Submitted on July 29, 2005
Accepted on November 18, 2005
Amelioration of Oxidant Stress by the Defensin, Lysozyme
Hui-xian Liu1, Feng Zheng1, Qi Cao1, Bin Ren1, Li Zhu1, Gary E Striker1, and Helen Vlassara1*
1 Geriatrics, Mount Sinai School of Medicine, New York, NY, USA
* To whom correspondence should be addressed. E-mail: helen.vlassara{at}mssm.edu.
Reactive oxidant species (ROS), products of normal metabolism, cause oxidant injury if they accumulate in pathologic amounts. Lysozyme (LZ) contains an 18 amino acid domain which binds agents such as advanced glycation end-products (AGE) that generate ROS. We examined whether endogenous LZ affected physiologic, or baseline, anti-oxidant balance and provided protection against both acute and chronic oxidant injury, using paraquat and H2O2 as agents of acute injury and AGE for chronic injury. Hen egg-LZ-Tg mice had 3-fold higher serum LZ levels, decreased baseline AGE levels in serum and liver. These findings were linked to an enhanced baseline systemic GSH/GSSG ratio. Baseline levels of stress response genes p66Shc and c-Jun were also lower in liver tissue of LZ-Tg mice. Survival from severe oxidant injury induced by paraquat was 2-fold greater in LZ-Tg mice. In addition, LZ-Tg mice were resistant to chronic exogenous oxidant stress (OS) induced by AGE administration. Pre-incubation of hepatocytes (Hep-G2) with LZ suppressed redox balance at baseline, as well as OS after added paraquat, AGE, or H2O2. LZ also ameliorated paraquat-enhanced cell apoptosis in a dose-dependent manner, and suppressed AGE-induced p66Shc expression and c-Jun phosphorylation in Hep-G2 cells. Thus, LZ provides protection against acute and chronic oxidant injury by mechanisms involving suppression of ROS generation and of OS response genes.
