Expression of MT-3 mRNA in human kidney, proximal tubule cell cultures, and renal cell carcinoma

Hoey, John; Garrett, Scott H.; Sens, Mary Ann; Todd, John H.; Sens, Donald A.

doi:10.1016/s0378-4274(97)00049-0

Cited by 81 publications

(56 citation statements)

References 28 publications

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“…Initially regarded as a CNS-specific isoform (11, [40][41][42], it is now clear that MT-3 is expressed in other tissues, in some cases in a development-dependent manner (43)(44)(45)(46)(47)(48)(49). In addition to human and mouse brain, MT-3 has been reported in other species such as horse and cow (50), rat (51), pig (52), dog (53), and sheep (54).…”

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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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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“…Only three isoforms are expressed in the brain, namely MT-I ϩ II (which are also widely expressed and regulated coordinately) and MT-III (also known as growth inhibitory factor). It is now wellestablished that the MT-III isoform is expressed not only in the CNS but also elsewhere (34,41,47). MTs bind zinc and copper and presumably function in metal ion regulation and detoxification in peripheral tissues as well as in the CNS (4,33).…”

Section: Introductionmentioning

confidence: 99%

Metallothioneins Are Upregulated in Symptomatic Mice with Astrocyte-Targeted Expression of Tumor Necrosis Factor-α

Carrasco

Giralt

Penkowa

et al. 2000

Experimental Neurology

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Transgenic mice expressing TNF-␣ under the regulatory control of the GFAP gene promoter (GFAP-TNF␣ mice) exhibit a unique, late-onset chronic-progressive neurological disorder with meningoencephalomyelitis, neurodegeneration, and demyelination with paralysis. Here we show that the metallothionein-I ؉ II (MT-I ؉ II) isoforms were dramatically upregulated in the brain of symptomatic but not presymptomatic GFAP-TNF␣ mice despite TNF-␣ expression being present in both cases. In situ hybridization analysis for MT-I RNA and radioimmunoassay results for MT-I ؉ II protein revealed that the induction was observed in the cerebellum but not in other brain areas. Increased MT-I RNA levels occurred in the Purkinje and granular neuronal layers of the cerebellum but also in the molecular layer. Reactive astrocytes, activated rod-like microglia, and macrophages, but not the infiltrating lymphocytes, were identified as the cellular sources of the MT-I ؉ II proteins. In situ hybridization for MT-III RNA revealed a modest increase in the white matter of the cerebellum, which was confirmed by immunocytochemistry. MT-III immunoreactivity was present in cells which were mainly round or amoeboid monocytes/macrophages. The pattern of expression of the different MT isoforms in the GFAP-TNF␣ mice differed substantially from that described previously in GFAP-IL6 mice, demonstrating unique effects associated with the expression of each cytokine. The results suggest that the MT expression in the CNS reflects the inflammatory response and associated damage rather than a direct role of the TNF-␣ in their regulation and support a major role of these proteins during CNS injury.

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“…Human cerebrum was obtained as an existing biological specimen from the Brain and Tissue Bank for Developmental Tissue Disorders (University of Maryland, Baltimore, MD) and stored at Ϫ80°C. Adult human kidney cortex was obtained as described elsewhere (19,37) and stored at Ϫ80°C. All procurement protocols were approved by the University of North Dakota Institutional Review Board for Human Research.…”

Section: Materials and Reagents-mentioning

confidence: 99%

“…Restoration of this gene causes the cells to dome and exhibit vectorial active transport similar to human proximal tubule cells grown in culture (38). The MT mRNA expression of human proximal tubule cells has been qualitatively evaluated via RT-PCR (19,54,55) and Northern blot analysis (56,57). Combined, these studies paint a broad picture of MT isoform mRNA expression of MT-3, MT-2A, MT-1A, MT-1E, MT-1F, and MT-1X, and possibly of MT-1G.…”

Section: Figmentioning

confidence: 99%

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Quantitation of Human Metallothionein Isoforms: A Family of Small, Highly Conserved, Cysteine-rich Proteins

Mehus

Muhonen

Garrett

et al. 2014

Molecular & Cellular Proteomics

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Human metallothioneins (MTs) are important regulators of metal homeostasis and protectors against oxidative damage. Their altered mRNA expression has been correlated with metal toxicity and a variety of cancers. Current immunodetection methods lack the specificity to distinguish all 12 human isoforms. Each, however, can be distinguished by the mass of its acetylated, cysteine-rich, hydrophilic N-terminal tryptic peptides. These properties were exploited to develop a bottom-up MALDI-TOF/TOF-MS-based method for their simultaneous quantitation. Key features included enrichment of N-terminal acetylated peptides by strong cation exchange chromatography, optimization of C18 reversed-phase chromatography, and control of methionine oxidation. Combinations of nine isoforms were identified in seven cell lines and two tissues. Relative quantitation was accomplished by comparing peak intensities of peptides generated from pooled cytosolic proteins alkylated with 14 N-or 15 N-iodoacetamide. Absolute quantitation was achieved using 15 Niodoacetamide-labeled synthetic peptides as internal standards. The method was applied to the cadmium induction of MTs in human kidney HK-2 epithelial cells expressing recombinant MT-3. Seven isoforms were detected with abundances spanning almost 2 orders of magnitude and inductions up to 12-fold. The protein-to-mRNA ratio for MT-1E was one-tenth that of other MTs, suggesting isoform-specific differences in protein expression efficiency. Differential expression of MT-1G1 and MT-1G2 suggested tissue-and cell-specific alternative splicing for the MT-1G isoform. Protein expression of MT isoforms was also evaluated in human breast epithelial cancer cell lines. Estrogen-receptor-positive cell lines expressed only MT-2 and MT-1X, whereas estrogen-receptor-negative cell lines additionally expressed MT-1E. The combined expression of MT isoforms was 38-fold greater in estrogen-receptornegative cell lines than in estrogen-receptor-positive cells. These findings demonstrate that individual human MT isoforms can be accurately quantified in cells and tissues at the protein level, complementing and expanding mRNA measurement as a means for evaluating MTs as potential biomarkers for cancers or heavy metal toxicity. Molecular & Cellular

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Expression of MT-3 mRNA in human kidney, proximal tubule cell cultures, and renal cell carcinoma

Cited by 81 publications

References 28 publications

Metallothioneins and brain injury: What transgenic mice tell us

Metallothioneins and brain injury: What transgenic mice tell us

Metallothioneins Are Upregulated in Symptomatic Mice with Astrocyte-Targeted Expression of Tumor Necrosis Factor-α

Quantitation of Human Metallothionein Isoforms: A Family of Small, Highly Conserved, Cysteine-rich Proteins

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