Manganese metabolism in cows and goats

Gibbons, R. A.; Dixon, S. N.; Hallis, K F; Russell, Andrea; Sansom, B. F.; Symonds, H.W.

doi:10.1016/0304-4165(76)90218-x

Cited by 115 publications

(46 citation statements)

References 19 publications

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“…There have been numerous studies to understand better how manganese is distributed, excreted and accumulated in experimental animals. For example, following intravenous administration in cows, Mn(III)-Tf is removed from the plasma quite slowly, with a half-life of $3 h. By contrast, free Mn 2þ in bovine plasma is very rapidly cleared by the liver and excreted in the bile, at a rate that is $30 times faster than that of Mn(III)-Tf (42). Consequently, it may in fact be possible to generate detectable MRI contrast via this administration route.…”

Section: Discussionmentioning

confidence: 88%

Manganese cell labeling of murine hepatocytes using manganese(III)‐transferrin

Sotak

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Koretsky

2008

Contrast Media & Molecular

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Manganese(III)-transferrin [Mn(III)-Tf] was investigated as a way to accomplish manganese-labeling of murine hepatocytes for MRI contrast. It is postulated that Mn(III)-Tf can exploit the same transferrin-receptor-dependent and -independent metabolic pathways used by hepatocytes to transport the iron analog Fe(III)-Tf. More specifically, it was investigated whether manganese delivered by transferrin could give MRI contrast in hepatocytes. Comparison of the T1 and T2 relaxation times of Mn(III)-Tf and Fe(III)-Tf over the same concentration range showed that the r1 relaxivities of the two metalloproteins are the same in vitro, with little contribution from paramagnetic enhancement. The degree of manganese cell labeling following incubation for 2-7 h in 31.5 microm Mn(III)-Tf was comparable to that of hepatocytes incubated in 500 microm Mn2+ for 1 h. The intrinsic manganese tissue relaxivity between Mn(III)-Tf-labeled and Mn2+-labeled cells was found to be the same, consistent with Mn(III) being released from transferrin and reduced to Mn2+. For both treatment regimens, manganese uptake by hepatocytes appeared to saturate in the first 1-2 h of the incubation period and may explain why the efficiency of hepatocyte cell labeling by the two methods appeared to be comparable in spite of the approximately 16-fold difference in effective manganese concentration. Hepatocytes continuously released manganese, as detected by MRI, and this was the same for both Mn2+- and Mn(III)-Tf-labeled cells. Manganese release may be the result of normal hepatocyte function, much in the same way that hepatocytes excrete manganese into the bile in vivo. This approach exploits a biological process-namely receptor binding, endocytosis and endosomal acidification-to initiate the release of an MRI contrast agent, potentially conferring more specificity to the labeling process. The ubiquitous expression of transferrin receptors by eukaryotic cells should make Mn(III)-Tf particularly useful for manganese labeling of a wide variety of cells both in culture and in vivo.

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Section: Discussionmentioning

confidence: 88%

Manganese cell labeling of murine hepatocytes using manganese(III)‐transferrin

Sotak

Sharer

Koretsky

2008

Contrast Media & Molecular

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“…Mn follows a similar pattern although the enzymes responsible for its transport out of the enterocyte and its oxidation before entering the blood stream have not been identified. Trivalent Mn is preferentially bound to transferrin which escapes the first pass elimination in the liver (Gibbons et al 1976;Davidsson et al 1989). Normally, there is little competition between Mn and iron for binding to transferrin as iron only occupies approximately 30% of the binding sites.…”

Section: Structural Properties Of Dmt1 and Its Role In Mn Transportmentioning

confidence: 99%

Are There Common Biochemical and Molecular Mechanisms Controlling Manganism and Parkisonism

Roth

2009

Neuromol Med

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Over the past several decades there has been considerable progress in our basic knowledge as to the mechanisms and factors regulating Mn toxicity. The disorder known as manganism is associated with the preferential accumulation of Mn in the globus pallidus of the basal ganglia which is generally considered to be the major and initial site of injury. Because the area of the CNS comprising the basal ganglia is very complex and dependent on the precise function and balance of several neurotransmitters, it is not surprising that symptoms of manganism often overlap with that of Parkinson's disease. The fact that neurological symptoms and onset of Mn toxicity are quite broad and can vary unpredictably probably reflects specific genetic variance of the physiological and biochemical makeup within the basal ganglia in any individual. Differences in response to Mn overexposure are, thus, likely due to underlying genetic variability which ultimately presents in deviations in both susceptibility as well as the characteristics of the neurological lesions and symptoms expressed. Although chronic exposure to Mn is not the initial causative agent provoking Parkinsonism, there is evidence suggesting that persistent exposure can predispose an individual to acquire dystonic movements associated with Parkinson's disease. As noted in this review, there appears to be common threads between the two disorders, as mutations in the genes, parkin and ATP13A2, associated with early onset of Parkinsonism, may also predispose an individual to develop Mn toxicity. Mutations in both genes appear to effect transport of Mn into the cell. These genetic difference coupled with additional environmental or nutritional factors must also be considered as contributing to the severity and onset of manganism.

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“…It seems likely that submaximal amounts of Mn supplied continuously through gastro-intestinal absorption function differently in tissues from the excess ion given intermittently by injection. The mechanism by which only orally administered Mn induces goiter is not known, but it is reasonable to consider that the presence of Mn transferrin was demonstrated in the plasma of certain species (Foradori et al, 1967, Hancock et al, 1973, Gibbons et al, 1976, and a similar carrier protein may exist in the mouse and facillitate Mn absorption through the digestive tract. The transferrin-bound Mn remains in circulation for longer periods than the free ion (Foradori et al, 1967, Gibbons et al, 1976 and it may release a free form of Mn gradually.…”

Section: Discussionmentioning

confidence: 99%