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Chemical Compound Review:

TPEN N,N,N',N'-tetrakis(pyridin- 2...

Synonyms: SureCN231092, AG-K-40969, BSPBio_001186, KBioGR_000526, KBioSS_000526, ...

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Disease relevance of KBio2_005662

DNA microarrays were used to probe the transcriptional response of Escherichia coli to N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) [1].
Even though N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) has a higher affinity for Cu+2 than for Zn+2, TPEN had no effect on the toxicity of Cu+2 while totally preventing damage caused by Fe+3 or Zn+2 [2].
Treatment of breast cancer cells with different concentrations of a cell membrane permeable zinc chelator, N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) and the membrane impermeable zinc chelator, diethylenetriaminepentacetic acid, (DTPA) resulted in a significant increase of cell death [3].

High impact information on KBio2_005662

Treatment of cells with TPEN (N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine), a Zn(2+)-binding drug, resulted in a dramatic redistribution and translocation of S100B [4].
By using a new lipid-soluble heavy metal chelator TPEN (N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine), which crosses artificial and natural membranes, it was found that endogenous heavy metals are responsible for partially quenching quin-2 fluorescence trapped inside the cells [5].
The zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine augmented the activity of wild-type PHD2-F but not that of PHD2 lacking the MYND domain, confirming that the zinc finger domain is inhibitory [6].
Vice versa, specific chelation of cellular zinc with the membrane-permeable N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine suppresses insulin- and IGF-1-stimulated phosphorylation [7].
RESULTS: The apoptotic response of RPE cells was markedly enhanced when TNF-alpha plus actinomycin D (act-D) was coapplied with N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), a heavy metal ion chelator [8].

Biological context of KBio2_005662

To investigate the mechanisms of zinc depletion-induced apoptosis, HeLa cells were treated with the membrane permeable metal ion chelator, N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) [9].
Zn2+ (50-200 microM) showed a synergistic effect on platelet aggregation and platelet release caused by ADP and N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine, a Zn2+ chelator, and inhibited ADP-induced platelet aggregation that was reversed by Zn2+ (50 microM) [10].
Removal of N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine from culture medium allowed p53 to refold into the immunologically wild-type form, followed by a transient increase in DNA binding, expression of the cyclin-dependent kinase inhibitor p21WAF1, and cell-cycle delay in the G1 phase [11].
The stimulatory effects of zinc or H2O2 on MTA, MTB, GST, and G6PD mRNA levels could be blocked by addition of the membrane permeable zinc chelator, N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), suggesting that H2O2-induced upregulation of these genes is zinc-dependent [12].
We have observed that this form of LTP could be induced in the presence of the permeant heavy metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) and that application of this chelator, during LTP, caused an enhancement of the presynaptic calcium signals without affecting synaptic transmission [13].

Anatomical context of KBio2_005662

No Zn2+ peak was observed in synaptosomes treated with the cell-permeant heavy metal chelator N,N,N',N'-tetrakis(2- pyridylmethyl)ethylenediamine (TPEN, 100 microM) following 250 microM MeHg exposure [14].
Observations by fluorescence microscopy and photoelectron microscopy indicated that pretreatment with the transition metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) for 1-2 h at 50 microM reduced the sensitivity of the actin cytoskeleton to disruption by the subsequent addition of 200 nM phorbol myristate acetate (PMA) [15].
Effects of the heavy metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) were investigated on cytotoxicity in clonal NG108-15 neuroblastoma-glioma hybrid cells [16].

Associations of KBio2_005662 with other chemical compounds

Both desferrioxamine and N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine, two structurally different iron chelators, significantly reduced H2O2-induced neuronal death under both pH 7.2 and pH 6.2 conditions [17].
However, superfusion with N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), or dithiothreitol (DTT), two membrane-permeant heavy metal chelators, rapidly diminished fluorescence, suggesting that the increase in TSQ fluorescence was caused by an intracellular increase in free Zn2+ [18].
The EPSC was reduced in all cells by the NR1/NR2B-selective antagonist ifenprodil, and the Zn(2+) chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) produced a transient potentiation in 50% of cells [19].
Fluorescence quenching by the heavy metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine was used to quantitate [Zn2+]i. The thiol-reactive oxidants hypochlorous acid (0.1 mM) and selenite (1 mM) increased [Zn2+]i to 7.7 +/- 1.7 and 6.1 +/- 1.7 nM, respectively, within 5 min [20].

Gene context of KBio2_005662

N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine inhibits ligand binding to certain G protein-coupled receptors [21].

Analytical, diagnostic and therapeutic context of KBio2_005662

The crystal structure of zinc complex with TQEN was determined by X-ray crystallography and compared with that of the TPEN-Zn complex (TPEN =N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine) [22].

References

Transcriptional response of Escherichia coli to TPEN. Sigdel, T.K., Easton, J.A., Crowder, M.W. J. Bacteriol. (2006) [Pubmed]
Comparative effects of metal chelating agents on the neuronal cytotoxicity induced by copper (Cu+2), iron (Fe+3) and zinc in the hippocampus. Armstrong, C., Leong, W., Lees, G.J. Brain Res. (2001) [Pubmed]
Cytotoxic effects of intra and extracellular zinc chelation on human breast cancer cells. Hashemi, M., Ghavami, S., Eshraghi, M., Booy, E.P., Los, M. Eur. J. Pharmacol. (2007) [Pubmed]
Intracellular Ca2+ and Zn2+ levels regulate the alternative cell density-dependent secretion of S100B in human glioblastoma cells. Davey, G.E., Murmann, P., Heizmann, C.W. J. Biol. Chem. (2001) [Pubmed]
Cytosolic Ca2+ homeostasis in Ehrlich and Yoshida carcinomas. A new, membrane-permeant chelator of heavy metals reveals that these ascites tumor cell lines have normal cytosolic free Ca2+. Arslan, P., Di Virgilio, F., Beltrame, M., Tsien, R.Y., Pozzan, T. J. Biol. Chem. (1985) [Pubmed]
Inhibition of the catalytic activity of hypoxia-inducible factor-1alpha-prolyl-hydroxylase 2 by a MYND-type zinc finger. Choi, K.O., Lee, T., Lee, N., Kim, J.H., Yang, E.G., Yoon, J.M., Kim, J.H., Lee, T.G., Park, H. Mol. Pharmacol. (2005) [Pubmed]
Intracellular zinc fluctuations modulate protein tyrosine phosphatase activity in insulin/insulin-like growth factor-1 signaling. Haase, H., Maret, W. Exp. Cell Res. (2003) [Pubmed]
Mechanisms of apoptosis in human retinal pigment epithelium induced by TNF-alpha in conditions of heavy metal ion deficiency. Yang, J.H., Le, W.D., Basinger, S.F., Wu, S.M., Yang, C.Y. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
Role of cellular zinc in programmed cell death: temporal relationship between zinc depletion, activation of caspases, and cleavage of Sp family transcription factors. Chimienti, F., Seve, M., Richard, S., Mathieu, J., Favier, A. Biochem. Pharmacol. (2001) [Pubmed]
Exposure of platelet fibrinogen receptors by zinc ions: role of protein kinase C. Trybulec, M., Kowalska, M.A., McLane, M.A., Silver, L., Lu, W., Niewiarowski, S. Proc. Soc. Exp. Biol. Med. (1993) [Pubmed]
Modulation of p53 protein conformation and DNA-binding activity by intracellular chelation of zinc. Verhaegh, G.W., Parat, M.O., Richard, M.J., Hainaut, P. Mol. Carcinog. (1998) [Pubmed]
ZINC-mediated gene expression offers protection against H2O2-induced cytotoxicity. Chung, M.J., Walker, P.A., Brown, R.W., Hogstrand, C. Toxicol. Appl. Pharmacol. (2005) [Pubmed]
Hippocampal mossy fiber calcium transients are maintained during long-term potentiation and are inhibited by endogenous zinc. Quinta-Ferreira, M.E., Matias, C.M. Brain Res. (2004) [Pubmed]
Methylmercury-induced elevations in intrasynaptosomal zinc concentrations: an 19F-NMR study. Denny, M.F., Atchison, W.D. J. Neurochem. (1994) [Pubmed]
Transition metal chelator TPEN counteracts phorbol ester-induced actin cytoskeletal disruption in C6 rat glioma cells without inhibiting activation or translocation of protein kinase C. Hedberg, K.K., Birrell, G.B., Mobley, P.L., Griffith, O.H. J. Cell. Physiol. (1994) [Pubmed]
Cytotoxic actions of the heavy metal chelator TPEN on NG108-15 neuroblastoma-glioma cells. Adler, M., Shafer, H., Hamilton, T., Petrali, J.P. Neurotoxicology (1999) [Pubmed]
Acidosis potentiates oxidative neuronal death by multiple mechanisms. Ying, W., Han, S.K., Miller, J.W., Swanson, R.A. J. Neurochem. (1999) [Pubmed]
Hypochlorous acid mobilizes intracellular zinc in isolated rat heart myocytes. Tatsumi, T., Fliss, H. J. Mol. Cell. Cardiol. (1994) [Pubmed]
NMDA receptor-mediated currents in rat cerebellar granule and unipolar brush cells. Billups, D., Liu, Y.B., Birnstiel, S., Slater, N.T. J. Neurophysiol. (2002) [Pubmed]
Oxidants increase intracellular free Zn2+ concentration in rabbit ventricular myocytes. Turan, B., Fliss, H., Désilets, M. Am. J. Physiol. (1997) [Pubmed]
N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine inhibits ligand binding to certain G protein-coupled receptors. Webster, J.M., Bentley, M.T., Wojcikiewicz, R.J. Eur. J. Pharmacol. (2003) [Pubmed]
Tetrakis(2-quinolinylmethyl)ethylenediamine (TQEN) as a new fluorescent sensor for zinc. Mikata, Y., Wakamatsu, M., Yano, S. Dalton transactions (Cambridge, England : 2003) (2005) [Pubmed]

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