Transition metal homeostasis: from yeast to human disease

Bleackley, Mark R.; MacGillivray, Ross T. A.

doi:10.1007/s10534-011-9451-4

Cited by 204 publications

(185 citation statements)

References 262 publications

Supporting

Mentioning

176

Contrasting

Unclassified

Order By: Relevance

“…A ging and age-associated diseases are becoming the fastestgrowing area of epidemiology in most developed countries (1)(2)(3)(4). Identification of molecular mechanisms that lead to the development of interventions to delay the onset of age-associated diseases could have tremendous global impacts on public health (5).…”

Section: Saccharomyces Cerevisiaementioning

confidence: 99%

High-throughput analysis of yeast replicative aging using a microfluidic system

Liu

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

150

176

View full text Add to dashboard Cite

Saccharomyces cerevisiae has been an important model for studying the molecular mechanisms of aging in eukaryotic cells. However, the laborious and low-throughput methods of current yeast replicative lifespan assays limit their usefulness as a broad genetic screening platform for research on aging. We address this limitation by developing an efficient, high-throughput microfluidic single-cell analysis chip in combination with high-resolution time-lapse microscopy. This innovative design enables, to our knowledge for the first time, the determination of the yeast replicative lifespan in a highthroughput manner. Morphological and phenotypical changes during aging can also be monitored automatically with a much higher throughput than previous microfluidic designs. We demonstrate highly efficient trapping and retention of mother cells, determination of the replicative lifespan, and tracking of yeast cells throughout their entire lifespan. Using the high-resolution and large-scale data generated from the high-throughput yeast aging analysis (HYAA) chips, we investigated particular longevity-related changes in cell morphology and characteristics, including critical cell size, terminal morphology, and protein subcellular localization. In addition, because of the significantly improved retention rate of yeast mother cell, the HYAA-Chip was capable of demonstrating replicative lifespan extension by calorie restriction.microfluidics | high-throughput | replicative aging | calorie restriction | Saccharomyces cerevisiae

show abstract

Section: Saccharomyces Cerevisiaementioning

confidence: 99%

High-throughput analysis of yeast replicative aging using a microfluidic system

Liu

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

150

176

View full text Add to dashboard Cite

show abstract

“…Mn, Fe, Co, Ni, Cu and Zn) incorporated into protein structures [1][2][3]. Metalloenzymes, such as superoxide dismutase (SOD), catalase (CAT) and peroxidase (PO), represent the first line of defence against reactive oxygen species (ROS) in the cellular environment.…”

Section: Introductionmentioning

confidence: 99%

Cellular Redox State Modifications Induced by Bioactive Fe(III)-Cyclophane Complexes Approaching to Selective Therapy Drug Design

Salazar-Medina¹,

Alday²,

Carreno³

et al. 2017

Med chem

View full text Add to dashboard Cite

Previously we reported the capacity of the bio-inspired Fe(III) complexes, Fe 2 PO and Fe 2 PC, to mimic the activity of superoxide dismutase and peroxidase enzymes, as well as their capacity to reduce the cytotoxicity generated by superoxide radicals in human peripheral blood mononuclear cells, under stress conditions. Based on those findings, we decided to evaluate the cytotoxicity, antioxidant and redox state modulation capacity of Fe 2 PO and Fe 2 PC complexes, pondering them as drug candidates against free radicals unbalance disorders. Fe 2 PO and Fe 2 PC deactivated the ABTS synthetic radical with an IC 50 value of 38.4 ± 0.9 µM and 28.9 ± 0.2 µM, respectively, while against the DPPH radical, the IC 50 value was over the higher concentration tested (>200 µM) for both complexes. As desirable for any drug candidate, none of the metallic complexes (at 25, 50 and 100 µM) induced cytotoxicity on M12.C3.F6 cells (a murine B-cell lymphoma model), but differences in the redox state modulation were observed on the basis of fluorescence detection of a 2′,7′-dichlorofluorescin probe by flow cytometry. Cells under normal conditions and preincubated with Fe 2 PO and Fe 2 PC complexes slightly augmented the reactive oxygen species concentration, meanwhile, cells under stress condition preincubated with H 2 O 2 and metallic complexes, showed a higher augmentation in the reactive oxygen species concentration, in comparison to the controls. Finally, a cellular internalisation assay was performed, showing that Fe 2 PO and Fe 2 PC exert those effects from the outside of the cells. All these results suggest the ability of Fe 2 PO and Fe 2 PC complexes to selectively increase the reactive oxygen species concentration in cells with a free radical unbalance, without inducing mortality in cells under normal conditions.

show abstract

“…Consequently, this element plays an important role in a multitude of physiological processes. Examples of zinc proteins are as follows: metalloproteases, carboxypeptidases and zinc finger proteins, which include DNA-or RNA-binding proteins (Bleackley and MacGillivray 2011). Zinc has also been shown to act as a signalling molecule as Ca (Yamasaki et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Impact of multi-metals (Cd, Pb and Zn) exposure on the physiology of the yeast Pichia kudriavzevii

Mesquita

Machado

Silva

et al. 2015

Environ Sci Pollut Res

View full text Add to dashboard Cite

Metal contamination of the environment is frequently associated to the presence of two or more metals. This work aimed to study the impact of a mixture of metals (Cd, Pb and Zn) on the physiology of the non-conventional yeast Pichia kudriavzevii. The incubation of yeast cells with 5 mg/ l Cd, 10 mg/l Pb and 5 mg/l Zn, for 6 h, induced a loss of metabolic activity (assessed by FUN-1 staining) and proliferation capacity (evaluated by a clonogenic assay), with a small loss of membrane integrity (measured by trypan blue exclusion assay). The staining of yeast cells with calcofluor white revealed that no modification of chitin deposition pattern occurred during the exposure to metal mixture. Extending for 24 h, the exposure of yeast cells to metal mixture provoked a loss of membrane integrity, which was accompanied by the leakage of intracellular components. A marked loss of the metabolic activity and the loss of proliferation capacity were also observed. The analysis of the impact of a single metal has shown that, under the conditions studied, Pb was the metal responsible for the toxic effect observed in the metal mixture. Intracellular accumulation of Pb seems to be correlated with the metals' toxic effects observed.

show abstract

Transition metal homeostasis: from yeast to human disease

Cited by 204 publications

References 262 publications

High-throughput analysis of yeast replicative aging using a microfluidic system

High-throughput analysis of yeast replicative aging using a microfluidic system

Cellular Redox State Modifications Induced by Bioactive Fe(III)-Cyclophane Complexes Approaching to Selective Therapy Drug Design

Impact of multi-metals (Cd, Pb and Zn) exposure on the physiology of the yeast Pichia kudriavzevii

Contact Info

Product

Resources

About