Abstract
Senescence Marker Protein-30 (SMP30) was originally identified as a novel protein in the rat liver, the expression of which decreases with aging. Recently, we identified SMP30 as the lactone-hydrolyzing enzyme gluconolactonases (GNL) of animal species. GNL was a key enzyme which involve in vitamin C biosynthesis, and the essential role of SMP30 in this synthetic process was verified by a nutritional study. SMP30 knockout mice developed symptoms of scurvy when fed a vitamin C-deficient diet, verifying the pivotal role of SMP30 in vitamin C biosynthesis. Moreover, SMP30 knockout mice were shorter in life span than the wild type when fed autoclaved mouse chow contained 〜55mg/kg of vitamin C, which we now know contains too little vitamin C to maintain normal levels of vitamin C in tissues. These results demonstrate that vitamin C deficiency accelerates aging. Aging and smoking are considered as major contributing factors for the development of pulmonary emphysema. We evaluated whether SMP30/GNL knockout mice are susceptible to oxidative stress associated with aging and smoking. In the lungs of SMP30/GNL knockout mice, airspace enlargement of pulmonary alveolus occurred when fed a vitamin C-deficient diet. Moreover, cigarette smoke exposure generated marked airspace enlargement with significant parenchymal destruction in the SMP30/GNL knockout mice but not in the wild type mice. Our results suggest that vitamin C protects mice lungs from oxidative stress associated with aging and smoking. The SMP30/GNL knockout mice could be useful animal models for investigating age-related lung diseases including cigarette smoke-induced chronic obstructive pulmonary disease (COPD).
