Copper and zinc distribution in the human retina: Relationship to cadmium accumulation, age, and gender

Wills, N. K.; Ramanujam, V. M. Sadagopa; Kalariya, Nilesh; Lewis, J.R.; Kuijk, Frederik J.G.M. van

doi:10.1016/j.exer.2008.04.013

Cited by 70 publications

(63 citation statements)

References 19 publications

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“…This is regularly observed in a variety of conditions, e.g. (Nakazato et al 2008;Wills et al 2008;Kippler et al 2009). A survey of the relevance of metal homeostasis to cadmium toxicity follows.…”

Section: Replacement Of Biological Metals By Cadmiummentioning

confidence: 99%

Cellular mechanisms of cadmium toxicity related to the homeostasis of essential metals

2010

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The widespread occurrence of cadmium in the environment continues to pose a threat to human health despite attempts at limiting its technological uses. The biologically significant ionic form of cadmium, Cd(2+), binds to many bio-molecules and these interactions underlie the toxicity mechanisms of cadmium. Some of the molecules specialized in the handling of alkaline earth (Mg(2+), Ca(2+)) and transition metal ions (e.g. Zn(2+), Cu(2+/+), Fe(3+/2+)) should be particularly sensitive to the presence of Cd(2+), because they enclose cationic sites to which the toxic metal can bind. The possible molecular targets of this kind for cadmium are considered herein. Whereas in vitro evidence for native cation replacement by Cd(2+) in bio-molecules has been largely provided, the demonstration of such occurrences in vivo is scarce, with the notable exception of metallothionein. One reason might be that realistic low-level Cd(2+) contaminations involve cellular concentrations far smaller than those of endogenous cations that usually saturate their binding sites. It is very likely that cadmium toxicity is most often mediated by biological systems amplifying the signals triggered by the presence of Cd(2+). The interference of Cd(2+) with redox sensitive systems acting at the transcriptional and post-transcriptional levels is instrumental in such processes. A better understanding of cadmium toxicity to tackle the environmental challenges lying ahead thus requires properly designed studies implementing biologically relevant cadmium concentrations on different cell types, improved knowledge of the homeostasis of essential metals, and use of these data in a theoretical framework integrating all cellular aspects of cadmium effects.

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Section: Replacement Of Biological Metals By Cadmiummentioning

confidence: 99%

Cellular mechanisms of cadmium toxicity related to the homeostasis of essential metals

2010

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“…28 Zinc levels decline with age in the neural retina and increase with age in the choroid. High concentrations of zinc are found in sub-RPE deposits, particularly in eyes with AMD.…”

Section: Zinc Deficiency and Retinal Physiologic Manifestationsmentioning

confidence: 99%

Zinc Deficiency and the Eye

Nicholson

Prasad

Chew

2014

Handbook of Nutrition, Diet and the Eye

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“…Similar levels of cadmium accumulation in liver and pancreas may indicate similarity in cadmium uptake rates in these two organs. Erie et al (2005) and Wills et al (2008) found that RPE and choroids from human eyes contained more cadmium than did the retina. In addition they noted that females, old age and smokers had elevated levels of cadmium accumulation in eye tissues.…”

Section: How Much Cadmium Is Accumulated In Human Body?mentioning

confidence: 99%

“…In addition they noted that females, old age and smokers had elevated levels of cadmium accumulation in eye tissues. Accumulation of cadmium in RPE has been linked to the development of age-related macular degeneration (Erie et al 2005(Erie et al , 2007Wills et al 2008Wills et al , 2009). …”

Section: How Much Cadmium Is Accumulated In Human Body?mentioning

confidence: 99%

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Emerging Roles of Cadmium and Heme Oxygenase in Type-2 Diabetes and Cancer Susceptibility

Satarug

2012

Tohoku J. Exp. Med.

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Many decades after an outbreak of severe cadmium poisoning, known as Itai-itai disease, cadmium continues to pose a significant threat to human health worldwide. This review provides an update on the effects of this environmental toxicant cadmium, observed in numerous populations despite modest exposure levels. In addition, it describes the current knowledge on the link between heme catabolism and glycolysis. It examines novel functions of heme oxygenase-2 (HO-2) that protect against type 2-diabetes and obesity, which have emerged from diabetic/obese phenotypes of the HO-2 knockout mouse model. Increased cancer susceptibility in type-2 diabetes has been noted in several large cohorts. This is a cause for concern, given the high prevalence of type-2 diabetes worldwide. A lifetime exposure to cadmium is associated with pre-diabetes, diabetes, and overall cancer mortality with sex-related differences in specific types of cancer. Liver and kidney are target organs for the toxic effects of cadmium. These two organs are central to the maintenance of blood glucose levels. Further, inhibition of gluconeogenesis is a known effect of heme, while cadmium has the propensity to alter heme catabolism. This raises the possibility that cadmium may mimic certain HO-2 deficiency conditions, resulting in diabetic symptoms. Intriguingly, evidence has emerged from a recent study to suggest the potential interaction and co-regulation of HO-2 with the key regulator of glycolysis: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4). HO-2 could thus be critical to a metabolic switch to cancer-prone cells because the enzyme PFKFB and glycolysis are metabolic requirements for cell proliferation and resistance to apoptosis.

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Copper and zinc distribution in the human retina: Relationship to cadmium accumulation, age, and gender

Cited by 70 publications

References 19 publications

Cellular mechanisms of cadmium toxicity related to the homeostasis of essential metals

Cellular mechanisms of cadmium toxicity related to the homeostasis of essential metals

Zinc Deficiency and the Eye

Emerging Roles of Cadmium and Heme Oxygenase in Type-2 Diabetes and Cancer Susceptibility

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