Disease relevance of Mt3

• Expression of growth inhibitory factor (metallothionein-III) mRNA and protein following excitotoxic immature brain injury [1].
• Ischemia induces metallothionein III expression in neurons of rat brain [2].
• In order to confirm the precise localization of MT-III in normal rat brain and the change of MT-III expression after transient whole brain ischemia, we raised a high affinity phagemid-antibody specific for rat MT-III [2].
• The patterns of changes in relative expression levels of GIF and GFAP were quite similar to those in our previous studies on effects of cerebral stab wounds in rats, although the changes were more rapid in the previous studies [3].
• The results indicated that GIF could play an important role in the repair after brain damage and also produce new insights into the mechanism of gliosis investigated mainly from the viewpoint of GFAP [4].

Psychiatry related information on Mt3

• Enhanced neurotrophic activity in Alzheimer's disease cortex is not associated with down-regulation of metallothionein-III (GIF) [5].
• Instead, MT3, a selective antagonist at M(4) receptors, caused amnesia [6].

High impact information on Mt3

• Responses were inhibited by the predominantly MT2-selective antagonist luzindole but not by prazosin, acting at MT3 receptors [7].
• Paradoxically, this unique pool of zinc was eliminated in large-diameter DRG neurons after neonatal capsaicin treatment, which had no effect on selenite stain or MT-III mRNA content in small-diameter DRG neurons [8].
• The distribution of zinc selenite and expression of metallothionein-III mRNA in the spinal cord and dorsal root ganglia of the rat suggest a role for zinc in sensory transmission [8].
• MT-III mRNA, measured using RT-PCR, and MT-III immunoreactivity, were both present in the spinal cord as well as the thoracic and lumbar dorsal root ganglia (DRG) [8].
• We tested the hypothesis that zinc is similarly involved in sensory transmission by determining whether vesicular zinc and metallothionein-III (MT-III), a zinc-binding protein, are localized in rat primary afferent neurons [8].

Chemical compound and disease context of Mt3

• These results suggest that MT-III plays an important role in protecting neurons from ischemic insult by reducing neurotoxic zinc levels and inhibits uncontrolled growth of neurites after ischemia [2].
• The most prominent findings in this study are, a very strong reaction of GIF and GIF mRNA in the reactive astrocytes around the site of injury induced by stab wound or kainic acid injection [9].

Biological context of Mt3

• These results suggest that MT-III down-regulation is not an important pathogenic event in some cases of AD [5].
• A 'silencing element' was revealed within a 250 bp section of the MT III promoter which suppressed gene expression in two brain cell lines [10].
• To investigate the mechanisms underlying its multifaceted roles in the central nervous system, we employed differential display proteomics techniques to study holistic protein changes of PC-12 cells induced by transient transfection of MT-3 [11].
• Isolation, sequencing and functional analysis of the rat MT III genomic locus indicated that, although the organisation of the gene was conserved between MT III and the more conventional metallothioneins, the 5' flanking region of the MT III gene was distinct [10].
• This effect appeared to be independent of the production of second messengers as no specific binding sites for melatonin, including MT1, MT2 and MT3 receptors, could be detected in BAE cells [12].

Anatomical context of Mt3

• MT-I and MT-II are expressed in many tissues, whereas MT-III is expressed exclusively in the central nervous system (CNS) [13].
• In this study, we found that systemic application of kainic acid (KA) rapidly induced MT-I and II expression in neurons localized in hippocampal formation, piriform cortex, and amygdala of the adult rat, whereas the level of MT-III mRNA was decreased in KA-vulnerable areas [14].
• In the present study, high expression of MT-III and MT-I + II genes (examined by RT-PCR and in situ hybridisation) was found in the hippocampus of old rats [15].
• MT-III mRNA was constitutively expressed in rat dental pulp, but the expression level did not change by Cd treatment [16].
• Double immunocytochemical techniques showed GIF (MT-III) and GFAP positive astrocytes from 2-4 hours postinjury [1].

Associations of Mt3 with chemical compounds

• Mt1, Mt2, Mt3 and Mt4 fractions were isolated and reacted with rhodamine-123 [17].
• The melatonin response was abolished by a preceding administration of the antagonists 2-phenylmelatonin and luzindole but was unaffected by the MT3 antagonist prazosin and the MT2 antagonist 4-phenyl-2-propionamidotetralin (4-P-PDOT) [18].
• Neither luzindole, an MT1/MT2 receptor antagonist, nor prazosin, an MT3 receptor antagonist, blocked melatonin-induced current reduction [19].
• During pharmacological screening administration of the agonists 2-iodomelatonin and 2-iodo-N-butanoyl-5-methoxytryptamine (IbMT) to the oocytes resulted in oscillatory membrane currents, whereas the administration of the MT3 agonist 5-methoxycarbonylamino-N-acetyltryptamine (GR135,531) exerted no detectable membrane currents [18].
• In contrast, little or no change in mRNA for metallothionein-III, manganese superoxide dismutase, copper-zinc superoxide dismutase, glutathione-s-transferase ya subunit or glutathione peroxidase occur [20].

Regulatory relationships of Mt3

• Interestingly, most MT in control rat cerebrum and cerebellum was accounted for by MT-III, with MT-I/II being less than 10% [21].

Other interactions of Mt3

• Animals treated with AxCArGIFM showed intense immunolabeling for GIF/Myc in injured facial motoneurons [22].
• Immunohistochemical analysis revealed that MT-III in normal brain is localized abundantly in neuronal cell bodies in CA1-3 regions of hippocampus, dentate gyrus, cerebral cortex, olfactory bulb and Purkinje cells in cerebellum [2].
• We suggest that MT3 may be an intermediate in, or product of, one of the MT/pp60c-src signalling pathways, distinct from that involving pp85 [23].
• Patterns of growth inhibitory factor (GIF) and glial fibrillary acidic protein relative level changes differ following left middle cerebral artery occlusion in rats [3].

Analytical, diagnostic and therapeutic context of Mt3

• Compared with the control group, the stress groups had higher inductions of MTs and MT-1 and MT-3 mRNA in hippocampus [24].
• Because no information is available on this factor in relation to immature brain damage, we examined the chronological changes of GIF (MT-III) mRNA and protein following excitotoxic lesions to the postnatal day 9 brain using in situ hybridization and immunocytochemical techniques [1].
• ELISA and Northern blot analysis revealed that MT-III protein as well as mRNA levels were up-regulated in cerebrum soon after ischemic stress [2].
• In the caput, MT III mRNA levels decreased following orchidectomy, but control levels were maintained by testosterone [25].
• To clarify the biological functions of GIF and GFAP in repair of the CNS, we examined changes in their relative levels to sham control using a Western blotting technique in the rat left hemisphere following occlusion of the left middle cerebral artery, for 28 days after surgery [3].

References