The changes of hepatic metallothionein synthesis and the hepatic
damage induced by starvation in mice

Sogawa, Norio; Sogawa, Chiharu; Fukuoka, Hideki; Mukubo, Y.; Yoneyama, Tatsuro; Okano, Yoshiro; Furuta, Hiroaki; Onodera, Kenji

doi:10.1358/mf.2003.25.8.778079

Cited by 10 publications

(7 citation statements)

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“…mtl-1 is a metallothionein gene, which is inducible in response to heavy metal intoxication and stress adaptation [40]. Both rat and mouse mtl genes have been shown to be induced following fasting and may act as an antioxidant in the mouse [45]–[47]. However, metallothioneins have also been proposed to be involved in zinc signalling pathways within mammalian cells [48].…”

Section: Discussionmentioning

confidence: 99%

The Transcriptional Response of Caenorhabditis elegans to Ivermectin Exposure Identifies Novel Genes Involved in the Response to Reduced Food Intake

et al. 2012

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We have examined the transcriptional response of Caenorhabditis elegans following exposure to the anthelmintic drug ivermectin (IVM) using whole genome microarrays and real-time QPCR. Our original aim was to identify candidate molecules involved in IVM metabolism and/or excretion. For this reason the IVM tolerant strain, DA1316, was used to minimise transcriptomic changes related to the phenotype of drug exposure. However, unlike equivalent work with benzimidazole drugs, very few of the induced genes were members of xenobiotic metabolising enzyme families. Instead, the transcriptional response was dominated by genes associated with fat mobilization and fatty acid metabolism including catalase, esterase, and fatty acid CoA synthetase genes. This is consistent with the reduction in pharyngeal pumping, and consequential reduction in food intake, upon exposure of DA1316 worms to IVM. Genes with the highest fold change in response to IVM exposure, cyp-37B1, mtl-1 and scl-2, were comparably up-regulated in response to short–term food withdrawal (4 hr) independent of IVM exposure, and GFP reporter constructs confirm their expression in tissues associated with fat storage (intestine and hypodermis). These experiments have serendipitously identified novel genes involved in an early response of C. elegans to reduced food intake and may provide insight into similar processes in higher organisms.

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Section: Discussionmentioning

confidence: 99%

The Transcriptional Response of Caenorhabditis elegans to Ivermectin Exposure Identifies Novel Genes Involved in the Response to Reduced Food Intake

et al. 2012

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“…(32) to be the major MT isoform elevated in response to stress induced by sodium arsenite which is what we found in our present study, although the type of stress is different. Moreover, positive association of MT and starvation has also been reported in vivo (33).…”

Section: Discussionmentioning

confidence: 84%

Modulation of metallothionein isoforms is associated with collagen deposition in proliferating keloid fibroblasts in vitro

Toh

Yip

et al. 2010

Experimental Dermatology

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The keloid fibroblast (KF) is known to have higher proliferative capacity than normal dermal fibroblast (NF). Metallothionein (MT), a metal-binding protein, has been reported to promote cell proliferation. In this study, we evaluated the expression of MT isoforms at the mRNA level in fetal bovine serum (FBS)-stimulated proliferating KF. Although the morphological appearance of NF and KF was similar when viewed under light, confocal and transmission electron microscopy, there was surprisingly a generally lower expression of MT isoforms in KF when compared with NF and also reduced MT staining in dermal fibroblasts of keloids as opposed to normal skin. Primary cultures of KF grown in 5% FBS or 10% FBS compared to without FBS demonstrated significantly higher proliferative activity and more abundant deposition of collagen. Contrary to expectation, MT-1A, -1F, -1G, -1X and -2A isoforms were significantly down-regulated in proliferating KF. Moreover, stimulating KF with TGF β1, which is known to promote collagen synthesis and keloid formation, increased expression of Collagen 1A and 3A genes accompanied by reduction in MT-2A gene expression. Furthermore, down-regulation of the MT-2A gene in proliferating KF by siRNA-mediated silencing enhanced cell proliferation with concomitant up-regulation of the NF-κB gene and 10 of 13 other NF-κB pathway-related genes analysed but no alteration of the Collagen 1 and Collagen 3 gene expression. It would appear that down-regulation of MT isoforms in proliferating KF, in particular MT-2A, enhances keloidogenesis with the possible involvement of the NF-κB signalling pathway.

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“…Additionally, Kondoh et al (2002) have used a cadmium-binding assay to show that a short-term (24 hr.) fasting period dramatically increases MT protein abundance in liver tissue of ICR, BALB/C and C3H mice, and induction of hepatic MT synthesis by starvation was also confirmed by Sogawa et al (2003). With regard to mouse liver, therefore, elevated expression of Mt genes and increased MT protein following reduction of caloric intake have been demonstrated using both genomic and non-genomic methodologies.…”

Section: Regulation Of Metallothionein By Caloric Intakementioning

confidence: 88%

Metallothionein and the biology of aging

Swindell

2011

Ageing Research Reviews

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Metallothionein (MT) is a low molecular weight protein with anti-apoptotic properties that has been demonstrated to scavenge free radicals in vitro. MT has not been extensively investigated within the context of aging biology. The purpose of this review, therefore, is to discuss findings on MT that are relevant to basic aging mechanisms and to draw attention to the possible role of MT in pro-longevity interventions. MT is one of just a handful of proteins that, when overexpressed, has been demonstrated to increase mouse lifespan. MT also protects against development of obesity in mice provided a high fat diet as well as diet-induced oxidative stress damage. Abundance of MT is responsive to caloric restriction (CR) and inhibition of the insulin / insulin-like signaling (IIS) pathway, and elevated MT gene expression has been observed in tissues from fasted and CR-fed mice, long-lived dwarf mice, worms maintained under CR conditions, and long-lived daf-2 mutant worms. The dysregulation of MT in these systems is likely to have tissue-specific effects on aging outcomes. Further investigation will therefore be needed to understand how MT contributes to the response of invertebrates and mice to CR and the endocrine mutations studied by aging researchers.

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The changes of hepatic metallothionein synthesis and the hepatic damage induced by starvation in mice

Cited by 10 publications

References 0 publications

The Transcriptional Response of Caenorhabditis elegans to Ivermectin Exposure Identifies Novel Genes Involved in the Response to Reduced Food Intake

The Transcriptional Response of Caenorhabditis elegans to Ivermectin Exposure Identifies Novel Genes Involved in the Response to Reduced Food Intake

Modulation of metallothionein isoforms is associated with collagen deposition in proliferating keloid fibroblasts in vitro

Metallothionein and the biology of aging

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