![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, MA 02115
A chemical and biochemical mechanism of action of the metallothionein (MT)/thionein (T) couple has been proposed. The mechanism emphasizes the importance of zinc/sulfur cluster bonding in MT and the significance of the two cluster networks as redox units that confer mobility on otherwise tightly bound and redox-inert zinc in MT. In this article, it is further explored how this redox mechanism controls the metabolically active cellular zinc pool. The low redox potential of the sulfur donor atoms in the clusters readily allows oxidation by mild cellular oxidants with concomitant release of zinc. Such a release by oxidants and the preservation of zinc binding by antioxidants place MT under the control of the cellular redox state and, consequently, energy metabolism. The binding of effectors, e.g., ATP, elicits conformational changes and alters zinc binding in MT. The glutathione/glutathione disulfide redox couple as well as selenium compounds effect zinc delivery from MT to the apoforms of zinc enzymes. This novel action of selenium on zinc/sulfur coordination sites has significant implications for the interaction between these essential elements. Tight binding and kinetic lability, modulation of MT by cellular ligands and the redox state, control of MT gene expression by zinc and many other inducers all support a critical function of the MT/T system in cellular homeostasis and distribution of zinc.
KEY WORDS: • zinc • metallothionein • redox regulation • ATP • glutathione
This article has been cited by other articles:
|
|
 |
|
  T. H. Evers, M. A.M. Appelhof, E.W. Meijer, and M. Merkx His-tags as Zn(II) binding motifs in a protein-based fluorescent sensor Protein Eng. Des. Sel., August 1, 2008; 21(8): 529 - 536. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Gyulkhandanyan, H. Lu, S. C. Lee, A. Bhattacharjee, N. Wijesekara, J. E. M. Fox, P. E. MacDonald, F. Chimienti, F. F. Dai, and M. B. Wheeler Investigation of Transport Mechanisms and Regulation of Intracellular Zn2+ in Pancreatic {alpha}-Cells J. Biol. Chem., April 11, 2008; 283(15): 10184 - 10197. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Wiseman, S. M. Wells, M. Hubbard, J. E. Welker, and S. M. Black Alterations in zinc homeostasis underlie endothelial cell death induced by oxidative stress from acute exposure to hydrogen peroxide Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L165 - L177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. J. Kang Metallothionein redox cycle and function. Experimental Biology and Medicine, October 1, 2006; 231(9): 1459 - 1467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Beattie, M.-J. Gordon, M. D. Reid, G. J. Rucklidge, C.-S. Kwon, and I.-S. Kwun Hepatic responses to dietary stress in zinc- and metallothionein-deficient mice. Experimental Biology and Medicine, October 1, 2006; 231(9): 1542 - 1547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Wiseman, S. M. Wells, J. Wilham, M. Hubbard, J. E. Welker, and S. M. Black Endothelial response to stress from exogenous Zn2+ resembles that of NO-mediated nitrosative stress, and is protected by MT-1 overexpression Am J Physiol Cell Physiol, September 1, 2006; 291(3): C555 - C568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Jacob-Wilk, I. Kurek, P. Hogan, and D. P. Delmer The cotton fiber zinc-binding domain of cellulose synthase A1 from Gossypium hirsutum displays rapid turnover in vitro and in vivo PNAS, August 8, 2006; 103(32): 12191 - 12196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Meloni, K. Zovo, J. Kazantseva, P. Palumaa, and M. Vasak Organization and Assembly of Metal-Thiolate Clusters in Epithelium-specific Metallothionein-4 J. Biol. Chem., May 26, 2006; 281(21): 14588 - 14595. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wang, Y. Song, L. Elsherif, Z. Song, G. Zhou, S. D. Prabhu, J. T. Saari, and L. Cai Cardiac Metallothionein Induction Plays the Major Role in the Prevention of Diabetic Cardiomyopathy by Zinc Supplementation Circulation, January 31, 2006; 113(4): 544 - 554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Feng, F. W. Benz, J. Cai, W. M. Pierce, and Y. J. Kang Metallothionein Disulfides Are Present in Metallothionein-overexpressing Transgenic Mouse Heart and Increase under Conditions of Oxidative Stress J. Biol. Chem., January 13, 2006; 281(2): 681 - 687. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Duggan, W. B. MacLeod, N. F. Krebs, J. L. Westcott, W. W. Fawzi, Z. G. Premji, V. Mwanakasale, J. L. Simon, K. Yeboah-Antwi, D. H. Hamer, et al. Plasma Zinc Concentrations Are Depressed during the Acute Phase Response in Children with Falciparum Malaria J. Nutr., April 1, 2005; 135(4): 802 - 807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. R. Starzynski, P. Lipinski, J.-C. Drapier, A. Diet, E. Smuda, T. Bartlomiejczyk, M. A. Gralak, and M. Kruszewski Down-regulation of Iron Regulatory Protein 1 Activities and Expression in Superoxide Dismutase 1 Knock-out Mice Is Not Associated with Alterations in Iron Metabolism J. Biol. Chem., February 11, 2005; 280(6): 4207 - 4212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Martinez-Ruiz and S. Lamas S-nitrosylation: a potential new paradigm in signal transduction Cardiovasc Res, April 1, 2004; 62(1): 43 - 52. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Kindermann, F. Doring, M. Pfaffl, and H. Daniel Identification of Genes Responsive to Intracellular Zinc Depletion in the Human Colon Adenocarcinoma Cell Line HT-29 J. Nutr., January 1, 2004; 134(1): 57 - 62. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. U. Spahl, D. Berendji-Grun, C. V. Suschek, V. Kolb-Bachofen, and K.-D. Kroncke Regulation of zinc homeostasis by inducible NO synthase-derived NO: Nuclear metallothionein translocation and intranuclear Zn2+ release PNAS, November 25, 2003; 100(24): 13952 - 13957. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. P. Kodavanti, A. D. Ledbetter, M. C. Schladweiler, D. L. Costa, C. F. Moyer, R. Hauser, D. C. Christiani, and A. Nyska Reply Toxicol. Sci., July 1, 2003; 74(1): 228 - 229. [Full Text] [PDF]
|
|
|
|
|
|
S. L. Sensi, D. Ton-That, P. G. Sullivan, E. A. Jonas, K. R. Gee, L. K. Kaczmarek, and J. H. Weiss Modulation of mitochondrial function by endogenous Zn2+ pools PNAS, May 13, 2003; 100(10): 6157 - 6162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Abstract Section: 11th International Symposium on Trace Elements in Man and Animals Abstracts J. Nutr., May 1, 2003; 133(5): 203E - 282. [Full Text] [PDF]
|
|
|
|
 |
|
 L.L. Espey, T. Ujioka, H. Okamura, and J.S. Richards Metallothionein-1 Messenger RNA Transcription in Steroid-Secreting Cells of the Rat Ovary During the Periovulatory Period Biol Reprod, May 1, 2003; 68(5): 1895 - 1902. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Richards, S. M. Poch, C. N. Coon, R. W. Rosebrough, C. M. Ashwell, and J. P. McMurtry Feed Restriction Significantly Alters Lipogenic Gene Expression in Broiler Breeder Chickens J. Nutr., March 1, 2003; 133(3): 707 - 715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. K. Lee, J. Geiser, J. Dufner-Beattie, and G. K. Andrews Pancreatic Metallothionein-I May Play a Role in Zinc Homeostasis during Maternal Dietary Zinc Deficiency in Mice J. Nutr., January 1, 2003; 133(1): 45 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Rousset, K. A. Wharton Jr., G. Zimmermann, and M. P. Scott Zinc-dependent Interaction between Dishevelled and the Drosophila Wnt Antagonist Naked Cuticle J. Biol. Chem., December 6, 2002; 277(50): 49019 - 49026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Daiber, D. Frein, D. Namgaladze, and V. Ullrich Oxidation and Nitrosation in the Nitrogen Monoxide/Superoxide System J. Biol. Chem., March 29, 2002; 277(14): 11882 - 11888. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ghoshal, S. Majumder, Q. Zhu, J. Hunzeker, J. Datta, M. Shah, J. F. Sheridan, and S. T. Jacob Influenza Virus Infection Induces Metallothionein Gene Expression in the Mouse Liver and Lung by Overlapping but Distinct Molecular Mechanisms Mol. Cell. Biol., December 15, 2001; 21(24): 8301 - 8317. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Blanchard, J. B. Moore, C. L. Green, and R. J. Cousins Inaugural Article: Modulation of intestinal gene expression by dietary zinc status: Effectiveness of cDNA arrays for expression profiling of a single nutrient deficiency PNAS, November 20, 2001; 98(24): 13507 - 13513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yang, W. Maret, and B. L. Vallee Differential fluorescence labeling of cysteinyl clusters uncovers high tissue levels of thionein PNAS, April 25, 2001; (2001) 101123298. [Abstract] [Full Text]
|
|
|
|
|
|
B. Ye, W. Maret, and B. L. Vallee Zinc metallothionein imported into liver mitochondria modulates respiration PNAS, February 8, 2001; (2001) 41619198. [Abstract] [Full Text]
|
|
|
|
|
|
B. Ye, W. Maret, and B. L. Vallee Zinc metallothionein imported into liver mitochondria modulates respiration PNAS, February 27, 2001; 98(5): 2317 - 2322. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yang, W. Maret, and B. L. Vallee Differential fluorescence labeling of cysteinyl clusters uncovers high tissue levels of thionein PNAS, May 8, 2001; 98(10): 5556 - 5559. [Abstract] [Full Text] [PDF]
|
|
