Correlation between Hyper-Sensitivity to Hydrogen Peroxide and Low Defense against Ca²⁺ Influx in Cataractogenic Lens of Ihara Cataract Rats

Abstract

Our previous studies have demonstrated that lipid peroxidation in the lenses of hereditary cataract model rats (Ihara cataract rat (ICR)/f rats) caused a dysfunction in Ca²⁺ regulation. In the present study, we investigated the effect of in vitro hydrogen peroxide (H₂O₂) stimulation on lipid peroxide (LPO) and the activities of sarco-/endoplasmic reticulum and plasma membrane Ca²⁺-ATPase (SERCA and PMCA) in the ICR/f rat lenses. An increase in LPO level and decreases in the SERCA and PMCA activities were observed with increasing H₂O₂ concentration, and pretreatment with diethyldithiocarbamate, a potent radical scavenger, attenuated these changes in normal and ICR/f rat lenses. The glutathione levels, glutathione peroxidase and glutathione reductase activities are significantly lower in ICR/f rat lenses than in normal rat lenses. Furthermore, we presented as two kinetic parameters such as DP (defense point) and K_s (reactive constant) analyzed from above various biological responses vs. H₂O₂ concentration–profile curves using a one-exponential equation. The DPs for LPO, SERCA and PMCA in ICR/f rat lenses is lower than in normal rat lenses. In contrast to the results in DP, the K_s for LPO, SERCA and PMCA in ICR/f rat lenses is higher than in normal rat lenses. In addition, the closed relationship of was observed between DP and K_s for LPO, SERCA and PMCA. These results show that the resistance to H₂O₂ in the ICR/f rat lenses is lower than that of normal rats. The DP and K_s values can provide an useful information for resistances to various stimuli in cells and tissues.