Up-regulation of Idh3α causes reduction of neuronal differentiation in PC12 cells

Cho, Sun A.; Seo, Min Ji; Ko, Je Yeong; Shim, Jung Hee; Yoo, Jinseon; Kim, Jung Hee; Kim, Se Yoon; Ryu, Na Kyung; Park, Eun Young; Lee, Han Woong; Lee, Yeon Su; Bahk, Young Yil

doi:10.5483/bmbrep.2010.43.5.369

Cited by 3 publications

(1 citation statement)

References 10 publications

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“…Consistent with our data, overexpression of NAD-IDHα has been shown to reduce neuronal differentiation and neurite outgrowth through the inactivation of MAPK phosphorylation in PC12 cells29. Because TBT exposure has been reported to induce neurotoxicity via ERK and p38MAPK phosphorylation in cultured rat cortical neurons30, TBT exposure might cause cytotoxicity through the MAPK pathways.…”

Section: Discussionsupporting

confidence: 89%

NAD-dependent isocitrate dehydrogenase as a novel target of tributyltin in human embryonic carcinoma cells

Yamada

Kotake

Demizu

et al. 2014

Sci Rep

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Tributyltin (TBT) is known to cause developmental defects as endocrine disruptive chemicals (EDCs). At nanomoler concentrations, TBT actions were mediated by genomic pathways via PPAR/RXR. However, non-genomic target of TBT has not been elucidated. To investigate non-genomic TBT targets, we performed comprehensive metabolomic analyses using human embryonic carcinoma NT2/D1 cells. We found that 100 nM TBT reduced the amounts of α-ketoglutarate, succinate and malate. We further found that TBT decreased the activity of NAD-dependent isocitrate dehydrogenase (NAD-IDH), which catalyzes the conversion of isocitrate to α-ketoglutarate in the TCA cycle. In addition, TBT inhibited cell growth and enhanced neuronal differentiation through NAD-IDH inhibition. Furthermore, studies using bacterially expressed human NAD-IDH and in silico simulations suggest that TBT inhibits NAD-IDH due to a possible interaction. These results suggest that NAD-IDH is a novel non-genomic target of TBT at nanomolar levels. Thus, a metabolomic approach may provide new insights into the mechanism of EDC action.

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Section: Discussionsupporting

confidence: 89%

NAD-dependent isocitrate dehydrogenase as a novel target of tributyltin in human embryonic carcinoma cells

Yamada

Kotake

Demizu

et al. 2014

Sci Rep

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Nuclear Akt promotes neurite outgrowth in the early stage of neuritogenesis

Park¹,

Lee²,

Lee³

et al. 2012

BMB Reports

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In addition to its pivotal role in neuronal survival, PI3K/Akt signaling is integral to neuronal differentiation and neurite outgrowth. However, the exact role of Akt in neuronal differentiation is still controversial. Here, we found that nuclear expression of CA-Akt resulted in unusual rapid neurite outgrowth and overexpression of KD-Akt caused multiple dendrite growth without specific axon elongation. Moreover, microarray data revealed that the expression of

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The mRNA quantitative analysis, prokaryotic expression and structure prediction of hepatocarcinogenesis related gene idh3α under AFB1 stress

Zhuang¹

2011

Afr. J. Microbiol. Res.

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By differential proteomics analysis, it was found that the expression level of IDH3 (Isocitrate dehydrogenase 3) in mouse liver was significantly increased under the stress of Aflatoxin B 1. To validate the result of differential proteomics analysis, fluorescence quantitative PCR was used to detect the changing trend of idh3 mRNA volume induced by Aflatoxin B 1 in mouse liver. The result showed that the expression volume of idh3 mRNA showed an increasing trend with the increase of Aflatoxin B 1 concentration, which corresponded with the result of differential proteomics analysis. The protokaryon expression vector for idh3 was constructed in the study with pET28a as a recipient plasmid. The expression vector (pET28a-idh3) was used to transform BL21, after which the positive expression strain (Escherichia coli BL21/pET28a-idh3) was induced to express with 100 mmol/L IPTG under 28°C for 4 h, and the prokaryotic expression product of IDH3 was successfully detected by SDS-PAGE electrophoresis. The molecule structure of IDH3 was predicted by bioinformatics analysis, and the results showed that the total number of negatively and positively charged residues were 42 and 39, respectively. Five hydrohpobic domains were predicted in the protein, and its average hydrophobicity was-0.069. There was 43%-helix and 20%-pleated sheet in the molecule, and the tertiary structure of IDH3 was constituted by 12-helices and 12-pleated sheets. Based on the results of bioinformatics analysis, the fragments of 1-17 and 112-123 residues of IDH3 were selected as candidates for further effective polyclonal antibody preparation. The results of this study paved way for further exploration of the role of idh3 in the process of liver carceration induced by Aflatoxin B 1 .

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Up-regulation of Idh3α causes reduction of neuronal differentiation in PC12 cells

Cited by 3 publications

References 10 publications

NAD-dependent isocitrate dehydrogenase as a novel target of tributyltin in human embryonic carcinoma cells

NAD-dependent isocitrate dehydrogenase as a novel target of tributyltin in human embryonic carcinoma cells

Nuclear Akt promotes neurite outgrowth in the early stage of neuritogenesis

The mRNA quantitative analysis, prokaryotic expression and structure prediction of hepatocarcinogenesis related gene idh3α under AFB1 stress

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