Reduced Cellular Redox Status induces 4-Hydroxynonenal-Mediated Caspase 3 Activation Leading to Erythrocyte death during Chronic Arsenic Exposure in Rats
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Reduced Cellular Redox Status induces 4-Hydroxynonenal-Mediated Caspase 3
Activation Leading to Erythrocyte death during Chronic Arsenic Exposure in Rats
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| Creator |
Biswas, Debabrata
Sen, Gargi Biswas, Tuli |
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| Subject |
Cell Biology & Physiology
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| Description |
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 (H2O2) from the early
stages of arsenic exposure, while superoxide (O2•−) and hydroxyl radical (•OH) 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 HNEmediated
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.
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| Publisher |
Elsevier
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| Date |
2010
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/1026/1/PDF%2DTAAP(2010).pdf
Biswas, Debabrata and Sen, Gargi and Biswas, Tuli (2010) Reduced Cellular Redox Status induces 4-Hydroxynonenal-Mediated Caspase 3 Activation Leading to Erythrocyte death during Chronic Arsenic Exposure in Rats. Toxicology and Applied Pharmacology, 244. pp. 315-327. |
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| Relation |
http://dx.doi.org/10.1016/j.taap.2010.01.009
http://www.eprints.iicb.res.in/1026/ |
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