Online citations, reference lists, and bibliographies.
← Back to Search

Apoptosis Induced By Exposure To A Low Steady-state Concentration Of H2O2 Is A Consequence Of Lysosomal Rupture

F. Antunes, E. Cadenas, U. Brunk
Published 2001 · Biology

Save to my Library
Download PDF
Analyze on Scholarcy Visualize in Litmaps
Share
Reduce the time it takes to create your bibliography by a factor of 10 by using the world’s favourite reference manager
Time to take this seriously.
Get Citationsy
We have re-examined the lysosomal hypothesis of oxidative-stress-induced apoptosis using a new technique for exposing cells in culture to a low steady-state concentration of H 2 O 2 . This steady-state technique mimics the situation in vivo better than the bolus-administration method. A key aspect of H 2 O 2 -induced apoptosis is that the apoptosis is evident only after several hours, although cells may become committed within a few minutes of exposure to this particular reactive oxygen species. In the present work, we were able to show, for the first time, several correlative links between the triggering effect of H 2 O 2 and the later onset of apoptosis: (i) a short (15min) exposure to H 2 O 2 caused almost immediate, albeit limited, lysosomal rupture; (ii) early lysosomal damage, and later apoptosis, showed a similar dose-related response to H 2 O 2 ; (iii) both events were inhibited by pre-treatment with iron chelators, including desferrioxamine. This compound is known to be taken up by endocytosis only and thus to become localized in the lysosomal compartment. After exposure to oxidative stress, when cells were again in standard culture conditions, a time-dependent continuous increase in lysosomal rupture was observed, resulting in a considerably lowered number of intact lysosomes in apoptotic cells, whereas non-apoptotic cells from the same batch of oxidative-stress-exposed cells showed mainly intact lysosomes. Taken together, our results reinforce earlier findings and strongly suggest that lysosomal rupture is an early upstream initiating event, and a consequence of intralysosomal iron-catalysed oxidative processes, when apoptosis is induced by oxidative stress.



This paper is referenced by
10.1039/d0an00824a
A highly specific probe for the imaging of inflammation-induced endogenous nitric oxide produced during the stroke process.
Chenchen Li (2020)
10.2147/JIR.S280419
Human Lung Macrophages Challenged to Oxidants ex vivo: Lysosomal Membrane Sensitization is Associated with Inflammation and Chronic Airflow Limitation
H. L. Persson (2020)
10.1016/j.nano.2018.11.013
Genotoxicity of amorphous silica nanoparticles: Status and prospects.
M. Yazdimamaghani (2019)
10.3892/etm.2018.6187
Changes of lysosomal membrane permeabilization and lipid metabolism in sidt2 deficient mice
Yu Meng (2018)
10.1016/j.biomaterials.2017.10.044
Biological safety and tissue distribution of (16-mercaptohexadecyl)trimethylammonium bromide-modified cationic gold nanorods.
M. Zarska (2018)
10.1016/j.jtemb.2017.01.005
The role of the iron catalyst in the toxicity of multi-walled carbon nanotubes (MWCNTs).
G. Visalli (2017)
10.1016/j.redox.2017.04.039
Quantitative biology of hydrogen peroxide signaling
F. Antunes (2017)
10.1111/aos.13076
Attenuation of iron‐binding proteins in ARPE‐19 cells reduces their resistance to oxidative stress
Markus Karlsson (2016)
10.1104/pp.16.00840
Chronic Iron Limitation Confers Transient Resistance to Oxidative Stress in Marine Diatoms1
Shiri Graff van Creveld (2016)
10.1155/2016/6724585
Zinc Chelation Mediates the Lysosomal Disruption without Intracellular ROS Generation
A. C. Matias (2016)
10.1016/j.brainresbull.2015.11.007
Protective mechanisms of CA074-me (other than cathepsin-B inhibition) against programmed necrosis induced by global cerebral ischemia/reperfusion injury in rats
Y. Xu (2016)
10.1016/j.bbamcr.2016.04.017
Lysosomal membrane stability plays a major role in the cytotoxic activity of the anti-proliferative agent, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT).
Elaine Gutierrez (2016)
10.1089/ADT.2016.727
Discovery of Small Molecules That Induce Lysosomal Cell Death in Cancer Cell Lines Using an Image-Based Screening Platform.
Romina J. Pagliero (2016)
10.1155/2016/1245049
Role of ROS and RNS Sources in Physiological and Pathological Conditions
S. Di Meo (2016)
10.1039/C6RA01625A
Europium-doped NaYF4 nanoparticles cause the necrosis of primary mouse bone marrow stromal cells through lysosome damage
K. Ge (2016)
10.1002/9781118978320.CH19
Lysosome Dysfunction: An Emerging Mechanism of Xenobiotic‐Induced Toxicity
S. Lu (2016)
10.1016/j.bbamem.2015.04.008
The Parkinson-associated human P5B-ATPase ATP13A2 protects against the iron-induced cytotoxicity.
D. Rinaldi (2015)
10.1002/ELAN.201400629
High Sensitive Microsensor Based on Organic-Inorganic Composite for Two-Dimensional Mapping of H2O2 by SECM
Danielle Diniz Justino (2015)
10.1007/s12035-015-9207-1
The Role of Oxidized Cholesterol in Diabetes-Induced Lysosomal Dysfunction in the Brain
C. Sims-Robinson (2015)
10.1016/j.chemosphere.2014.10.054
The role of lysosomes in BDE 47-mediated activation of mitochondrial apoptotic pathway in HepG2 cells.
X. Liu (2015)
10.3109/10428194.2014.955022
Molecular damage caused by generation of reactive oxygen species in the redox cycle of doxorubicin–transferrin conjugate in human leukemia cell lines
Marzena Szwed (2015)
10.1016/J.CARBON.2015.07.057
Size-tailored synthesis of gold nanoparticles and their facile deposition on AAO-templated carbon nanotubes via electrostatic self-assembly: Application to H2O2 detection
Panvika Pannopard (2015)
10.1007/s10495-014-0985-0
WIN induces apoptotic cell death in human colon cancer cells through a block of autophagic flux dependent on PPARγ down-regulation
O. Pellerito (2014)
10.1007/978-1-4614-9545-1_6
Modulating Autophagy and the “Reverse Warburg Effect”
M. Vaccaro (2014)
10.1038/onc.2013.314
Stefin B deficiency reduces tumor growth via sensitization of tumor cells to oxidative stress in a breast cancer model
M. Butinar (2014)
10.12717/DEVREP.2014.18.4.225
Biphasic activity of chloroquine in human colorectal cancer cells.
Deok-bae Park (2014)
10.3390/molecules19043988
Camalexin-Induced Apoptosis in Prostate Cancer Cells Involves Alterations of Expression and Activity of Lysosomal Protease Cathepsin D
B. Smith (2014)
10.1039/C4TB00056K
Calcium phosphate nanoparticles primarily induce cell necrosis through lysosomal rupture: the origination of material cytotoxicity.
Zhaoming Liu (2014)
10.1007/s10495-014-1005-0
Campylobacter jejuni cell lysates differently target mitochondria and lysosomes on HeLa cells
B. Canonico (2014)
10.1016/J.SNB.2014.01.043
A simple non-enzymatic hydrogen peroxide sensor using gold nanoparticles-graphene-chitosan modified electrode
Ningming Jia (2014)
10.1016/j.taap.2014.07.022
Lysosomal membrane permeabilization: carbon nanohorn-induced reactive oxygen species generation and toxicity by this neglected mechanism.
Mei Yang (2014)
10.1038/nchembio.1416
The role of iron and reactive oxygen species in cell death.
S. Dixon (2014)
See more
Semantic Scholar Logo Some data provided by SemanticScholar