Ischemia induces metallothionein III expression in neurons of rat brain

Yanagitani, Shingo; Mitsuya, Hiroaki; Nakahashi, Yoshitsugu; Kuno, Kenji; Ueno, Yohji; Matsushita, Makoto; Naitoh, Yasuyuki; Taketani, Shigeru; Inoue, Katsumi

doi:10.1016/s0024-3205(98)00612-2

Cited by 27 publications

(13 citation statements)

References 24 publications

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“…The cellular oxidative stress and acidosis achieved during ischemia may additionally promote the liberation of zinc from zinc-ligands, such as metallothioneins (39,49,64,65). In the attempt to confer resistance to the rising cytosolic zinc levels, the zinc transporter, ZnT-1 and metallothionien III can be upregulated during ischemia to promote zinc efflux and cytosolic buffering, respectively (12,66,67). Zinc also plays an integral role in the subunit expression of Ca-A/K channels during ischemia by altering transcriptional regulation that leads to GluR2 subunit downregulation, the presence of which renders A/K receptor channels calcium-impermeable (20)(21)(22)(23).…”

Section: Resultsmentioning

confidence: 99%

The Role of Zinc in Cerebral Ischemia

Galasso

Dyck

2007

Mol Med

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Ischemic stroke is one of the most pervasive life-threatening neurological conditions for which there currently exists limited therapeutic intervention beyond prevention. As calcium-focused neuroprotective strategies have met with limited clinical success, it is imperative that alternative therapeutic targets be considered in the attempt to antagonize ischemic-mediated injury. As such, zinc, which is able to function both as a signaling mediator and neurotoxin, has been implicated in cerebral ischemia. While zinc was first purported to have a role in cerebral ischemia nearly twenty years ago, our understanding of how zinc mediates ischemic injury is still in its relative infancy. Within this review, we examine some of the studies by which zinc has exerted either neuroprotective or neurotoxic effects during global and focal cerebral ischemia.

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Section: Resultsmentioning

confidence: 99%

The Role of Zinc in Cerebral Ischemia

Galasso

Dyck

2007

Mol Med

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“…In contrast to the MT-3 messenger, the MT-3 protein has been shown to be present mainly in astrocytes by a number of studies (36,40,65,66,(69)(70)(71)(72)(73)(74). Other reports, however, show MT-3 protein presence basically in neurons (63,64,(75)(76)(77). One report demonstrated MT-3 protein not only in neurons, astrocytes and microglia, but also in oligodendrocytes, following lipopolysaccharide (LPS) injection (78).…”

Section: Expression Of Metallothionein-3 In the Central Nervous Systemmentioning

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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“…The antibody does not cross-react with MT-1 or MT-2, which are abundantly localized in the brain and liver. Several antibodies to MT-3 have been reported for immunohistochemical staining (Uchida et al, 1991;Yanagitani et al, 1999;Pang and Ru, 2005), but an ELISA method which is able to determine the MT-3 concentration in clinical and/or experimental specimens has not been reported yet. Therefore, we have developed an ELISA method which may serve as an effective tool for MT-3 research and diagnostic purpose, together with mRNA quantification by RT-PCR (Tsuji et al, 1992;Pang and Ru, 2005;Suzuki et al, 2007;Hozumi et al, 2008;Honda et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…For the detection of MT-3, mRNA measurement by RT-PCR (Erickson et al, 1997;Somji et al, 2004;Suzuki et al, 2007;Haung et al, 2001) and an immunohistochemical staining method using specific antibodies (Uchida et al, 1991;Yanagitani et al, 1999;Pang and Ru, 2005) have been reported. However, a quantitative Determination of metallothionein-3 by a competitive enzyme-linked immunosorbent assay in experimental animals determination by RIA or ELISA has not been reported yet.…”

Section: Introductionmentioning

confidence: 99%

Determination of metallothionein-3 by a competitive enzyme-linked immunosorbent assay in experimental animals

Saito¹,

Nakazato

Kato³

et al. 2013

J. Toxicol. Sci.

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-An easy and specific enzyme-linked immunoassay (ELISA) for the determination of metallothinein-3 (MT-3) in experimental animals for the research of heavy metal and chemical toxicity has not been reported yet. Therefore, we have developed a competitive ELISA, using a specific monoclonal antibody raised against human recombinant MT-3 (rMT-3). The epitope mapping of the antibody was conducted using mouse, rat, and human MT-3s and peptide fragments of human MT-3. MT-1/2, MT-3 knock-out (KO) mice and human brain and liver were used for the evaluation of the ELISA. A pretreatment method of the tissue homogenates was also examined. The antibody used for the ELISA had the same cross-reactivity with MT-3 in humans and experimental animals. The human MT-3 NH 2 terminal peptide (Fr. 1-17) was the demonstrated epitope of this antibody. The reactivity of this ELISA in brain homogenate of MT-3 KO mouse was significantly low compared with the wild type and MT-1/2 KO mice. The lowest detection limit of the ELISA was 10 ng/ml and over 80% of the spiked rMT-3 was recovered in the brain homogenate. The assay linearity was intact with a 5-fold dilution in the brain homogenate. The inter-and intra-assay CV was 6.5%, respectively. An effective pretreatment procedure of the tissue homogenate was also established for this MT-3 ELISA. In conclusion, this competitive ELISA is an easy and specific method for measuring the brain MT-3 level in experimental animals.

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Ischemia induces metallothionein III expression in neurons of rat brain

Cited by 27 publications

References 24 publications

The Role of Zinc in Cerebral Ischemia

The Role of Zinc in Cerebral Ischemia

Metallothioneins and brain injury: What transgenic mice tell us

Determination of metallothionein-3 by a competitive enzyme-linked immunosorbent assay in experimental animals

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