Regulation of metallothionein‐I+II levels in specific brain areas and liver in the rat: Role of catecholamines

Gasull, Teresa; Giralt, Mercedes; Garcı́a, Agustina; Hidalgo, Juan

doi:10.1002/glia.440120207

Cited by 21 publications

(9 citation statements)

References 32 publications

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“…The present results show for the first time that the widely expressed MT isoforms, MT-I and MT-II, are induced by stress in mouse brain in a time-dependent manner, in agreement with what is known for the rat [13][14][15], presumably acting through increased gene transcrip tion given the close correlation between the MT-I mRNA and the MT-I+II protein levels. In rodents, the expression of the MT-I and MT-II isoforms in a number of condi tions is coordinated [26,27], The effect of stress on liver MT levels has been known for many years [28], but the present and previous [13] results indicate that stress has a general effect on MT(-I+II) expression in the organism.…”

Section: Discussionsupporting

confidence: 72%

“…In previous studies, we have characterized to some extent the MT(-I+II) levels and MT response to stress in up to eight brain areas of the rat [14][15][16][17]29], and have concluded that stress has a general increasing effect on brain MT levels, although different sensitivities appear to exist in different areas [see 29 for further discussion]. The results for MT-I mRNA levels, despite the high variability that often precluded statistically significant results, were actually consistent with what is observed for the MT-I+II protein levels.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, MT-III mRNA levels in the facial motoneu rons decreased after facial nerve transection, which was reported as a specific response to reduce the inhibition of neurite outgrowth in order to regenerate the axons [10]; yet, injury induced by stab wounds or kainic acid injec tion appeared to increase MT-III expression [11,12], Finally, it must be kept in mind that there is no reason to believe that MT-III is more important for the brain than the widely expressed MT-I and MT-II isoforms. These isoforms respond to stress stimuli [13][14][15], are regulated by glucocorticoids [16] and metals [16,17], and are induced heavily by conditions that cause brain injury, such as kainic-induced seizures [18] and freeze lesions [19], which may well be related to the antioxidant proper ties of these proteins [20,21], Thus, from the above data, it seems important to fur ther characterize the regulation not only of MT-III but also that of the 'normal' MT isoforms in the brain. In this report, the response to stress and the putative role of glu cocorticoids are studied in mice and/or rats.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Stress on Mouse and Rat Brain Metallothionein I and III mRNA Levels

et al. 1996

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The effect of immobilization stress on brain and liver metallothionein (MT) mRNA levels has been studied in mice and rats. Stress increased brain and liver MT-I mRNA levels in mice in a time-dependent manner, in agreement with the MT-I+II protein levels, suggesting an increased gene transcription during stress. In contrast, the brain-specific isoform, MT-III, tended to decrease during stress. In selected brain areas of rats, the overall tendency for both MT-I and MT-III mRNA levels was to be transiently decreased by stress in hippocampus, and increased in hypothalamus, cerebellum and the remaining brain tissue; adrenalectomy significantly affected MT mRNA levels either in basal conditions or during stress, with very different temporal patterns of response depending on the brain area studied. These results suggest that glucocorticoids could be involved in MT-I but also MT-III regulation. In both rats and mice, the subtle response to stress observed in the brain contrasts with the robust response in the liver, suggesting that the factors involved in MT regulation in both tissues differ substantially. In primary cultures enriched in astrocytes or neurons, MT-III mRNA was clearly detected by Northern blotting in both cases, suggesting that it is expressed in both types of cells. Dexamethasone appeared to decrease MT-III mRNA levels in cultured neurons and to increase them in astrocytes, which indicates that glucocorticoids have a different role in MT-III regulation in both cell types.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of Stress on Mouse and Rat Brain Metallothionein I and III mRNA Levels

et al. 1996

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“…Thus, significant upregulation of these proteins has been observed in a number of human neurological diseases, including Alzheimer's disease (55,(79)(80)(81)(82)), Pick's disease (79), short-course Creutzfeld-Jakob disease (72), amyotrophic lateral sclerosis (83)(84)(85), and multiple sclerosis (86,87). Experiments carried out in animal models fully demonstrated the response of MT-1&2 to brain damage elicited by inflammatory factors such as lipopolysaccharides (11, 15, 24, 88), stress (62,(89)(90)(91), glutamate analogues (37,51,59,(92)(93)(94)(95), cryogenic injury (28,32,66,71), stroke/ischemia (17, [95][96][97][98], familial amyotrophic lateral sclerosis models (38,67,99,100), multiple sclerosis models (101)(102)(103), and gliotoxins (104)(105)(106).…”

Section: Transgenic Mice Show That Metallothionein-1and2 Are Essential mentioning

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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“…In the spinal cord, the mean microglial densities in the mutant white matter Ž . Ž are about threefold 10-12 days and fivefold [20][21][22] . days higher than in normal animals.…”

Section: Introductionmentioning

confidence: 99%

Induction of metallothionein in astrocytes and microglia in the spinal cord from the myelin-deficient jimpy mouse

et al. 1997

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Jimpy is a shortened life-span murine mutant whose genetic disorder results in severe pathological alterations in the CNS, including Ž . hypomyelination, oligodendrocyte death and strong astroglial and microglial reaction. The knowledge of metallothionein MT regulation in the CNS and especially of MT presence in specific glial cell types under pathological conditions is scarce. In the present study, immunocytochemical detection of MT-I q II has been performed in spinal cord sections from 10-12-and 20-22-day-old jimpy and normal animals. The identification of MT-positive glial cells was achieved through double labeling combining MT immunocytochemistry and selective markers for oligodendrocytes, astrocytes and microglia. MT was found in glial cells and was present in the spinal cord of jimpy and normal mice at both ages, but there were remarkable differences in MT expression and in the nature of MT-positive glial cells depending on the type of mouse. The number of MT-positive cells was higher in jimpy than in normal spinal cords. This was apparent in all spinal cord areas, although it was more pronounced in white than in the gray matter and at 20-22 days than at 10-12 days. The mean Ž . Ž . number of MT-positive glia in the jimpy white matter was 1.9-fold 10-12 days and 2.4-fold 20-22 days higher than in the normal one. Astrocytes were the only parenchymal glial cells that were positively identified as MT-producing cells in normal animals. Interestingly, MT in the jimpy spinal cord was localized not only in astrocytes but also in microglial cells. The occurrence of MT induction in relation to reactive astrocytes and microglia, and its role in neuropathological conditions is discussed. q 1997 Elsevier Science B.V.

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Regulation of metallothionein‐I+II levels in specific brain areas and liver in the rat: Role of catecholamines

Cited by 21 publications

References 32 publications

Effect of Stress on Mouse and Rat Brain Metallothionein I and III mRNA Levels

Effect of Stress on Mouse and Rat Brain Metallothionein I and III mRNA Levels

Metallothioneins and brain injury: What transgenic mice tell us

Induction of metallothionein in astrocytes and microglia in the spinal cord from the myelin-deficient jimpy mouse

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