Cytoskeletal effects of acrylamide and 2,5-hexanedione: Selective aggregation of vimentin filaments

Sager, Polly R.

doi:10.1016/0041-008x(89)90063-x

Cited by 59 publications

(30 citation statements)

References 37 publications

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“…It is likely that a reduction in microtubules might hinder the intracellular transport of the receptor, leading to an accumulation of the receptor intracellularly. It has been suggested that acrylamide interferes with axonal and intradendritic transport by acting on microtubules as well as MAPs [Lapadula et al, 1989;Sager, 1989;Chauhan et al, 1993]. In our previous study, the colchicine treatment likewise caused an enhanced intracellular level of GABA A R in the neurons [Ho et al, 2001].…”

Section: Discussionmentioning

confidence: 84%

Acrylamide disturbs the subcellular distribution of GABA_A receptor in brain neurons

Wang

Yin

2002

J of Cellular Biochemistry

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Mechanisms underlying the action of acrylamide on neurons were studied by monitoring the expression of GABA(A) receptor (R) in cultured brain neurons derived from chicken embryos. In situ trypsinization of the neurons and 3H-flunitrazepam binding assay were employed to examine the subcellular distribution of GABA(A)R. A 3-h exposure of the cultured neurons to 10 mM of acrylamide raised reversibly the proportion of intracellular (trypsin-resistant) 3H-flunitrazepam binding sites by about 48% and decreased cell surface binding 24% from respective control values, without altering total cellular binding and the affinity of the ligand. Moreover, the acrylamide treatment induced more intense perikaryal immunostaining of GABA(A)R alpha subunit proteins than that in control neurons but did not change the total level of cellular alpha immunostain, in accordance with the binding data. In the cell bodies of acrylamide-treated neurons, the level of neurofilament-200 kDa proteins was similar to control, whereas the tubulin protein content was significantly lowered approximately 51% from control, as revealed by quantifying the immunostained cytoskeletal elements. In addition, electron microscopic observations found reductions in the numbers of microtubules and neurofilaments in the perikarya of acrylamide-treated neurons. As exhibited by the 3H-leucine and 3H-monosaccharide incorporation experiments, the exposure to acrylamide inhibited the rate of general protein synthesis in the culture by 21%, while the rate of glycosylation remained unaltered. Furthermore, in situ hybridization analysis showed that acrylamide did not modify the expression of GABA(A)R alpha subunit mRNAs. Taken together, these data suggest that acrylamide may downregulate the microtubular system and disintegrate neurofilaments, and thereby block the intracellular transport of GABA(A)R, resulting in the accumulation of intracellular receptors.

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Section: Discussionmentioning

confidence: 84%

Acrylamide disturbs the subcellular distribution of GABA_A receptor in brain neurons

Wang

Yin

2002

J of Cellular Biochemistry

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“…The third major component of the cytoskeleton, intermediate filaments, has no established role in melanosome transport [Gyoeva et al, 1987]. However, based on the finding that both microtubules and actin filaments were strongly affected by ACR, and the fact that intermediate filaments are potential targets of ACR [Eckert, 1985;Sager and Matheson, 1988;Sager, 1989;Shiver et al, 1992], we looked at the effects of ACR also on vimentin filaments. To our knowledge, vimentin filaments have not previously been visualized in Xenopus melanophores.…”

Section: Discussionmentioning

confidence: 99%

Effects of acrylamide, latrunculin, and nocodazole on intracellular transport and cytoskeletal organization in melanophores

Aspengren

Wielbass

Wallin

2006

Cell Motil. Cytoskeleton

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The effects of acrylamide (ACR), nocodazole, and latrunculin were studied on intracellular transport and cytoskeletal morphology in cultured Xenopus laevis melanophores, cells that are specialized for regulated and bidirectional melanosome transport. We used three different methods; light microscopy, fluorescence microscopy, and spectrophotometry. ACR affected the morphology of both microtubules and actin filaments in addition to inhibiting retrograde transport of melanosomes but leaving dispersion unaffected. Using the microtubule-inhibitor nocodazole and the actin filament-inhibitor latrunculin we found that microtubules and actin filaments are highly dependent on each other, and removing either component dramatically changed the organization of the other. Both ACR and latrunculin induced bundling of microtubules, while nocodazole promoted formation of filaments resembling stress fibers organized from the cell center to the periphery. Removal of actin filaments inhibited dispersion of melanosomes, further concentrated the central pigment mass in aggregated cells, and induced aggregation even in the absence of melatonin. Nocodazole, on the other hand, prevented aggregation and caused melanosomes to cluster and slowly disperse. Dispersion of nocodazole-treated cells was induced upon addition of alpha-melanocyte-stimulating hormone (MSH), showing that dispersion can proceed in the absence of microtubules, but the distribution pattern was altered. It is well established that ACR has neurotoxic effects, and based on the results in the present study we suggest that ACR has several cellular targets of which the minus-end microtubule motor dynein and the melatonin receptor might be involved. When combining morphological observations with qualitative and quantitative measurements of intracellular transport, melanophores provide a valuable model system for toxicological studies.

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“…ACR has been widely used to selectively and reversibly disrupt vimentin IF without altering microtubule structures (2,65,75) and has been employed in studies addressing the role of IF in Junin, bluetongue, and dengue virus replication (7,13,18). Treatment of HF with ACR prior to infection with AD169 or TB40/E resulted in an exposure time-dependent decrease in the percentage of infected cells ( Fig.…”

Section: Discussionmentioning

confidence: 99%

“…To determine whether the integrity of the vimentin cytoskeleton is required to facilitate the onset of viral infection, HF were treated with a 5 mM ACR solution for 2, 4, 6, or 8 h prior to infection with either AD169 or TB40/E. ACR is a neurotoxin that has been extensively used to disrupt the organization of IF in neurons and in other cells types (2,20,21,33,75). ACR treatment of HF induced cell rounding and contraction, accompanied by the aggregation of vimentin IF in elongated bundles extending into the cells' retraction fibers (Fig.…”

Section: Viral Entry Does Not Alter Vimentin If Structurementioning

confidence: 99%

Onset of Human Cytomegalovirus Replication in Fibroblasts Requires the Presence of an Intact Vimentin Cytoskeleton

Miller

Hertel

2009

J Virol

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Like all viruses, herpesviruses extensively interact with the host cytoskeleton during entry. While microtubules and microfilaments appear to facilitate viral capsid transport toward the nucleus, evidence for a role of intermediate filaments in herpesvirus entry is lacking. Here, we examined the function of vimentin intermediate filaments in fibroblasts during the initial phase of infection of two genotypically distinct strains of human cytomegalovirus (CMV), one with narrow (AD169) and one with broad (TB40/E) cell tropism. Chemical disruption of the vimentin network with acrylamide, intermediate filament bundling in cells from a patient with giant axonal neuropathy, and absence of vimentin in fibroblasts from vimentin ؊/؊ mice severely reduced entry of either strain. In vimentin null cells, viral particles remained in the cytoplasm longer than in vimentin ؉/؉ cells. TB40/E infection was consistently slower than that of AD169 and was more negatively affected by the disruption or absence of vimentin. These findings demonstrate that an intact vimentin network is required for CMV infection onset, that intermediate filaments may function during viral entry to facilitate capsid trafficking and/or docking to the nuclear envelope, and that maintenance of a broader cell tropism is associated with a higher degree of dependence on the vimentin cytoskeleton. viduals (8, 58). Virtually all cell types, with the exception of lymphocytes and polymorphonuclear leukocytes, can support CMV replication in vivo (80), and this remarkably broad tropism is at the basis of the numerous clinical manifestations of CMV infection (8, 58). The range of permissive cells in vitro is more limited, with human fibroblasts (HF) and endothelial cells being the most widely used for propagation of clinical isolates. Two extensively studied strains, AD169 and Towne, were generated by serial passage of tissue isolates in HF for the purpose of vaccine development (22,68). During this process, both strains accumulated numerous genomic changes (11) and lost the ability to grow in cell types other than HF. By contrast, propagation in endothelial cells produced strains with more intact genomes and tropism, such as TB40/E, VR1814, TR, and PH (59, 80). Human cytomegalovirus (CMV) is a ubiquitous herpesvirus that can cause serious disease in immunocompromised indiThe viral determinants of endothelial and epithelial cell tropism have recently been mapped to the UL128-UL131A (UL128-131A) genomic locus (32,92,93). Each of the products of the UL128, UL130, and UL131A genes is independently required for tropism and participates in the formation of a complex at the surface of the virion with the viral glycoproteins gH and gL (74, 93), which can also independently associate with gO (45). The gH/gL/UL128-131A complex appears to be required for entry into endothelial cells by endocytosis, followed by low-pH-dependent fusion of the virus envelope with endosomal membranes (73, 74) although some virus strains expressing the UL128-UL131A genes do not require endosome acid...

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Cytoskeletal effects of acrylamide and 2,5-hexanedione: Selective aggregation of vimentin filaments

Cited by 59 publications

References 37 publications

Acrylamide disturbs the subcellular distribution of GABA_A receptor in brain neurons

Acrylamide disturbs the subcellular distribution of GABA_A receptor in brain neurons

Effects of acrylamide, latrunculin, and nocodazole on intracellular transport and cytoskeletal organization in melanophores

Onset of Human Cytomegalovirus Replication in Fibroblasts Requires the Presence of an Intact Vimentin Cytoskeleton

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Cytoskeletal effects of acrylamide and 2,5-hexanedione: Selective aggregation of vimentin filaments

Cited by 59 publications

References 37 publications

Acrylamide disturbs the subcellular distribution of GABAA receptor in brain neurons

Acrylamide disturbs the subcellular distribution of GABAA receptor in brain neurons

Effects of acrylamide, latrunculin, and nocodazole on intracellular transport and cytoskeletal organization in melanophores

Onset of Human Cytomegalovirus Replication in Fibroblasts Requires the Presence of an Intact Vimentin Cytoskeleton

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Acrylamide disturbs the subcellular distribution of GABA_A receptor in brain neurons

Acrylamide disturbs the subcellular distribution of GABA_A receptor in brain neurons