Superoxide anion mediated mitochondrial dysfunction leads to hepatocyte apoptosis preferentially in the periportal region during copper toxicity in rats
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Superoxide anion mediated mitochondrial dysfunction leads to hepatocyte
apoptosis preferentially in the periportal region during copper toxicity in rats
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| Creator |
Roy, Dijendra Nath
Mandal, Samir Sen, Gargi Biswas, Tuli |
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| Subject |
Cell Biology & Physiology
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| Description |
Chronic exposure to copper induces hepatocellular apoptosis with greater injury in the periportal region
compared to the perivenous region. Here we have identified the factors responsible for the development
of regional damage in the liver under in vivo conditions. Enhanced production of reactive oxygen species
(ROS) with predominance of superoxide radical (O2•−) indicates the contribution of redox imbalance in
the process. This may be linked with copper catalyzed oxidation of GSH to GSSG resulting in the generation
of O2•−. Downregulation of Cu-Zn SOD in consequence of the degradation of this enzyme, causes
decreased dismutation of O2•−, that further contributes to the enhanced level of O2•− in the periportal
region. Decreased functioning of Mn SOD activity, reduction in mitochondrial thiol/disulphide ratio
and generation of O2•− were much higher in the mitochondria from periportal region, which point to
the involvement of this organelle in the regional hepatotoxicity observed during copper exposure. This
was supported by copper-mediated enhanced mitochondrial dysfunction as evident from ATP depletion,
collapse of mitochondrial membrane potential (MMP) and induction of mitochondrial permeability
transition (MPT). Results suggest the active participation of O2•− in inducing mitochondrial dysfunction
preferentially in the periportal region that eventually leads to the development of hepatotoxicity due to
copper exposure under in vivo condition.
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| Publisher |
Elsevier
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| Date |
2009
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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/1022/1/Chem_Bio(2009).pdf
Roy, Dijendra Nath and Mandal, Samir and Sen, Gargi and Biswas, Tuli (2009) Superoxide anion mediated mitochondrial dysfunction leads to hepatocyte apoptosis preferentially in the periportal region during copper toxicity in rats. Chemico-Biological Interactions, 182 (2-3). pp. 136-147. |
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| Relation |
http://dx.doi.org/10.1016/j.cbi.2009.08.014
http://www.eprints.iicb.res.in/1022/ |
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