Changes of growth inhibitory factor after stab wounds in rat brain

Hozumi, Isao; Ishii, Takashi; Hiraiwa, Masao; Uchida, Yuzo; Anezaki, Toshiharu; Ishiguro, Hisaaki; Kobayashi, Hisashi; Uda, Yutaka; Miyatake, Tadashi; Tsuji, Shoji

doi:10.1016/0006-8993(95)00522-r

Cited by 72 publications

(31 citation statements)

References 18 publications

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“…has been observed in animal models of brain injury. Thus, MT-3 expression has been increased by stab wounds (56,70,136) and kainic acid administration (56), but decreased by cortical ablation of the somatosensory cortex (57), facial nerve transection (58), and middle cerebral artery occlusion (137). A biphasic response of MT-3 to CNS injury, with initial downregulation followed by upregulation, was observed in response to N-methyl-D-aspartate (NMDA) (65) or to a cryolesion (66, 125).…”

Section: Transgenic Mice Show Different Metallothionein-3 Functionsmentioning

confidence: 99%

Metallothioneins and brain injury: What transgenic mice tell us

Hidalgo

2004

Environ Health Prev Med

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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.

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Section: Transgenic Mice Show Different Metallothionein-3 Functionsmentioning

confidence: 99%

Metallothioneins and brain injury: What transgenic mice tell us

Hidalgo

2004

Environ Health Prev Med

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“…In these studies, the effect of free zinc on the bioactivity could be excluded. In addition, changes in MT-3 mRNA levels in response to central nervous system injury have been taken to indicate an important role of the protein in brain repair (14,15). In this context, it should be noted that MT-3-deficient mice showed no neuropathology under normal conditions but a higher susceptibility to seizures induced by kainic acid (16).…”

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confidence: 99%

Engineering of Metallothionein-3 Neuroinhibitory Activity into the Inactive Isoform Metallothionein-1

Romero‐Isart

Jensen

Zerbe

et al. 2002

Journal of Biological Chemistry

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The third isoform of mammalian metallothioneins (MT-3), mainly expressed in brain and down-regulated in Alzheimer's disease, exhibits neuroinhibitory activity in vitro and a highly flexible structure that distinguishes it from the widely expressed MT-1/-2 isoforms. Previously, we showed that two conserved prolyl residues of MT-3 are crucial for both the bioactivity and cluster dynamics of this isoform. We have now used genetic engineering to introduce these residues into mouse MT-1. The S6P,S8P MT-1 mutant is inactive in neuronal survival assays. However, the additional introduction of the unique Thr5 insert of MT-3 resulted in a bioactive MT-1 form. Temperature-dependent and saturation transfer 113 Cd NMR experiments performed on the 113 Cd-reconstituted wild-type and mutant Cd 7 -MT-1 forms revealed that the gain of MT-3-like neuronal inhibitory activity is paralleled by an increase in conformational flexibility and intersite metal exchange in the N-terminal Cd 3 -thiolate cluster. The observed correlation suggests that structure/cluster dynamics are critical for the biological activity of MT-3. We propose that the interplay between the specific Pro-induced conformational requirements and those of the metal-thiolate bonds gives rise to an alternate and highly fluctuating cluster ensemble kinetically trapped by the presence of the 5 TCPCP 9 motif. The functional significance of such heterogeneous cluster ensemble is discussed.

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“…[1][2][3][4][5][6]8) Recently, another role, protection against critical tissue injury and tissue repair, has been proposed. 9,10) The significance of the MT-IV isoform has yet to be established.…”

Section: Four Mt Isoforms Have Been Identified: Mt-i Mt-ii Mt-iii mentioning

confidence: 99%

“…42) In humans, the serum catalase and superoxide dismutase (SOD) activities were enhanced and the GSH level was increased with the addition of PM to DA, compared with DA alone. 44) Although MT-I has antioxidative properties 1,2,8) and MT-III might be associated with tissue repair, 9,10) the effects of PM on MT induction have not been reported.…”

Section: Fig 2 Body Weight Changementioning

confidence: 99%

“…5). The MT-III isoform is supposed to serve a role in tissue repair and protection against critical tissue injury 9,10,34) as well as in zinc storage. [3][4][5][6] Taking these aspects into account, the resistance to MPTP treatment and the tendency toward upregulation after PM administration following MPTP treatment seem reasonable and acceptable.…”

Section: Fig 2 Body Weight Changementioning

confidence: 99%

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