Complete lack of vitamin C intake generates pulmonary emphysema in senescence marker protein-30 knockout mice.
Vitamin C (VC) is a potent antioxidant and plays an essential role in collagen synthesis. As we previously reported, senescence marker protein-30 (SMP30) knockout (KO) mice cannot synthesize VC due to the genetic disruption of gluconolactonase (i.e., SMP30). Here, we utilized SMP30 KO mice deprived of VC and found that VC depletion caused pulmonary emphysema due to oxidative stress and a decrease of collagen synthesis by the third month of age. We grew SMP30 KO mice and wild-type (WT) mice on VC-free chow and either VC water [VC(+)] or plain water [VC(-)] after weaning at 4 wk of age. Morphometric findings and reactive oxygen species (ROS) in the lungs were evaluated at 3 mo of age. No VC was detected in the lungs of SMP30 KO VC(-) mice, but their ROS increased 50.9% over that of the VC(+) group. Moreover, their collagen content in the lungs markedly decreased, and their collagen I mRNA decreased 82.2% compared with that of the WT VC(-) group. In the SMP30 KO VC(-) mice, emphysema developed [21.6% increase of mean linear intercepts (MLI) and 42.7% increase of destructive index compared with VC(+) groups], and the levels of sirtuin 1 (Sirt1) decreased 16.8%. However, VC intake increased the MLI 16.2% and thiobarbituric acid reactive substances 22.2% in WT mice, suggesting that an excess of VC can generate oxidative stress and may be harmful during this period of lung development. These results suggest that VC plays an important role in lung development through affecting oxidant-antioxidant balance and collagen synthesis.
Koike
Kengo
K
Department of Respiratory Medicine, Juntendo Univerity School of Medicine, Tokyo, Japan.
Kondo
Yoshitaka
Y
Sekiya
Mitsuaki
M
Sato
Yasunori
Y
Tobino
Kazunori
K
Iwakami
Shin-iciro
SI
Goto
Sataro
S
Takahashi
Kazuhisa
K
Maruyama
Naoki
N
Seyama
Kuniaki
K
Ishigami
Akihito
A
D000818:Animals; D001205:Ascorbic Acid / Q000502:physiology*; D001206:Ascorbic Acid Deficiency / Q000150:complications*; D002135:Calcium-Binding Proteins / Q000172:deficiency*; D024042:Collagen Type I / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency*; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000502:physiology; D011656:Pulmonary Emphysema / Q000209:etiology* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D056564:Sirtuin 1 / Q000096:biosynthesis
D002135:Calcium-Binding Proteins; D024042:Collagen Type I; D047908:Intracellular Signaling Peptides and Proteins; D017382:Reactive Oxygen Species; C513324:Rgn protein, mouse; D056564:Sirtuin 1; D001205:Ascorbic Acid