Methylmercury and H2O2 provoke lysosomal damage in human astrocytoma D384 cells followed by apoptosis

Daré, Elisabetta; Li, Wei; Zhivotovsky, Boris; Yuan, Xi; Ceccatelli, Sandra

doi:10.1016/s0891-5849(01)00526-3

Cited by 68 publications

(50 citation statements)

References 44 publications

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“…44 In H 2 O 2 -induced apoptosis, lysosome disruption occurred quickly 44 and preceded cytochrome c release and loss of DC m . 45 A recent study by Nilsson et al 46 is particularly germane to the questions raised above. Specifically, these investigators demonstrated that lysosomal membranes are very susceptible to damage and disruption by a variety of oxidants.…”

Section: Discussionmentioning

confidence: 98%

“…32,42,43 Two groups have also reported that H 2 O 2 causes lysosome disruption and the induction of apoptosis, necrosis, or both. 44,45 The mode of death appears to be dependent upon the concentration of H 2 O 2 used to treat the cells. 44 In H 2 O 2 -induced apoptosis, lysosome disruption occurred quickly 44 and preceded cytochrome c release and loss of DC m .…”

Section: Discussionmentioning

confidence: 99%

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Release of cytochrome c and activation of pro-caspase-9 following lysosomal photodamage involves bid cleavage

et al. 2002

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Photodynamic therapy (PDT) protocols employing lysosomal sensitizers induce apoptosis via a mechanism that causes cytochrome c release prior to loss of mitochondrial membrane potential (DC m ). The current study was designed to determine how lysosomal photodamage initiates mitochondrialmediated apoptosis in murine hepatoma 1c1c7 cells. Fluorescence microscopy demonstrated that the photosensitizer N-aspartyl chlorin e6 (NPe6) localized to the lysosomes. Irradiation of cultures preloaded with NPe6 induced the rapid destruction of lysosomes, and subsequent cleavage/activation of Bid, pro-caspases-9 and -3. Pro-caspase-8 was not activated. Release of cytochrome c occurred at about the time of Bid cleavage and preceded the loss of DC m . Extracts of purified lysosomes catalyzed the in vitro cleavage of cytosolic Bid, but not pro-caspase-3 activation. Pharmacological inhibition of cathepsin B, L and D activities did not suppress Bid cleavage or pro-caspases-9 and -3 activation. These studies demonstrate that photodamaged lysosomes trigger the mitochondrial apoptotic pathway by releasing proteases that activate Bid.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Release of cytochrome c and activation of pro-caspase-9 following lysosomal photodamage involves bid cleavage

et al. 2002

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“…The generation of intralysosomal free radicals may cause peroxidation of membrane polyunsaturated fatty acids to form relatively stable and cytotoxic aldehydes, alkenals, or hydroxyalkenals, including malondialdehyde or 4-hydroxy-nonenal (4-HNE) (50). Treatment of purified protein with 4-HNE, for instance, has been shown not only to form protein cross-links (36,54,156) and generate proteinassociated fluorescence similar to that found in the autofluorescent lipofuscin (55,63,152), but also to cause enzyme inactivation (30,38,50,134,144,156) that may further enhance lipofuscin accumulation.…”

Section: Figmentioning

confidence: 99%

Oxidative Stress and Autophagy in the Regulation of Lysosome-Dependent Neuron Death

Pivtoraiko

Stone

Roth

et al. 2009

Antioxidants & Redox Signaling

108

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Lysosomes critically regulate the pH-dependent catabolism of extracellular and intracellular macromolecules delivered from the endocytic/heterophagy and autophagy pathways, respectively. The importance of lysosomes to cell survival is underscored not only by their unique ability effectively to degrade metalloproteins and oxidatively damaged macromolecules, but also by the distinct potential for induction of both caspase-dependent and -independent cell death with a compromise in the integrity of lysosome function. Oxidative stress and free radical damage play a principal role in cell death induced by lysosome dysfunction and may be linked to several upstream and downstream stimuli, including alterations in the autophagy degradation pathway, inhibition of lysosome enzyme function, and lysosome membrane damage. Neurons are sensitive to lysosome dysfunction, and the contribution of oxidative stress and free radical damage to lysosome dysfunction may contribute to the etiology of neurodegenerative disease. This review provides a broad overview of lysosome function and explores the contribution of oxidative stress and autophagy to lysosome dysfunction-induced neuron death. Putative signaling pathways that either induce lysosome dysfunction or result from lysosome dysfunction or both, and the role of oxidative stress, free radical damage, and lysosome dysfunction in pediatric lysosomal storage disorders (neuronal ceroid lipofuscinoses or NCL/Batten disease) and in Alzheimer's disease are emphasized. Antioxid. Redox Signal. 11,[481][482][483][484][485][486][487][488][489][490][491][492][493][494][495][496]

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“…Lysosomal destabilization has been recognized as a feature of oxidative stress-induced cell damage (Zdolsek et al, 1993), and ROS can induce lysosomal leakage, possibly as a consequence of intralysosomal iron-catalysed oxidative processes (Antunes et al, 2001;Dare et al, 2001;Persson et al, 2003). Many apoptotic stimuli that induce lysosomal permeabilization, such as TNF-a (Manna et al, 1998) and lipopolysaccharide (Wang et al, 1997), as well as lightactivated photosensitizing lysosomotropic agents (Ferri and Kroemer, 2001b), also induce generation of intracellular H 2 O 2 during apoptosis.…”

Section: Mechanisms Of Lysosomal Permeabilizationmentioning

confidence: 99%

Lysosomes in cell death

2004

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For many years apoptosis research has focused on caspases and their putative role as sole executioners of programmed cell death. Accumulating information now suggests that lysosomal cathepsins are also pivotally involved in this process, especially in pathological conditions. In particular, the role of lysosomes and lysosomal enzymes in initiation and execution of the apoptotic program has become clear in several models, to the point that the existence of a 'lysosomal pathway of apoptosis' is now generally accepted. This pathway of apoptosis can be activated by death receptors, lipid mediators, and photodamage. Lysosomal proteases can be released from the lysosomes into the cytosol, where they contribute to the apoptotic cascade upstream of mitochondria. This review focuses on the players and the molecular mechanisms involved in the lysosomal pathway of apoptosis as well as on the importance of this pathway in development and pathology.

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Methylmercury and H2O2 provoke lysosomal damage in human astrocytoma D384 cells followed by apoptosis

Cited by 68 publications

References 44 publications

Release of cytochrome c and activation of pro-caspase-9 following lysosomal photodamage involves bid cleavage

Release of cytochrome c and activation of pro-caspase-9 following lysosomal photodamage involves bid cleavage

Oxidative Stress and Autophagy in the Regulation of Lysosome-Dependent Neuron Death

Lysosomes in cell death

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