β‐Carotene cleavage products induce oxidative stress<i>in vitro</i>by impairing mitochondrial respiration

Siems, Werner; Sommerburg, Olaf; Schild, Lorenz; Augustin, Wolfgang; Langhans, Claus-Dieter; Wiswedel, Ingrid

doi:10.1096/fj.01-0765fje

Cited by 111 publications

(80 citation statements)

References 55 publications

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“…Related to our study, previous work showed that carotenoid cleavage products, such as highly reactive aldehydes and epoxides, cause oxidative stress by impairing mitochondrial function (52). Evidence is presented here that one mechanism of cell death induced by all-transretinal involves an intrinsic apoptotic pathway associated with mitochondrial impairment due to a rapid increase of intracellular calcium concentration (Figs.…”

Section: Abca4supporting

confidence: 77%

Involvement of All-trans-retinal in Acute Light-induced Retinopathy of Mice

Maeda¹,

Maeda²,

Golczak³

et al. 2009

Journal of Biological Chemistry

220

307

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Exposure to bright light can cause visual dysfunction and retinal photoreceptor damage in humans and experimental animals, but the mechanism(s) remain unclear. We investigated whether the retinoid cycle (i.e. the series of biochemical reactions required for vision through continuous generation of 11-cis-retinal and clearance of all-trans-retinal, respectively) might be involved. Previously, we reported that mice lacking two enzymes responsible for clearing all-trans-retinal, namely photoreceptor-specific ABCA4 (ATP-binding cassette transporter 4) and RDH8 (retinol dehydrogenase 8), manifested retinal abnormalities exacerbated by light and associated with accumulation of diretinoid-pyridinium-ethanolamine (A2E), a condensation product of all-trans-retinal and a surrogate marker for toxic retinoids. Now we show that these mice develop an acute, light-induced retinopathy. However, cross-breeding these animals with lecithin:retinol acyltransferase knock-out mice lacking retinoids within the eye produced progeny that did not exhibit such light-induced retinopathy until gavaged with the artificial chromophore, 9-cis-retinal. No significant ocular accumulation of A2E occurred under these conditions. These results indicate that this acute light-induced retinopathy requires the presence of free all-trans-retinal and not, as generally believed, A2E or other retinoid condensation products. Evidence is presented that the mechanism of toxicity may include plasma membrane permeability and mitochondrial poisoning that lead to caspase activation and mitochondria-associated cell death. These findings further understanding of the mechanisms involved in light-induced retinal degeneration.

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Section: Abca4supporting

confidence: 77%

Involvement of All-trans-retinal in Acute Light-induced Retinopathy of Mice

Maeda¹,

Maeda²,

Golczak³

et al. 2009

Journal of Biological Chemistry

220

307

View full text Add to dashboard Cite

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“…Being electrophilic, the α,β-unsaturated carbonyl group of β-CC and β-I can react with electron donors such as, for example, sulphydryl groups in proteins (15,16). Because of their reactivity, RES can be cytotoxic and, accordingly, a number of previous studies have reported the deleterious effect of high concentrations of β-carotene oxidation products, including β-I, on mitochondrial and chloroplastic functions, DNA intactness, and cell viability (25)(26)(27). In addition, low levels of RES, and particularly those produced during lipid peroxidation, have also effects on plant genome (19,28,29).…”

Section: Discussionmentioning

confidence: 99%

Carotenoid oxidation products are stress signals that mediate gene responses to singlet oxygen in plants

Ramel

Birtić

Giniès

et al. 2012

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

607

665

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1 O 2 (singlet oxygen) is a reactive O 2 species produced from triplet excited chlorophylls in the chloroplasts, especially when plants are exposed to excess light energy. Similarly to other active O 2 species, 1 O 2 has a dual effect: It is toxic, causing oxidation of biomolecules, and it can act as a signal molecule that leads to cell death or to acclimation. Carotenoids are considered to be the main 1 O 2 quenchers in chloroplasts, and we show here that light stress induces the oxidation of the carotenoid β-carotene in Arabidopsis plants, leading to the accumulation of different volatile derivatives. One such compound, β-cyclocitral, was found to induce changes in the expression of a large set of genes that have been identified as 1 O 2 responsive genes. In contrast, β-cyclocitral had little effect on the expression of H 2 O 2 gene markers. β-Cyclocitral–induced reprogramming of gene expression was associated with an increased tolerance to photooxidative stress. The results indicate that β-cyclocitral is a stress signal produced in high light that is able to induce defense mechanisms and represents a likely messenger involved in the 1 O 2 signaling pathway in plants.

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“…S3); and (iii) both retinoids and their condensation products are known to produce cellular toxicity and death (12,18,31,64,65). Retinal pathology could also result from mitochondrial dysfunction, because lipophilic unsaturated compounds such as retinoids can also act as electron acceptors that compromise ATP production (66)(67)(68)(69).…”

Section: Discussionmentioning

confidence: 99%

Two-photon microscopy reveals early rod photoreceptor cell damage in light-exposed mutant mice

Maeda

Palczewska

Golczak³

et al. 2014

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

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Atrophic age-related and juvenile macular degeneration are especially devastating due to lack of an effective cure. Two retinal cell types, photoreceptor cells and the adjacent retinal pigmented epithelium (RPE), reportedly display the earliest pathological changes. Abca4 −/− Rdh8 −/− mice, which mimic many features of human retinal degeneration, allowed us to determine the sequence of light-induced events leading to retinal degeneration. Using two-photon microscopy with 3D reconstruction methodology, we observed an initial strong retinoid-derived fluorescence and expansion of Abca4 −/− Rdh8 −/− mouse rod cell outer segments accompanied by macrophage infiltration after brief exposure of the retina to bright light. Additionally, light-dependent fluorescent compounds produced in rod outer segments were not transferred to the RPE of mice genetically defective in RPE phagocytosis. Collectively, these findings suggest that for light-induced retinopathies in mice, rod photoreceptors are the primary site of toxic retinoid accumulation and degeneration, followed by secondary changes in the RPE.

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β‐Carotene cleavage products induce oxidative stressin vitroby impairing mitochondrial respiration

Cited by 111 publications

References 55 publications

Involvement of All-trans-retinal in Acute Light-induced Retinopathy of Mice

Involvement of All-trans-retinal in Acute Light-induced Retinopathy of Mice

Carotenoid oxidation products are stress signals that mediate gene responses to singlet oxygen in plants

Two-photon microscopy reveals early rod photoreceptor cell damage in light-exposed mutant mice

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