Novel blockade by brefeldin A of intracellular transport of secretory proteins in cultured rat hepatocytes.

Misumi, Yoshio; Miki, Kazumasa; Takatsuki, Akira; Tamura, Gakuzo; Ikehara, Yukio

doi:10.1016/s0021-9258(18)67398-3

Cited by 809 publications

(124 citation statements)

References 40 publications

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“…Wild type (WT) RAW264 cells were stimulated with LPS in the presence or absence of Brefeldin A for 8 h. Brefeldin A inhibits protein transport from the endoplasmic reticulum to the Golgi apparatus [ 33 ]. mTNF was detected as two bands by western blotting ( Fig.…”

Section: Resultsmentioning

confidence: 99%

A potent endocytosis inhibitor Ikarugamycin up-regulates TNF production

Minamidate

Onizawa

Saito

et al. 2021

Biochemistry and Biophysics Reports

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Ikarugamycin (IK) is an antibiotic which has been reported to have a variety of functions, such as inhibition of clathrin-mediated endocytosis (CME), anti-tumor effects and regulation of the immune system. Whether IK influences cytokine production is poorly understood. We have investigated the relationship between IK and production of tumor necrosis factor-α (TNF). TNF plays a pivotal role in pathogenesis of many diseases. Although the dynamics of soluble TNF (sTNF) has been widely explored so far, the functions of the membrane form of TNF (mTNF) have not been fully elucidated. We demonstrated that IK increases the amount of mTNF and prolongs the duration of TNF expression. This effect is unrelated to the shedding activity of disintegrin and metalloproteinase domain-containing protein 17 (ADAM 17). Our results revealed that there is a mechanism to terminate inflammation at the cellular level which IK dysregulates. Furthermore, IK can be a tool to study TNF signaling due to its effect of increasing mTNF expression.

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Section: Resultsmentioning

confidence: 99%

A potent endocytosis inhibitor Ikarugamycin up-regulates TNF production

Minamidate

Onizawa

Saito

et al. 2021

Biochemistry and Biophysics Reports

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“…While Fbxo45 lacks an N-terminal endoplasmic reticulum (ER) translocation signal for conventional secretion (43), some proteins that lack signal peptides are secreted by unconventional pathways (44)(45)(46)(47). To test whether Fbxo45 is secreted by an unconventional pathway, we used brefeldin A (BFA), which inhibits conventional but not unconventional secretion (48). BFA slightly increased the secretion of T7-Fbxo45 but inhibited the secretion of a similar-sized N-terminal signal sequence protein, EC1-T7 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Fbxo45 Binds SPRY Motifs in the Extracellular Domain of N-Cadherin and Regulates Neuron Migration during Brain Development

Calvo-Jiménez

Kon

et al. 2020

Molecular and Cellular Biology

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Several events during the normal development of the mammalian neocortex depend on N-cadherin, including the radial migration of immature projection neurons into the cortical plate. Remarkably, radial migration requires the N-cadherin extracellular domain but not N-cadherin-dependent homophilic cell-cell adhesion, suggesting that other N-cadherin-binding proteins may be involved. We used proximity ligation and affinity purification proteomics to identify N-cadherin-binding proteins. Both screens detected MycBP2 and SPRY domain protein Fbxo45, two components of an intracellular E3 ubiquitin ligase. Fbxo45 appears to be secreted by a nonclassical mechanism, not involving a signal peptide and not requiring transport from the endoplasmic reticulum to the Golgi apparatus. Fbxo45 binding requires N-cadherin SPRY motifs that are not involved in cell-cell adhesion. SPRY mutant N-cadherin does not support radial migration in vivo. Radial migration was similarly inhibited when Fbxo45 expression was suppressed. The results suggest that projection neuron migration requires both Fbxo45 and the binding of Fbxo45 or another protein to SPRY motifs in the extracellular domain of N-cadherin.

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“…To assess the involvement of the vesicular transport pathway in FAEE exiting from cells, we performed experiments in which the HepG2 cells were incubated with inhibitors that interfere with the vesicular transport pathway. Brefeldin A (BFA), a lipophilic fungal metabolite, interferes with protein secretion at the level of cis-Golgi by the disassembly of the Golgi complex and redistribution of Golgi components to the endoplasmic reticulum (31)(32)(33). Monensin is a carboxylic ionophore that inhibits protein secretion at the level of trans-Golgi (34).…”

Section: Resultsmentioning

confidence: 99%

Fatty acid ethyl esters and HepG2 cells: intracellular synthesis and release from the cells

Kabakibi

Morse

Laposata

1998

Journal of Lipid Research

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Fatty acid ethyl esters (FAEE), esterification products of fatty acid and ethanol, have been implicated as mediators of ethanol-induced organ damage. To understand the molecular and cellular events in FAEE synthesis and secretion, we developed a system in which HepG2 cells synthesize and release FAEE into the culture medium upon incubation with ethanol. The synthesis of FAEE was observed within 5 min of the addition of ethanol, with a plateau for FAEE synthesis after 2 h of incubation. It was also observed that FAEE are synthesized by both a microsomal FAEE synthase, which preferentially uses fatty acyl-CoA as a substrate, and a cytosolic FAEE synthase, which accepts both unesterified fatty acid and fatty acyl-CoA as substrates with a slight preference for fatty acyl-CoA. Although the kinetics of cellular FAEE synthesis await further characterization, the intracellular fatty acid substrate appears to be derived principally from glycerolipids and other esters. FAEE were released into the culture medium by a mechanism independent of the vesicular transport pathway. Lipoprotein particles and albumin were found to be carriers of FAEE after FAEE secretion from the cell.-Kabakibi, A., C. R. Morse, and M. Laposata. Fatty acid ethyl esters and HepG2 cells: intracellular synthesis and release from the cells.

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Novel blockade by brefeldin A of intracellular transport of secretory proteins in cultured rat hepatocytes.

Cited by 809 publications

References 40 publications

A potent endocytosis inhibitor Ikarugamycin up-regulates TNF production

A potent endocytosis inhibitor Ikarugamycin up-regulates TNF production

Fbxo45 Binds SPRY Motifs in the Extracellular Domain of N-Cadherin and Regulates Neuron Migration during Brain Development

Fatty acid ethyl esters and HepG2 cells: intracellular synthesis and release from the cells

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