| Neonatal rodents, when compared to adults, are much more sensitive to naphthalene (NA), a pulmonary-specific bioactivated cytotoxicant. Studies in adult mice have shown that reactive NA metabolites significantly adduct several intracellular proteins, including Peroxiredoxin VI (Prx VI), an antioxidant protein known to protect against reactive oxygen species-mediated damage in the lungs of adult animals. Previous studies also show that pulmonary Prx VI is differentially expressed in the postnatal development of the rat, suggesting a role in developmental pulmonary response to toxicants. Our results in a mouse respiratory model corroborate previous studies in the rat---Prx VI mRNA and protein expression both increase expression with postnatal age in the lung in mixed airway epithelial cells. Prx VI protein was also more heavily concentrated in the nonciliated bronchiolar epithelial cell, the known target cell of NA, in weanling and adult animals. Exposure of NA to mice via intraperitoneal injection revealed that adult, but not neonatal mice, are able to increase Prx VI protein in the lung after NA challenge. To evaluate the specificity of Prx VI in the response to NA, we then exposed adult Prx VI -/- mice via inhalation to four hours of 10 ppm NA, the current NIOSH 8-hr time weighted average for human exposure. Prx VI -/- mice, when compared to control strains, were markedly more sensitive to NA, had an enhanced rate of development of toxicity, and increased extension of cellular damage more distally in the airways.;Based on our findings, we conclude that Prx6 is a postnatally developmentally expressed protein that is protective in the pulmonary response to NA. In addition, our results suggest that normal development of steady-state Prx VI protein levels during postnatal lung development help explain the enhanced sensitivity of neonates to NA-induced pulmonary cytotoxicity. |
