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 Ca(2+) regulation. In the present study, we investigated the effect of in vitro hydrogen peroxide (H(2)O(2)) stimulation on lipid peroxide (LPO) and the activities of sarco-/endoplasmic reticulum and plasma membrane Ca(2+)-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 H(2)O(2) 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. H(2)O(2) 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 H(2)O(2) 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.