Role of intrinsic apoptosis in environmental exposure health outcomes.

Legacy and emerging toxicants of concern can modulate B cell lymphoma 2 (BCL-2) family protein expression and function, leading to excessive or insufficient levels of apoptosis and consequent pathogenesis. Apoptosis dysregulation undergirds a host of diseases of great public health concern, including cancer, autoimmune diseases, and neurodegenerative disorders. Recent discoveries show that apoptosis is dynamically regulated in healthy tissues across the lifespan, creating periods of heightened vulnerability to exposure-induced apoptosis such as early childhood. Understanding changes in BCL-2 family regulation and apoptotic sensitivity (priming) caused by environmental exposures can help us better understand potential health risks and mechanisms of disease. Novel agents that can modulate the apoptosis pathway may suppress or promote cell death in response to environmental toxicants, and ultimately prevent disease. Environmental exposures are linked to diseases of high public health concern, including cancer, neurodegenerative disorders, and autoimmunity. These diseases are caused by excessive or insufficient cell death, prompting investigation of mechanistic links between environmental toxicants and dysregulation of cell death pathways, including apoptosis. This review describes how legacy and emerging environmental exposures target the intrinsic apoptosis pathway to potentially drive pathogenesis. Recent discoveries reveal that dynamic regulation of apoptosis may heighten the vulnerability of healthy tissues to exposures in children, and that apoptotic signaling can guide immune responses, tissue repair, and tumorigenesis. Understanding how environmental toxicants dysregulate apoptosis will uncover opportunities to deploy apoptosis-modulating agents for the treatment or prevention of exposure-linked diseases. [ABSTRACT FROM AUTHOR]