Reduced cellular redox status induces 4-hydroxynonenal-mediated caspase 3 activation leading to erythrocyte death during chronic arsenic exposure in rats
- Cell Biology and Physiology Division, Indian Institute of Chemical Biology, CSIR, Kolkata (India)
Chronic exposure to arsenic in rats led to gradual accumulation of the toxicant in erythrocytes causing oxidative stress in these cells. 4-Hydroxynonenal (4-HNE), a major aldehyde product of lipid peroxidation, contributed significantly to the cytopathological events observed during oxidative stress in the erythrocytes of exposed rats. 4-HNE triggered death signal cascade that was initiated with the formation of HNE-protein adducts in cytosol. HNE-protein adduct formation resulted in depletion of cytosolic antioxidants followed by increased generation of ROS. Results showed accumulation of hydrogen peroxide (H{sub 2}O{sub 2}) from the early stages of arsenic exposure, while superoxide (O{sub 2}{sup c}entre dot{sup -}) and hydroxyl radical ({sup c}entre dotOH) also contributed to the oxidative stress during longer period of exposure. Suppression of antioxidant system coupled with increased generation of ROS eventually led to activation of caspase 3 during arsenic exposure. Attenuation of HNE-mediated activation of caspase 3 in presence of N-acetylcysteine (NAC) indicated the involvement of GSH in the process. Prevention of HNE-mediated degradation of membrane proteins in presence of Z-DEVD-FMK identified caspase 3 as the principal mediator of HNE-induced cellular damage during arsenic exposure. Degradation of band 3 followed by its aggregation on the red cell surface promoted immunologic recognition of redistributed band 3 by autologous IgG with subsequent attachment of C3b. Finally, the formation of C3b-IgG-band 3 immune complex accelerated the elimination of affected cells from circulation and led to the decline of erythrocyte life span during chronic arsenic toxicity.
- OSTI ID:
- 21344934
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 244, Issue 3; Other Information: DOI: 10.1016/j.taap.2010.01.009; PII: S0041-008X(10)00020-7; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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ALDEHYDES
ANTIOXIDANTS
ARSENIC
CHRONIC EXPOSURE
DEATH
ERYTHROCYTES
HYDROGEN PEROXIDE
HYDROXYL RADICALS
LIFE SPAN
MEMBRANE PROTEINS
OXIDATION
RATS
STRESSES
TOXICITY
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CHEMICAL REACTIONS
ELEMENTS
HYDROGEN COMPOUNDS
MAMMALS
MATERIALS
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PEROXIDES
PROTEINS
RADICALS
RODENTS
SEMIMETALS
VERTEBRATES