Metallothionein isoforms (I+II and III) and interleukin-6 in the hippocampus of old rats: may their concomitant increments lead to neurodegeneration?

Mocchegiani, Eugenio; Giacconi, Robertina; Fattoretti, Patrizia; Casoli, Tiziana; Cipriano, Catia; Muti, Elisa; Malavolta, Marco; Stefano, Giuseppina Di; Bertoni–Freddari, Carlo

doi:10.1016/j.brainresbull.2004.02.004

Cited by 22 publications

(19 citation statements)

References 51 publications

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“…Recent studies reveal that MTs tend to be highly expressed in both astrocytes and hippocampal neurons in the aging brain (Mocchegiani et al 2004). MTs are strong anti-oxidants and protective factors against stress conditions.…”

Section: Zinc Oxidative Stress and Brain Agingmentioning

confidence: 99%

Oxidative stress and brain aging: is zinc the link?

et al. 2006

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Zn(2+) dyshomeostasis has been strongly linked to neuronal injury in many neurological conditions. Toxic accumulation of intracellular free Zn(2+) ([Zn(2+)](i)) may result from either flux of the cation through glutamate receptor-associated channels, voltage-sensitive calcium channels, or Zn(2+)-sensitive membrane transporters. Injurious [Zn(2+)](i) rises can also result from release of the cation from intracellular sites such as metallothioneins (MTs) and mitochondria. Chronic inflammation and oxidative stress are hallmarks of aging. Zn(2+) homeostasis is affected by oxidative stress, which is a potent trigger for detrimental Zn(2+) release from MTs. Interestingly, Zn(2+) itself is a strong inducer of oxidative stress by promoting mitochondrial and extra-mitochondrial production of reactive oxygen species. In this review, we examine how Zn(2+) dyshomeostasis and oxidative stress might act synergistically to promote aging-related neurodegeneration.

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Section: Zinc Oxidative Stress and Brain Agingmentioning

confidence: 99%

Oxidative stress and brain aging: is zinc the link?

et al. 2006

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“…Carey et al [28] also found induction of the MT synthesis upon the action of a lipopolysaccharide that can be released in abortions and upon the action of teratogenic factors. The metabolism of MTs is very sensitive to humoral/hormonal regulation realized via the action of glucocorticoids, catecholamines, glucagon, steroids, interleukin-6, angiotensin-2, 2-butyl cAMP and phorbol ester, as wee as of stressor factors (proteins of an acute stress phase), and other mediators [29][30][31][32][33][34][35].…”

Section: Regulation Of Mt Metabolismmentioning

confidence: 99%

Peculiarities of the Molecular Structure and Functions of Metallothioneins in the Central Nervous System

Ушакова

Kruchinenko

2009

Neurophysiology

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This review presents modern concepts on the structure and principles of classification of low-molecularweight proteins capable of binding with metal ions, metallothioneins (MTs). The mechanism underlying the binding of metals with these biopolymers is characterized; the main functions of MTs in the CNS, their role in defense reactions of neurons and other cells, as well as of those of the organism in general are reviewed.

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“…The issue of intracellular Zn 2+ buffering is particularly relevant in the context of an ageing brain. Recent findings have in fact indicated that both ageing astrocytes and neurons show increased expression of a class of cytosolic proteins called metallotioneines (MTs; Mocchegiani et al 2004), one of the major systems involved in intracellular Zn 2+ sequestration.…”

Section: Resultsmentioning

confidence: 99%

Acidosis enhances toxicity induced by kainate and zinc exposure in aged cultured astrocytes

2006

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A key feature of cerebral ischemia, one of the leading causes of death associated with ageing, is excessive accumulation of glutamate in the synaptic cleft. In some forms of cerebral ischemia, like transient global ischemia, high levels or synaptic glutamate are complemented by a concomitant increase in extracellular Zn(2+) as result of the release of the cation that is present in the pre-synaptic vesicles of glutamatergic neurons. Interestingly, while neurons are very sensitive to the toxicity triggered by exposure to either glutamate or Zn(2+), astrocytes show less vulnerability to these toxins. We examined the vulnerability of cortical type 1 astrocytes to a combined exposure to the AMPA/kainate receptor agonist kainate and Zn(2+). Astrocytes exposed to 1 mM kainate for 1 h did not exhibit any degeneration in the following 24 h, and addition of 50 microM Zn(2+) to the kainate exposure failed to produce any further glial loss. Another hallmark of cerebral ischemia is parechymal acidosis and therefore, we tested the susceptibility of our cultured astrocytes to a kainate/Zn(2+) exposure performed under acidotic conditions. We found that the combination of 1 h exposure to 1 mM kainate + 50 microM Zn(2+) at pH 6.2 produced a strong increase in intracellular free Zn(2+) ([Zn(2+)](i)), and extensive glial injury. Comparing [Zn(2+)](i) rises triggered by kainate/Zn(2+) exposure at pH 7.4 or pH 6.2 we found that acidosis promotes increased toxic [Zn(2+)](i) levels as a result of a lethal combination of both enhanced Zn(2+) influx through Zn(2+) permeable AMPA/kainate channels and impaired intracellular buffering of the cation.

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Metallothionein isoforms (I+II and III) and interleukin-6 in the hippocampus of old rats: may their concomitant increments lead to neurodegeneration?

Cited by 22 publications

References 51 publications

Oxidative stress and brain aging: is zinc the link?

Oxidative stress and brain aging: is zinc the link?

Peculiarities of the Molecular Structure and Functions of Metallothioneins in the Central Nervous System

Acidosis enhances toxicity induced by kainate and zinc exposure in aged cultured astrocytes

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