The possible nuclear compartmentalization of glutathione S-transferase (GST) isoenzymes has been the subject of contradictory reports. The discovery that the dinitrosyl-diglutathionyl-iron complex binds tightly to Alpha class GSTs in rat hepatocytes and that a significant part of the bound complex is also associated with the nuclear fraction (Pedersen, J. Z., De Maria, F., Turella, P., Federici, G., Mattei, M., Fabrini, R., Dawood, K. F., Massimi, M., Caccuri, A. M., and Ricci, G. (2007) 1. BioL Chem. 282, 6364 - 637 1) prompted us to reconsi-der the nuclear localization of GSTs in these cells. Surprisingly, we found that a considerable amount of GSTs corresponding to 10% of the cytosolic pool is electrostatically associated with the outer nuclear membrane, and a similar quantity is compartmentalized inside the nucleus. Mainly Alpha class GSTs, in particular GSTA1-1, GSTA2-2, and GSTA3-3, are involved in this double modality of interaction. Confocal microscopy, immunofluorescence experiments, and molecular modeling have been used to detail the electrostatic association in hepatocytes and liposomes. A quantitative analysis of the membrane-bound Alpha GSTs suggests the existence of a multilayer assembly of these enzymes at the outer nuclear envelope that could represent an amazing novelty in cell physiology. The interception of potentially noxious compounds to prevent DNA damage could be the possible physiological role of the perinuclear and intranuclear localization of Alpha GSTs.

Stella, L., Pallottini, V., Moreno, S., Leoni, S., De Maria, F., Turella, P., et al. (2007). Electrostatic association of glutathione transferase to the nuclear membrane: evidence of an enzyme defense barrier at the nuclear envelope. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 282(9), 6372-6379 [10.1074/jbc.M609906200].

Electrostatic association of glutathione transferase to the nuclear membrane: evidence of an enzyme defense barrier at the nuclear envelope

STELLA, LORENZO;FEDERICI, GIORGIO;FABRINI, RAFFAELE;LO BELLO, MARIO;PEDERSEN, JENS ZACHO;RICCI, GIORGIO
2007-01-01

Abstract

The possible nuclear compartmentalization of glutathione S-transferase (GST) isoenzymes has been the subject of contradictory reports. The discovery that the dinitrosyl-diglutathionyl-iron complex binds tightly to Alpha class GSTs in rat hepatocytes and that a significant part of the bound complex is also associated with the nuclear fraction (Pedersen, J. Z., De Maria, F., Turella, P., Federici, G., Mattei, M., Fabrini, R., Dawood, K. F., Massimi, M., Caccuri, A. M., and Ricci, G. (2007) 1. BioL Chem. 282, 6364 - 637 1) prompted us to reconsi-der the nuclear localization of GSTs in these cells. Surprisingly, we found that a considerable amount of GSTs corresponding to 10% of the cytosolic pool is electrostatically associated with the outer nuclear membrane, and a similar quantity is compartmentalized inside the nucleus. Mainly Alpha class GSTs, in particular GSTA1-1, GSTA2-2, and GSTA3-3, are involved in this double modality of interaction. Confocal microscopy, immunofluorescence experiments, and molecular modeling have been used to detail the electrostatic association in hepatocytes and liposomes. A quantitative analysis of the membrane-bound Alpha GSTs suggests the existence of a multilayer assembly of these enzymes at the outer nuclear envelope that could represent an amazing novelty in cell physiology. The interception of potentially noxious compounds to prevent DNA damage could be the possible physiological role of the perinuclear and intranuclear localization of Alpha GSTs.
2007
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore CHIM/02 - CHIMICA FISICA
Settore BIO/10 - BIOCHIMICA
Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA
English
Con Impact Factor ISI
cells; confocal microscopy; immunology; iron; metal complexes; physiology; cytosolic pools; immunofluorescence; isoenzymes; nuclear fractions; enzyme kinetics; glutathione transferase; glutathione transferase alpha; liposome; membrane enzyme; glutathione S-transferase alpha; glutathione transferase P1; Gstp1 protein, rat; isoenzyme; animal cell; article; cell compartmentalization; cell function; cell nucleus; cell nucleus membrane; confocal microscopy; cytosol; DNA damage; electricity; enzyme analysis; enzyme localization; human; human cell; immunofluorescence; liver cell; male; molecular model; nonhuman; priority journal; protein assembly; protein protein interaction; quantitative analysis; rat; animal; chemistry; enzymology; metabolism; physiology; protein binding; tumor cell line; Wistar rat; rattus; animals; cell line, tumor; electrostatics; glutathione S-transferase pi; glutathione transferase; hepatocytes; humans; isoenzymes; male; nuclear envelope; protein binding; rats; rats, Wistar
Stella, L., Pallottini, V., Moreno, S., Leoni, S., De Maria, F., Turella, P., et al. (2007). Electrostatic association of glutathione transferase to the nuclear membrane: evidence of an enzyme defense barrier at the nuclear envelope. THE JOURNAL OF BIOLOGICAL CHEMISTRY, 282(9), 6372-6379 [10.1074/jbc.M609906200].
Stella, L; Pallottini, V; Moreno, S; Leoni, S; De Maria, F; Turella, P; Federici, G; Fabrini, R; Dawood, K; LO BELLO, M; Pedersen, Jz; Ricci, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/34577
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