK and other types of cells, but did not inhibit anterograde trafficking of Golgi-resident proteins translocated to ER by BFA and newly synthesized VSV-G. However, mepanipyrim did not block the TGN38 dispersion induced by any of these compounds. Mepanipyrim acted on the Golgi, and swollen vesicular Golgi structures were formed and similar structures accumulated during rebuilding of the Golgi after BFA removal. These actions of mepanipyrim were readily reversed after its removal. Mepanipyrim did not stabilize microtubules, but prevented nocodazole-induced fragmentation and dispersion of the Golgi. These results suggest that the mepanipyrim-sensitive molecules participated in stabilizing the Golgi and its anchoring in the perinuclear region, and equally importantly, that the novel action of mepanipyrim may be used as a pharmacological tool for investigating membrane transport, Golgi membrane dynamics, and differentiation of the Golgi from TGN.

Regio‐ and Chemoselective Metalation of Arenes and Heteroarenes Using Hindered Metal Amide Bases

“…Sonogashira cross-coupling of 205 with propyne furnishes the alkynyl derivative 206 in 97 % yield. Finally, amination of 206 with aniline under Buchwald-Hartwig amination conditions [170][171][172][173] produces the fungicide mepanipyrim 207 [174,175] in 81 % yield (Scheme 38). [169] The metalation of the uracil scaffold can be achieved by selective deprotonation of 2,4-dimethoxypyrimidine.…”

Nonactin hinders intracellular glycosylation in virus-infected baby hamster kidney cells

“…The Golgi complex is fragmented by monensin, but remains localized in the perinuclear region (26). in BFa-treated cells, Golgi components are redistributed to the endoplasmic reticulum or intermediate compartments (21). Golgi staining in nonactin-treated cells was similar to that in control cells, indicating that cytoplasmically dispersed punctate immunofluorescence stains in nonactin-treated cells are caused by fragmentation of the Golgi apparatus.…”

“…Significant efforts have been made to determine the mechanism(s) underlying glycosylation trafficking in cells, particularly with the aid of inhibitors of trafficking, which are powerful tools in these studies (21). However, limited compounds that affect intracellular trafficking processes have been identified to date.…”

Hypoxia activates SREBP2 through Golgi disassembly in bone marrow‐derived monocytes for enhanced tumor growth

“…To investigate whether Golgi disassembly and Golgi-ER fusion are required for SREBP2 activation, we treated monocytic myeloid cells with mepanipyrim. Mepanipyrim has been reported to inhibit Golgi disassembly and BFA-induced retrograde Golgi-to-ER trafficking through a mechanism that is not fully understood (Nakamura et al, 2003). We found that mepanipyrim prevented hypoxiainduced Golgi disassembly ( To further support our hypothesis that hypoxia-induced SREBP2 translocation occurs due to Golgi-ER fusion and consequent Golgito-ER retrograde transport, we treated monocytic myeloid cells with nocodazole and Brefeldin A (BFA), which are two commonly used chemicals to induce Golgi disassembly through different mechanisms (Debose-Boyd et al, 1999).…”