Induction of cell death by the lysosomotropic detergent MSDH

Li, Wei; Yuan, Xi; Nordgren, Gunnar; Dalen, Helge; Dubowchik, Gene M.; Firestone, Raymond A.; Brunk, Ulf T.

doi:10.1016/s0014-5793(00)01286-2

Cited by 223 publications

(216 citation statements)

References 26 publications

Supporting

Mentioning

210

Contrasting

Order By: Relevance

“…3). Dependent on the magnitude of lysosomal rupture, cell proliferation is stimulated or arrested by a minor or a somewhat more pronounced lysosomal destabilization, respectively, while apoptosis or necrosis have been found to follow moderate or major destabilization, respectively (Li et al, 2000, Terman et al, 2010. Consequently, the amelioration of LMP by chelating lysosomal redox-active iron in a non-redox-active form ought to reduce radiation sensitivity.…”

Section: Lysosomal Iron and Ionizing Irradiationmentioning

confidence: 99%

The role of lysosomes in iron metabolism and recycling

Kurz

Eaton

Brunk

2011

The International Journal of Biochemistry & Cell Biology

Self Cite

167

134

View full text Add to dashboard Cite

Iron is the most abundant transition metal in the earths crust. It cycles easily between ferric (oxidized; Fe(III)) and ferrous (reduced; Fe(II)) and readily forms complexes with oxygen, making this metal a central player in respiration and related redox processes. However, loose iron, not within heme or iron-sulfur cluster proteins, can be destructively redox-active, causing damage to almost all cellular components, killing both cells and organisms. This may explain why iron is so carefully handled by aerobic organisms. Iron uptake from the environment is carefully limited and carried out by specialized iron transport mechanisms. One reason that iron uptake is tightly controlled is that most organisms and cells cannot efficiently excrete excess iron. When even small amounts of intracellular free iron occur, most of it is safely stored in a non-redox-active form in ferritins. Within nucleated cells, iron is constantly being recycled from aged iron-rich organelles such as mitochondria and used for construction of new organelles. Much of this recycling occurs within the lysosome, an acidic digestive organelle. Because of this, most lysosomes contain relatively large amounts of redox-active iron and are therefore unusually susceptible to oxidant-mediated destabilization or rupture. In many cell types, iron transit through the lysosomal compartment can be remarkably brisk. However, conditions adversely affecting lysosomal iron handling (or oxidant stress) can contribute to a variety of acute and chronic diseases. These considerations make normal and abnormal lysosomal handling of iron central to the understanding and, perhaps, therapy of a wide range of diseases

show abstract

Section: Lysosomal Iron and Ionizing Irradiationmentioning

confidence: 99%

The role of lysosomes in iron metabolism and recycling

Kurz

Eaton

Brunk

2011

The International Journal of Biochemistry & Cell Biology

Self Cite

167

134

View full text Add to dashboard Cite

show abstract

“…4 Severe oxidative stress has also been associated with LMP and consequent necrosis. 10 Extracellular application of 0.01-1 mM peroxide is physiologically relevant and broadly mimics the release of endogenous H 2 O 2 . 11 For example, activated neutrophils generate up to 6 Â 10 À14 mol H 2 O 2 /h per cell, generating a local concentration of 10-100 mM H 2 O 2 .…”

mentioning

confidence: 99%

Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features

et al. 2009

View full text Add to dashboard Cite

Necroptosis, necrosis and secondary necrosis following apoptosis represent different modes of cell death that eventually result in similar cellular morphology including rounding of the cell, cytoplasmic swelling, rupture of the plasma membrane and spilling of the intracellular content. Subcellular events during tumor necrosis factor (TNF)-induced necroptosis, H2O2-induced necrosis and anti-Fas-induced secondary necrosis were studied using high-resolution time-lapse microscopy. The cellular disintegration phase of the three types of necrosis is characterized by an identical sequence of subcellular events, including oxidative burst, mitochondrial membrane hyperpolarization, lysosomal membrane permeabilization and plasma membrane permeabilization, although with different kinetics. H2O2-induced necrosis starts immediately by lysosomal permeabilization. In contrast, during TNF-mediated necroptosis and anti-Fas-induced secondary necrosis, this is a late event preceded by a defined signaling phase. TNF-induced necroptosis depends on receptor-interacting protein-1 kinase, mitochondrial complex I and cytosolic phospholipase A(2) activities, whereas H2O2-induced necrosis requires iron-dependent Fenton reactions

show abstract

“…The higher levels in plasma and lower activities in lysosomal fractions of these enzymes, as observed in the present study, may be due either to the infiltration of inflammatory cells or due to isoprenaline-mediated lysosomal fragility by Ca 2+ overload. A necrotic cell death can be triggered by a too strong lysosomal membrane permeabilization (Li et al 2000) and oxygen free radicals are primarily responsible for the release of lysosomal hydrolases. It has also been suggested that abnormal release and activation of lysosomal enzymes during ischemia and other potentially lethal events may contribute to the tissue damage.…”

Section: Resultsmentioning

confidence: 99%

Protective effect of betaine on changes in the levels of lysosomal enzyme activities in heart tissue in isoprenaline-induced myocardial infarction in Wistar rats

Ganesan

Anandan

2009

Cell Stress and Chaperones

View full text Add to dashboard Cite

Myocardial infarction is one of the most common manifestations of cardiovascular disease. In the present study, we investigated the protective effect of betaine, a potent lipotropic molecule, on changes in the levels of lysosomal enzymes and lipid peroxidation in isoprenalineinduced myocardial infarction in Wistar rats, an animal model of myocardial infarction in man. Male albino Wistar rats were pretreated with betaine (250 mg/kg body weight) daily for a period of 30 days. After the treatment period, isoprenaline (11 mg/100 g body weight) was intraperitoneally administered to rats at intervals of 24 h for 2 days. The activities of lysosomal enzymes (β-glucuronidase, β-galactosidase, β-glucosidase, and acid phosphatase) were significantly (p<0.05) increased in plasma with a concomitant decline in the activities of these enzymes in heart tissue of isoprenaline-administered rats. Also, the level of lipid peroxidation was higher in heart lysosomes of isoprenaline-injected rats. Pretreatment with betaine daily for a period of 30 days to isoprenaline-induced rats prevented the changes in the activities of these lysosomal enzymes. Oral treatment with betaine (250 mg/kg body weight) to normal control rats did not show any significant effect in all the biochemical parameters studied. Thus, the results of our study show that betaine protects the lysosomal membrane against isoprenaline-induced myocardial infarction. The observed effects might be due to the free radical-scavenging and membrane-stabilizing properties of betaine.

show abstract

Induction of cell death by the lysosomotropic detergent MSDH

Cited by 223 publications

References 26 publications

The role of lysosomes in iron metabolism and recycling

The role of lysosomes in iron metabolism and recycling

Necroptosis, necrosis and secondary necrosis converge on similar cellular disintegration features

Protective effect of betaine on changes in the levels of lysosomal enzyme activities in heart tissue in isoprenaline-induced myocardial infarction in Wistar rats

Contact Info

Product

Resources

About