Irradiation of GAPDH: a model for environmentally induced protein damage

Voss, Peter; Hajimiragha, Hossein; Engels, Martina; Ruhwiedel, Carsten; Calles, Christian; Schröeder, Peter; Grune, Tilman

doi:10.1515/bc.2007.068

Cited by 21 publications

(15 citation statements)

References 46 publications

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“…Glutathione reductase and glyceraldehyde-3-P dehydrogenase lost their activity completely after a fluence of 1250 kJ m 22 (,1 %). This is consistent with a previous study on glyceraldehyde-3-P dehydrogenase, where a reduction to 10 % of the initial activity was found with an applied UVA fluence of 1000 kJ m 22 (Voss et al, 2007).…”

Section: Enzymes Of the Cytoplasmsupporting

confidence: 93%

The respiratory chain is the cell's Achilles' heel during UVA inactivation in Escherichia coli

et al. 2010

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Solar disinfection (SODIS) is used as an effective and inexpensive tool to improve the microbiological quality of drinking water in developing countries where no other means are available. Solar UVA light is the agent that inactivates bacteria during the treatment. Damage to bacterial membranes plays a crucial role in the inactivation process. This study showed that even slightly irradiated cells (after less than 1 h of simulated sunlight) were strongly affected in their ability to maintain essential parts of their energy metabolism, in particular of the respiratory chain (activities of NADH oxidase, succinate oxidase and lactate oxidase were measured). The cells' potential to generate ATP was also strongly inhibited. Many essential enzymes of carbon metabolism (glucose-6-phosphate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase and malate dehydrogenase) and defence against oxidative stress (catalases and glutathione-disulfide reductase) were reduced in their activity during SODIS. The work suggests that damage to membrane enzymes is a likely cause of membrane dysfunction (loss of membrane potential and increased membrane permeability) during UVA irradiation. In this study, the first targets on the way to cell death were found to be the respiratory chain and F 1 F 0 ATPase.

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Section: Enzymes Of the Cytoplasmsupporting

confidence: 93%

The respiratory chain is the cell's Achilles' heel during UVA inactivation in Escherichia coli

et al. 2010

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“…Since GAPDH, an active site cysteine-containing glycolytic enzyme, has been shown earlier to be a target of cytotoxic oxidative insult including Rose Bengal-dependent photosensitization and UVA-inactivation [20,35], we examined if UVA-induced changes in activity would occur (Fig. 1A).…”

Section: Resultsmentioning

confidence: 99%

UVA causes dual inactivation of cathepsin B and L underlying lysosomal dysfunction in human dermal fibroblasts

Lamore

Wondrak

2013

Journal of Photochemistry and Photobiology B: Biology

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Cutaneous exposure to chronic solar UVA-radiation is a causative factor in photocarcinogenesis and photoaging. Recently, we have identified the thiol-dependent cysteine-protease cathepsin B as a novel UVA-target undergoing photo-oxidative inactivation upstream of autophagic-lysosomal dysfunction in fibroblasts. In this study, we examined UVA effects on a wider range of cathepsins and explored the occurrence of UVA-induced cathepsin inactivation in other cultured skin cell types. In dermal fibroblasts, chronic exposure to non-cytotoxic doses of UVA caused pronounced inactivation of the lysosomal cysteine-proteases cathepsin B and L, effects not observed in primary keratinocytes and occurring only to a minor extent in primary melanocytes. In order to determine if UVA-induced lysosomal impairment requires single or dual inactivation of cathepsin B and/or L, we used a genetic approach (siRNA) to selectively downregulate enzymatic activity of these target cathepsins. Monitoring an established set of protein markers (including LAMP1, LC3-II, and p62) and cell ultrastructural changes detected by electron microscopy, we observed that only dual genetic antagonism (targeting both CTSB and CTSL expression) could mimic UVA-induced autophagic-lysosomal alterations, whereas single knockdown (targeting CTSB or CTSL only) did not display ‘UVA-mimetic’ effects failing to reproduce the UVA-induced phenotype. Taken together, our data demonstrate that chronic UVA inhibits both cathepsin B and L enzymatic activity and that dual inactivation of both enzymes is a causative factor underlying UVA-induced impairment of lysosomal function in dermal fibroblasts.

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“…This result suggests that ferritin-binding at the cell surface is mediated by a receptor which is inactivated by UV treatment. In support of this possibility, it is known that certain proteins can be inactivated by exposure to UV light [96].…”

Section: Discussionmentioning

confidence: 96%

The Hyphal-Associated Adhesin and Invasin Als3 of Candida albicans Mediates Iron Acquisition from Host Ferritin

et al. 2008

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Iron sequestration by host iron-binding proteins is an important mechanism of resistance to microbial infections. Inside oral epithelial cells, iron is stored within ferritin, and is therefore not usually accessible to pathogenic microbes. We observed that the ferritin concentration within oral epithelial cells was directly related to their susceptibility to damage by the human pathogenic fungus, Candida albicans. Thus, we hypothesized that host ferritin is used as an iron source by this organism. We found that C. albicans was able to grow on agar at physiological pH with ferritin as the sole source of iron, while the baker's yeast Saccharomyces cerevisiae could not. A screen of C. albicans mutants lacking components of each of the three known iron acquisition systems revealed that only the reductive pathway is involved in iron utilization from ferritin by this fungus. Additionally, C. albicans hyphae, but not yeast cells, bound ferritin, and this binding was crucial for iron acquisition from ferritin. Transcriptional profiling of wild-type and hyphal-defective C. albicans strains suggested that the C. albicans invasin-like protein Als3 is required for ferritin binding. Hyphae of an Δals3 null mutant had a strongly reduced ability to bind ferritin and these mutant cells grew poorly on agar plates with ferritin as the sole source of iron. Heterologous expression of Als3, but not Als1 or Als5, two closely related members of the Als protein family, allowed S. cerevisiae to bind ferritin. Immunocytochemical localization of ferritin in epithelial cells infected with C. albicans showed ferritin surrounding invading hyphae of the wild-type, but not the Δals3 mutant strain. This mutant was also unable to damage epithelial cells in vitro. Therefore, C. albicans can exploit iron from ferritin via morphology dependent binding through Als3, suggesting that this single protein has multiple virulence attributes.

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Irradiation of GAPDH: a model for environmentally induced protein damage

Cited by 21 publications

References 46 publications

The respiratory chain is the cell's Achilles' heel during UVA inactivation in Escherichia coli

The respiratory chain is the cell's Achilles' heel during UVA inactivation in Escherichia coli

UVA causes dual inactivation of cathepsin B and L underlying lysosomal dysfunction in human dermal fibroblasts

The Hyphal-Associated Adhesin and Invasin Als3 of Candida albicans Mediates Iron Acquisition from Host Ferritin

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