Discovery of a novel compound: insight into mechanisms for acrylamide-induced axonopathy and colchicine-induced apoptotic neuronal cell death

Nakagawa-Yagi, Yuzo; Choi, Dong‐Kug; Ogane, Nobuo; Shimada, Shin Ichi; Seya, Motohide; Momoi, Takashi; Ito, Takashi; Sakaki, Yoshiyuki

doi:10.1016/s0006-8993(01)02608-7

Cited by 26 publications

(15 citation statements)

References 29 publications

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“…FAK and shRNA expression was monitored through EGFP expression on an IRES of the plasmids. To further investigate whether FAK activation could reduce MICA expression on adherent cells, cells were cultured with the FAK activators acrylamide (26), colchicine, and lysophosphatidic acid (LPA) (27). MICA expression was reduced following treatments with these FAK activators (Figure 6E).…”

Section: Resultsmentioning

confidence: 99%

MICA Expression Is Regulated by Cell Adhesion and Contact in a FAK/Src-Dependent Manner

et al. 2017

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MICA is a major ligand for the NKG2D immune receptor, which plays a key role in activating natural killer (NK) cells and cytotoxic T cells. We analyzed NKG2D ligand expression on a range of cell types and could demonstrate that MICA expression levels were closely linked to cellular growth mode. While the expression of other NKG2D ligands was largely independent of cell growth mode, MICA expression was mainly found on cells cultured as adherent cells. In addition, MICA surface expression was reduced through increase in cell–cell contact or loss of cell–matrix adherence. Furthermore, we found that the reduction in MICA expression was modulated by focal adhesion kinase (FAK)/Src signaling and associated with increased susceptibility to NK cell-mediated killing. While the mechanisms of tumor immune evasion are not fully understood, the reduction of MICA expression following loss of attachment poises a potential way by which metastasizing tumor cells avoid immune detection. The role of FAK/Src in this process indicates a potential therapeutic approach to modulate MICA expression and immune recognition of tumor cells during metastasis.

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Section: Resultsmentioning

confidence: 99%

MICA Expression Is Regulated by Cell Adhesion and Contact in a FAK/Src-Dependent Manner

et al. 2017

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“…The toxic effects of ACR on neurons have been investigated intensively, including the reduction of cell viability, the induction of apoptosis and p53 phosphorylation , , the formation of perikaryal inclusion bodies , and the transduction of neurodegeneration-related signals . Few studies related to glial cells have been reported.…”

Section: Introductionmentioning

confidence: 99%

Proliferation Inhibition, DNA Damage, and Cell-Cycle Arrest of Human Astrocytoma Cells after Acrylamide Exposure

Chen

Tsou

Chiu

et al. 2010

Chem. Res. Toxicol.

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Acrylamide (ACR) has been recognized as a neurological and reproductive toxin in humans and laboratory animals. This study aimed to determine the effects of ACR-induced DNA damage on cell cycle regulation in human astrocytoma cell lines. Treatment of U-1240 MG cells with 2 mM ACR for 48 h resulted in a significant inhibition of cell proliferation as evaluated by Ki-67 protein expression and MTT assay. The analysis of DNA damage with the comet assay showed that treatment of the cells with 0.5, 1, and 2 mM ACR for 48 h caused significant increases in DNA damage by 3.5-, 4-, and 14-fold, respectively. Meanwhile, analysis of cell-cycle arrest with flow cytometry revealed that the ACR treatments resulted in significant increases in the G(0)/G(1)-arrested cells in a time- and dose-dependent manner. Expression of DNA damage-associated/checkpoint-related signaling molecules, including phosphorylated-p53 (pp53), p53, p21, p27, Cdk2, and cyclin D(1), in three human astrocytoma cell lines (U-1240 MG, U-251 MG, and U-87 MG) was also analyzed by immunoblotting. Treatment of the three cell lines with 2 mM ACR for 48 h caused marked increases in pp53 and Cdk2, as well as decreases in cyclin D(1) and p27. Moreover, increases in p53 and p21 were detected in both U-1240 and U-87 MG cells, whereas no marked change in p53 and a decrease in p21 were observed in U-251 MG cells. To address the involvement of ataxia telangiectasia mutated/ATM-Rad3-related (ATM/ATR) kinase in the signaling of ACR-induced G(0)/G(1) arrest, caffeine was used to block the ATM/ATR pathway in U-1240 MG cells. Caffeine significantly attenuated the ACR-induced G(0)/G(1) arrest as well as the expression of DNA damage-associated/checkpoint-related signaling molecules in a dose-dependent manner. This in vitro study clearly demonstrates the critical role of ATM/ATR in the signaling of ACR-induced cell-cycle arrest in astrocytoma cells.

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“…Recently, 3 important hypotheses considering ACR neurotoxicity were suggested: inhibition of kinesin--based fast axonal transport, alteration of neurotransmitter levels, and direct inhibition of neurotransmission [26]. Despite of some researchers believed that exposure of humans to relatively low levels of ACR in the diet will not result in clinical neuropathy [18], some neurotoxicologists are concerned about its cumulative neurotoxicity. It has been shown in several studies that the same neurotoxic effects can be observed at low and high doses of ACR, with the low doses simply requiring longer exposures [32].…”

Section: Discussionmentioning

confidence: 99%

Morphological evaluation of the protective role of dark soy sauce against acrylamide induced neurotoxicity in albino rats

2015

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Discovery of a novel compound: insight into mechanisms for acrylamide-induced axonopathy and colchicine-induced apoptotic neuronal cell death

Cited by 26 publications

References 29 publications

MICA Expression Is Regulated by Cell Adhesion and Contact in a FAK/Src-Dependent Manner

MICA Expression Is Regulated by Cell Adhesion and Contact in a FAK/Src-Dependent Manner

Proliferation Inhibition, DNA Damage, and Cell-Cycle Arrest of Human Astrocytoma Cells after Acrylamide Exposure

Morphological evaluation of the protective role of dark soy sauce against acrylamide induced neurotoxicity in albino rats

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