Reactive oxygen species induced oxidative stress, neuronal apoptosis and alternative death pathways

Abstract

Reactive oxygen species (ROS) are produced as a by-product of cellular metabolic pathways and function as a critical second messenger in a variety of intra-cellular signaling pathways. The excessive intracellu-lar generation of ROS on the other renders a cell oxidatively stressed. This involvement of ROS in nu-merous diseases has been documented and at differ-ent phases of the apoptotic pathway such as induction of mitochondrial permeability transition and release of mitochondrial death amplification factors, active-tion of intracellular caspases and DNA damage has been clearly established. Cell death by apoptosis is a part of normal development and maintenance of tis-sue 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 de-crease in all the antioxidant enzymes in testis, epidi-dymis, ventral prostate, seminal vesicles, liver, kidney and brain regions. Neuronal damages were observed in all the brain regions after PCB exposure. PCB in-creased caspase8 mRNA/protein expression in hip-pocampus of adult rats. This upregulation results in Fas-FasL mediated induction of hippocampal apop-tosis. Performin/granzyme induced apoptosis is the main pathway used by cytotoxic lymphocytes to eli-minate virus-infected or transformed cells. The pro-duction of ROS is greatly increased during reperfu-sion phase when oxygen becomes available and the mitochondrial respiratory chain is impaired. Fur-thermore, this is exacerbated by reduced antioxidant defenses.