The Involvement of Catecholamines and Polypeptide Hormones in the Multihormonal Modulation of Rat Hepatic Zinc Thionein Levels

Brady, F.; Helvig, Bethany S.; Funk, Allen E.; Garrett, Scott H.

doi:10.1007/978-3-0348-6784-9_57

Cited by 10 publications

(2 citation statements)

References 17 publications

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“…It is clear that MT synthesis is vital for hepatic Zn sequestration in starvation. Catecholamine release [24], accentuated by handling stress, may have also contributed to MT synthesis in the normal mice.…”

Section: Discussionmentioning

confidence: 99%

Endotoxin-induced inflammation does not cause hepatic zinc accumulation in mice lacking metallothionein gene expression

Philcox

Coyle

Michalska

et al. 1995

Biochemical Journal

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The action of endotoxin lipopolysaccharide (LPS) on hepatic Zn uptake was examined in mice lacking expression of metallothionein (MT)-1 and MT-II genes. Hepatic Zn concentrations, which in normal control mice increased by a mean 29% (MT elevated 20-fold) 16 h post-LPS exposure, did not increase in MT-null mice. Plasma Zn fell by 68% in controls and 32% in MT-null mice. The time course of LPS action in normal mice was characterized by a rapid reduction (-74% at 4 h, -81% at 8 h) and partial recovery (-39% at 24 h) in plasma Zn, with a progressive increase over 24 h in hepatic concentrations of MT (by 36-fold) and Zn (by 40%). In contrast, the MT-null mice had a linear decrease in plasma Zn (-15% at 8 h, -41% at 24 h) and early loss of Zn from the liver. The Zn changes seen in MT-null mice were largely attributable to LPS-associated anorexia. Food deprivation (20 h) alone caused respective 14% and 30% decreases in hepatic and plasma Zn concentrations and a 27% reduction in total liver Zn reserves, whereas fasted normal mice conserved Zn with a 4-fold increase in hepatic MT. This study confirms that MT synthesis is essential for endotoxin-induced liver Zn accumulation.

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Section: Discussionmentioning

confidence: 99%

Endotoxin-induced inflammation does not cause hepatic zinc accumulation in mice lacking metallothionein gene expression

Philcox

Coyle

Michalska

et al. 1995

Biochemical Journal

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“…As induction of hepatic MT occurs at the onset of inflammation [1][2][3], it has been suggested that the resulting increased supply of exchangeable Zn may facilitate the many enzymic processes necessary for mounting the acute-phase response. Given that glucocorticoids, glucagon, catecholamines and cytokines (interleukin-6 in particular) not only induce MT [9][10][11] and acute-phase protein synthesis [12,13], but also strongly influence hepatic metabolism [11,14,15], the hepatic accumulation of Zn In the absence of any indication of major hepatotoxicity, the results of this study indicate that energy production, and not acute-phase protein synthesis, may be most influenced by Zn supply during endotoxaemia, suggesting that MT has a role in maintaining hepatic and blood glucose in this metabolic setting.…”

Section: Introductionmentioning

confidence: 99%

Trace metal, acute phase and metabolic response to endotoxin in metallothionein-null mice

Rofe

Philcox

Coyle

1996

Biochemical Journal

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Accumulation of hepatic zinc via metallothionein (MT) induction during infection/inflammation is postulated to benefit a range of metabolic processes. The metabolic consequences of two doses of endotoxin (LPS) (1 and 5 mg/kg, intraperitoneally) were examined in normal (MT+/+) and MT-null (MT-/-) mice (all results means =/- S.E.M., n=6). At 16 h after 1 mg/kg LPS, hypozincaemia was pronounced in the MT+/+ mice (4.4+/-0.2 microM), concomitant with a 36% increase in hepatic Zn and a > 10-fold increase in hepatic MT. Plasma Zn (16.6+/-0.7 microM) and total hepatic Zn were unchanged in MT -/- mice, confirming the importance of MT in altering plasma and hepatic Zn during inflammation. Plasma iron was lower in LPS-treated MT-/- mice, whereas plasma copper increased to a similar extent in both groups of mice. Plasma fibrinogen more than doubled, and was similar in both groups of mice, which questions the importance of MT in acute-phase protein synthesis. Blood and liver glucose concentrations were not significantly different between groups before or after LPS, whereas blood and liver lactate concentrations were significantly lower (31% and 24% respectively) in MT-/- mice after LPS. At 16 h after 5 mg/kg LPS, plasma Zn was decreased even further in MT+/+ mice (2.6+/-0.3 microM), but remained unchanged in MT-/- mice at concentrations significantly above those in 16-h fasted MT-/- mice (15.8+/-0.5 versus 11.3+/-0.3 microM). Total liver Zn was 17% lower than fasting values in MT-/- mice, in contrast with 32% higher in MT+/+ mice. Synthesis of MT (in MT+/+ mice) and fibrinogen in all mice was not further enhanced by the higher LPS dose. Blood glucose was significantly decreased by 18% in MT+/+ mice and by 38% in MT-/- mice after 5 mg/kg LPS. There was a marked 44% decrease in liver glucose in MT-/- mice; that in MT+/+ mice was unchanged from fasting levels, implying a deficit in hepatic gluconeogenesis in LPS-treated MT-/- mice. In the absence of any indication of major hepatotoxicity, the results of this study indicate that energy production, and not acute-phase protein synthesis, may be most influenced by Zn supply during endotoxaemia, suggesting that MT has a role in maintaining hepatic and blood glucose in this metabolic setting.

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Einfluß eines Aktivators der Proteinkinase C (TPA) und eines Ca2+-mobilisierenden Agonisten (A 23187) auf den Zinkmetabolismus der Ratte

et al. 1992

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The influence of 12-O-Tetradecanoylphorbol-13-acetate, an activator of proteinkinase C and A 23187, a calcium ionophore increasing cytosolic free calcium concentration on zinc metabolism was investigated in a study with 24 eight-week old rats. Twenty-four hours before killing, the rats (235 g body weight, 8 per group) were either injected intraperitoneally with TPA (1.6 x 10(-7) mol/kg body weight) or A 23187 (1.6 x 10(-6) mol/kg body weight). Control rats received the solvent dimethylsulfoxide. The application of TPA and A 23187 provoked a marked decline in feed intake accompanied by a reduction in body weight and liver mass. Serum concentrations of zinc were reduced significantly after A 23187 injections. TPA and A 23187 increased liver zinc levels by 20 and 30% respectively, if based on fresh and dry weight. The injections, however, did not alter total liver zinc. Liver metallothionein (MT) concentration was elevated 2.4-fold after TPA administration. The increase in response to A 23187 was only 1.5-fold and not significant. Mucosa MT levels were not altered. Serum activity of alkaline phosphatase was significantly reduced (TPA: -23%, A 23187: -31%). There was no change in serum glucose after injections. However, serum creatinine and urea were increased in response to A 23187. In conclusion, TPA and A 23187 had an effect on zinc metabolism of the rat, most marked in the case of MT induction in the liver. There is evidence that the reduced feed intake caused by TPA and A 23187 resulted in effects indistinguishable from those caused by fasting. Further experiments are needed to clarify whether proteinkinase C and cytosolic free calcium are directly involved in the regulation of zinc metabolism.

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The Involvement of Catecholamines and Polypeptide Hormones in the Multihormonal Modulation of Rat Hepatic Zinc Thionein Levels

Cited by 10 publications

References 17 publications

Endotoxin-induced inflammation does not cause hepatic zinc accumulation in mice lacking metallothionein gene expression

Endotoxin-induced inflammation does not cause hepatic zinc accumulation in mice lacking metallothionein gene expression

Trace metal, acute phase and metabolic response to endotoxin in metallothionein-null mice

Einfluß eines Aktivators der Proteinkinase C (TPA) und eines Ca2+-mobilisierenden Agonisten (A 23187) auf den Zinkmetabolismus der Ratte

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