Fast Axonal Transport: A Site of Acrylamide Neurotoxicity?

Sickles, Dale W.; Stone, J. D.; Friedman, Marvin A.

doi:10.1016/s0161-813x(02)00025-6

Cited by 73 publications

(46 citation statements)

References 158 publications

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“…nocodazole and latrunculin. Numerous studies have reported inhibitory effects of ACR on both anterograde and retrograde axonal transport in many different systems [reviewed by Sickles et al, 2002]. Microtubules are potential sites of action since axonal transport is completely dependent upon these structures.…”

Section: Discussionmentioning

confidence: 99%

“…Normal axonal transport is important in maintaining neuronal viability and a very recent review highlights the fact that impairment in transport may be the cause of neurodegenerative diseases like Alzheimer's disease [Morfini et al, 2005]. An extensive review by Sickles et al [2002] summarizes the studies made on the effects of ACR on axonal transport in order to establish the molecular site and mechanism of action by which ACR causes neurotoxicity.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

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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“…Typical pathologic consequences induced by ACR are known to include distal swelling and eventual degeneration of axons, and it has been classified either as a central-peripheral distal axonopathy, distal sensorimotor, symmetrical polyneuropathy, neurofilamentous axonopathy, or dying-back neuropathy [1,3].…”

Section: Introductionmentioning

confidence: 99%

“…Many years of research have provided a large amount of information describing the ACR neurotoxicity mechanism [1]. However, there is still a debate regarding the causal relationship of the ACR neurotoxicity mechanism underlying the characteristic neurological defects [4,5].…”

Section: Introductionmentioning

confidence: 99%

Effect of subchronic acrylamide exposure on the expression of neuronal and inducible nitric oxide synthase in rat brain

Kim

2005

J Biochem & Molecular Tox

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Acrylamide (ACR) is a known industrial neurotoxic chemical. Evidence suggests that ACR neurotoxic effect is related to brain neurotransmission disturbances. Since nitric oxide (NO) acts as a neurotransmission modulator and is produced by nitric oxide synthase (NOS), the neuronal NOS (nNOS) and inducible NOS (iNOS) expression pattern were determined in rat cerebral cortex and striatum after subchronic exposure to ACR. Using immunocytochemistry, the neuronal count of nNOS or optical density of iNOS from sections at three coronal levels, bregma 1.0, -0.4, and -2.3 mm, were compared between ACR-treated and control rats. At all three levels, nNOS expressions were uniformly decreased in most of the neocortical subregions following the treatment of ACR. At bregma level 1.0 mm, total numbers of nNOS expressing neurons were significantly decreased to 58.7% and 64.7% of the control in the cortex and striatum of ACR-treated rats, respectively. However, at the bregma level -2.3 mm, ACR treatment did not produce a significant difference in the numbers of nNOS expressing neurons both in the cortex and striatum. Contrary to nNOS, iNOS expressions were consistently increased to approximately 32% in the neocortex and 25% in the striatum, following the subchronic ACR treatment. These data suggest that subchronic ACR exposure involves compensatory mechanism on nNOS and iNOS expression to maintain the homeostasis of NO at the rostral part of the neocortex and the striatum. However, in the caudal brain, increased iNOS expression did not suppress nNOS expression. Therefore, the present study is consistent with the hypothesis that ACR toxicity is mediated through the disturbance to the NO signaling pathway and exhibits a rostrocaudal difference through the differential expressions of nNOS and iNOS in the neocortex and the striatum.

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“…ACR can suppress metabolism and axonal transport in neurons which leads to a deficiency of nutritional factors [15]. ACR shows its toxic effect on both central nervous system and peripheral nervous system [16]. Both oxidative stress and apoptosis play a key role in ACR-induced toxicity [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Determination of acrylamide-induced chick embryo brain glutathione S-transferases expression through enzyme activity and western blot

2018

J App Biol Biotech

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Glutathione S-transferases (GSTs) are major detoxification enzymes which belong to Phase II defense enzymes; they can able to metabolize a variety of toxic chemical agents such as carcinogens, genotoxins, neurotoxins, and pesticides. Usually, GST will express when the living beings are encountered toxic chemical compounds. Acrylamide (ACR) is synthesized industrially and widely used in various industries. Usually, ACR formation occurs when food products prepared at high temperature. So that ACR is an environmental and food contaminant and it is well-proven neurotoxin. Due to highly mobile nature, birds that include poultry birds are main victims to xenobiotics (e.g., ACR) through food, water, and agricultural chemical formulas. In this study, ACR administered chick embryo brain GST activity level was assayed using 1-chloro-2,4-dinitrobenzene, and expression was assessed by western blot studies. The results show that the GST expression levels were increased in response to ACR by 24 and 48 h intervals. However, in 48 h interval, GST expression levels decreased slightly. Western blot studies also show similar pattern of GST expression. Immune blot studies showed similar GST band pattern as purification studies showed (our published work). In this study, enzyme activity and western blot analysis proved that the chick embryo brain GST was expressed more to detoxify ACR.

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Fast Axonal Transport: A Site of Acrylamide Neurotoxicity?

Cited by 73 publications

References 158 publications

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

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

Effect of subchronic acrylamide exposure on the expression of neuronal and inducible nitric oxide synthase in rat brain

Determination of acrylamide-induced chick embryo brain glutathione S-transferases expression through enzyme activity and western blot

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