Changes in the intracellular accumulation and distribution of metallothionein in rat liver and kidney during postnatal development

Panemangalore, Myna; Banerjee, Diponkar; Onosaka, Satomi; Cherian, M. George

doi:10.1016/0012-1606(83)90067-2

Cited by 182 publications

(68 citation statements)

References 30 publications

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“…Thymuses, livers, kidneys, spleens, and brains (cerebrum, ' A preliminary account of this work was presented at the Society of Toxicology borosilicate test tubes. The mean body weight of a pup was meeting, arch [18][19][20][21][22]1985, in Sari Diego, CA, and was published in "=he calculated by dividing the weight of an entire litter by the number Mean body wt (g) at sacrifice account for differences in organ size in the two treatment grou~s. Analysis of the effect of endotoxin treatment upon the binding of Zn and Cu to MT in liver cytosol followed the procedure of Thomas et al (22).…”

Section: Mt Metallothioneinmentioning

confidence: 99%

“…Thymic growth in endotoxin-treated neonatal mice was examined, because decreased Zn and Cu bioavailability either in utero or in early postnatal life can affect thymic growth and development and diminish immunoresponsiveness (1 4-18). Because the liver is the major depot for both Zn and Cu in the neonate and MT is a major intracellular ligand for these metals in the neonatal liver (19)(20)(21), it was of interest to determine the role of MT induction by endotoxin in the accumulation of these metals in liver and their binding to MT in this organ. …”

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confidence: 99%

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Altered Organ Growth and Zinc and Copper Distribution in Endotoxin-Treated Neonatal Mice

Thomas

Winchurch

1991

Pediatr Res

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Abbreviations essential metals, Zn and Cu. In rats and Syrian hamsters, endotoxin treatment increases Zn and decreases Cu concentrations in liver and decreases Zn and increases Cu concentrations in plasma (6, 7). At the cellular level, endotoxin treatment increases the amount of Zn bound to MT, a cytosolic transition metal-binding protein, in the liver (8) and in cultured hepatocytes (9) and increases the urinary excretion of MT (10). Induction of MT synthesis protects macrophages against endotoxin-induced cell killing (I 1). A distinct 5' regulatory site uniquely responsive to endotoxin modulates MT-I gene transcription in mouse liver and kidney (12).The objective of the present study was to examine changes in tissue growth and Zn and Cu distribution that accompany exposure to endotoxin in early life. Because endotoxin increases MT gene transcription (6, 7) and because this protein sequesters both Zn and Cu intracellularly (13), the possibility that changes in the Zn and Cu distribution among tissues and their binding to MT were associated with endotoxin exposure was investigated. Thymic growth in endotoxin-treated neonatal mice was examined, because decreased Zn and Cu bioavailability either in utero or in early postnatal life can affect thymic growth and development and diminish immunoresponsiveness (1 4-18). Because the liver is the major depot for both Zn and Cu in the neonate and MT is a major intracellular ligand for these metals in the neonatal liver (19)(20)(21), it was of interest to determine the role of MT induction by endotoxin in the accumulation of these metals in liver and their binding to MT in this organ. MATERIALS AND METHODS MT, metallothioneinMale and female HLA/ICR mice (Hill Top Lab Animals, LPS, Serratia marcescens lipopolysaccharide W Scottdale, PA) were paired overnight and maintained with free access to rodent food (Agway, Syracuse, NY) and tap water in a 12 h light-12 h dark photocycle at 23°C. Pregnant females were caged singly before parturition and day of delivery was designated as d 0. Litters were reduced to six pups within 24 h of birth and Endotoxins are complex li~o~ol~saccharides derived from cell pups were always maintained with free access to lactating dams. walls of gram-negative bacteria (1). These toxins have a wide ~p s (no. 3130-35, lot 565368; Difco, Detroit, MI) was disrange of ~a t h o~h~s i o l o g i c effects (2) and play significant roles in solved in physiologic saline and sterilized by filtration immedithe development of circulatory shock (3). These effects are me-ately before use. At 2 d of age, LPS-treated mice received 10 pg diated in part by endotoxin-stimulated production and release of LPS intraperitoneally in 0.05 mL; age-matched control mice of acute phase cytokines (4) and by endotoxin-de~endent mod-received intraperitoneal injections of 0.05 mL of sterile physioulation of glucocorticoid hormone action (5). Endotoxin expo-logic saline. ~t 5, 7, 14, and 28 d of age, LPS-and saline-treated sure also alters the systemic and intracellular metabolism of the...

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Section: Mt Metallothioneinmentioning

confidence: 99%

mentioning

confidence: 99%

Altered Organ Growth and Zinc and Copper Distribution in Endotoxin-Treated Neonatal Mice

Thomas

Winchurch

1991

Pediatr Res

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“…The ontogeny of expression of murine MT showed high amounts of MT-mRNA in visceral and parietal yolk sac [5] and subsequently in developing liver [5, 61. Metallothionein mRNA was also abundant in certain hepatomas and differentiated teratocarcinoma cells [5].The large concentrations of MT present in the early developmental stages correlate with increased hepatic zinc levels [3] suggesting that MT may play a role in the storage of zinc which is required for the rapid fetal and neonatal growth [7, 81. Previous studies provide evidence that maternal zinc status may be one of the important factors which can influence the levels of hepatic zinc and MT in newborn rats [9].…”

mentioning

confidence: 99%

“…The large concentrations of MT present in the early developmental stages correlate with increased hepatic zinc levels [3] suggesting that MT may play a role in the storage of zinc which is required for the rapid fetal and neonatal growth [7, 81. Previous studies provide evidence that maternal zinc status may be one of the important factors which can influence the levels of hepatic zinc and MT in newborn rats [9].…”

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confidence: 99%

Regulation of the ontogeny of rat liver metallothionein mRNA by zinc

Andrews

Gallant

Cherian

1987

European Journal of Biochemistry

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To investigate the role of metals in the regulation of the ontogenic expression of rat liver metallothionein (MT) mRNA, the concentrations of zinc, MT and MT mRNA were determined in livers of fetal and newborn rats from dams whch were fed with a control or zinc-deficient or copper-deficient or iron-deficient diet from day 12 of gestation. The liver samples were analyzed for MT-mRNA levels using a mouse MT-I cRNA probe. Although the newborn hepatic levels of each metal (zinc or copper or iron) was specifically reduced corresponding to the respective mineral deficiencies, the hepatic concentrations of total MT and MT-I mRNA were significantly decreased only in pups born from zinc-deficient dams. Injection of the zinc-deficient newborn pups with 20 mg Zn as ZnS04/kg restored with MT-I mRNA levels to slightly above control values within 5 h of injection. The hepatic zinc, MT and MT-I mRNA levels were observed to increase significantly in control fetal rat liver on days 17-21 of gestation but there were little changes in either zinc or MT in fetal livers from zinc-deficient dams during the late gestational period. The h4T-I mRNA level also did not show an increase on days 18 and 20 of gestation in zinc-deficient fetal liver as compared to controls. These results demonstrate a direct role of zinc in hepatic MT gene expression in rat liver during late gestation. Immunohistochemical localization of MT using a specific antibody to rat liver MT showed that the staining for MT in zinc-deficient pup liver was mainly in the cytosol in contrast to the significant nuclear MT staining observed in control newborn rat liver. The results suggest that maternal zinc deficiency has a marked effect not only in decreasing the levels of hepatic MT and MT-I mRNA but also in the localization of MT in newborn rat liver.The deposition of zinc and the synthesis of metallothionein (MT) in mammalian liver both depend on the stage of development as well as certain changes in physiological conditions. Levels of zinc and MT in rat liver are high during the late fetal and early neonatal periods but decrease dramatially by weaning [l -41. Although there is very little basal synthesis of MT in the livers of control adult animals, synthesis can be induced by injection of certain metals and by various other stress conditions. The ontogeny of expression of murine MT showed high amounts of MT-mRNA in visceral and parietal yolk sac [5] and subsequently in developing liver [5, 61. Metallothionein mRNA was also abundant in certain hepatomas and differentiated teratocarcinoma cells [5].The large concentrations of MT present in the early developmental stages correlate with increased hepatic zinc levels [3] suggesting that MT may play a role in the storage of zinc which is required for the rapid fetal and neonatal growth [7, 81. Previous studies provide evidence that maternal zinc status may be one of the important factors which can influence the levels of hepatic zinc and MT in newborn rats [9].However, the mechanisms of MT gene regulation in fetal and neo...

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“…MT has been reported to be mainly localized in the cytoplasm but also in the nucleus by several investigators (Panemangalore et al 1983; Umeyama et al 1987; Nishi- . Nishimura et al (1990) reported that MT was localized in the nucleus of rat sperm in the testis by an immunohistochemical study.…”

Section: Discussionmentioning

confidence: 98%

Binding of Metallothionein to Rat Spermatozoa.

Suzuki

Nakajima

Yamamoto

et al. 1994

Tohoku J. Exp. Med.

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Binding studies of metallothionein and rat spermatozoa were performed using 125I-Tyr-metallothionein (1251-MT). Reactions between 1251-MT and spermatozoa indicated that MT bound in two forms , namely, middle affinity (Kdl=2 x 10-9 M) binding and low affinity (Kd2=1 x 10_8 M) binding. Labeled MT binding to spermatozoa was inhibited by adding anti-MT antibody. Total binding reactions of MT were temperature and incubation time dependent. By transmission electron microscopy using a gold conjugate (indirect method), gold particles bound to MT were shown to bind to the cell membrane of the head and the proximal portion of the tail. By optical autoradiography, grains of labeled MT were localized mainly in the head and the proximal portion of the tail. By electron microscopical autoradiography, grains of labeled MT were identified mainly in the cell membrane of the head and tail and partly in the nucleus. These results suggest that MT has both specific and non-specific binding sites on the spermatozoal membrane. metallothionein (MT); spermatozoa; autoradiography; transmission electron microscopy Metallothionein (MT) is a metal-binding protein with a low molecular weight of approximately 6,000 and with high cysteine and sulfur content (Margoshes and Vallee 1957). It has been identified in a variety of organs, including the prostate (Waalkes et al. 1982;Bataineh et al. 1986;Umeyama et al. 1987;Suzuki et al. 1991), and binds class II-B metals, such as cadmium and zinc. Zinc is concentrated in the prostatic tissue and secreted into prostatic fluid (Mawson and Fisher

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Changes in the intracellular accumulation and distribution of metallothionein in rat liver and kidney during postnatal development

Cited by 182 publications

References 30 publications

Altered Organ Growth and Zinc and Copper Distribution in Endotoxin-Treated Neonatal Mice

Altered Organ Growth and Zinc and Copper Distribution in Endotoxin-Treated Neonatal Mice

Regulation of the ontogeny of rat liver metallothionein mRNA by zinc

Binding of Metallothionein to Rat Spermatozoa.

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