TITLE:
Reactive oxygen species induced oxidative stress, neuronal apoptosis and alternative death pathways
AUTHORS:
Kandaswamy Selvakumar, Gunasekaran Krishnamoorthy, Prabhu Venkataraman, Jagadeesan Arunakaran
KEYWORDS:
Apoptosis; Caspases; Cell Death; Mitochondria; PCBs; Reactive Oxygen Species
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.4 No.1,
January
21,
2013
ABSTRACT: Reactive oxygen species (ROS) are produced as a byproduct
of cellular metabolic pathways and function as a critical second messenger in a
variety of intracellular signaling pathways. The excessive intracellular
generation of ROS on the other renders a cell oxidatively stressed. This
involvement of ROS in numerous diseases has been documented and at different
phases of the apoptotic pathway such as induction of mitochondrial permeability
transition and release of mitochondrial death amplification factors, activetion
of intracellular caspases and DNA damage has been clearly established. Cell
death by apoptosis is a part of normal development and maintenance of tissue
homeostasis. Polychlorinated biphenyls, one of the environmental pollutants
which are widely used in electrical industries and lipophilic and resistant to
biological decomposition accumulate through food chain. They are developmental
neurotoxicants which induce neuronal apoptosis. Our studies proved that
oxidative stress is induced promoting LPO and a decrease in all the
antioxidant enzymes in testis, epididymis, ventral prostate, seminal
vesicles, liver, kidney and brain regions. Neuronal damages were observed in
all the brain regions after PCB exposure. PCB increased caspase8 mRNA/protein
expression in hippocampus of adult rats. This upregulation results in
Fas-FasL mediated induction of hippocampal apoptosis. Performin/granzyme induced
apoptosis is the main pathway used by cytotoxic lymphocytes to eliminate
virus-infected or transformed cells. The production of ROS is greatly increased
during reperfusion phase when oxygen becomes available and the mitochondrial
respiratory chain is impaired. Furthermore, this is exacerbated by reduced
antioxidant defenses.