Metallothioneins and brain injury: What transgenic mice tell us

Abstract

In rodents, the metallothionein (MT) family is composed of four members, MT-1 to MT-4. MT-1&2 are expressed in virtually all tissues including those of the Central Nervous System (CNS), while MT-3 (also called Growth Inhibitory Factor) and MT-4 are expressed prominently in the brain and in keratinizing epithelia, respectively. For the understanding of the physiological functions of these proteins in the brain, the use of transgenic mice has provided essential information. Results obtained in MT-1&2-null mice and in MT-1-overexpressing mice strongly suggest that these MT isoforms are important antioxidant, anti-inflammatory and antiapoptotic proteins in the brain. Results in MT-3-null mice show a very different pattern, with no support for MT-1&2-like functions. Rather, MT-3 could be involved in neuronal sprouting and survival. Results obtained in a model of peripheral nervous system injury also suggest that MT-3 could be involved in the control of nerve growth.

Specificity and divergence in the neurobiologic effects of different metallothioneins after brain injury

“…It has been established clearly that MT‐II administered exogenously induces neuroprotection in a number of injury models as long as the BBB is altered (Penkowa and Hidalgo, 2000, 2001; Giralt et al, 2002b; Chung et al, 2003; Xie et al, 2004). It is generally agreed that mammalian MT‐I and MT‐II will likely be functionally equivalent, and in fact results obtained in Mt1&2 KO mice are consistent with those obtained in mice overexpressing MT‐I regarding brain neurobiology (Hidalgo et al, 2001; Hidalgo, 2004). Nevertheless, direct comparative studies validating this have not been carried out.…”

Evidence for noncooperative metal binding to the α domain of human metallothionein

“…The high capacity of MT to bind both essential and nonessential metal ions in vivo and in vitro strongly suggests a role in metal ion storage, metabolism and trafficking of Cu and Zn, as well as sequestration of Cd and Hg; however, the exact function of MT remains undefined. More recently, MT has been implicated in brain tissue repair through anti-inflammatory, antioxidant and antiapoptotic roles [7][8][9][10][11], as well as in chemotherapy resistance [12]. Domain-independent but metal ion-directed folding of MT results in the formation of discrete metalthiolate clusters within each of the a and b domains with stoichiometries of [M 4 (S cys ) 11 ] and [M 3 (S cys ) 9 ], respectively, for divalent metal ions (M) [13][14][15].…”

Estudo das relações entre populações celulares, expressão de aquaporina-4 e sulfato de condroitina com o tempo de relaxamento e a taxa de transferência de magnetização no hipocampo de pacientes com epilepsia do lobo temporal farmacorresistente

“…In TLE-TD group, MT-I/II expression correlated positively with neuronal population only in CA4. In the CNS, MT-I/II are expressed mainly by astrocytes [46] and, when the tissue suffers an injury, increased MT-I/II expression is observed in astrocytes and microglias [46], [32]. In our study, an increased expression of MT-I/II was observed in astrocytes and Figure 5.…”