Vitamin C depletion increases superoxide generation in brains of SMP30/GNL knockout mice.
Vitamin C (VC) has a strong antioxidant function evident as its ability to scavenge superoxide radicals in vitro. We verified that this property actually exists in vivo by using a real-time imaging system in which Lucigenin is the chemiluminescent probe for detecting superoxide in senescence marker protein-30 (SMP30)/gluconolactonase (GNL) knockout (KO) mice, which cannot synthesize VC in vivo. SMP30/GNL KO mice were given 1.5 g/L VC [VC(+)] for 2, 4, or 8 weeks or denied VC [VC(-)]. At 4 and 8 weeks, VC levels in brains from VC(-) KO mice were <6% of that in VC(+) KO mice. Accordingly, superoxide-dependent chemiluminescence levels determined by ischemia-reperfusion at the 4- and 8 weeks test intervals were 3.0-fold and 2.1-fold higher, respectively, in VC(-) KO mice than in VC(+) KO mice. However, total superoxide dismutase activity and protein levels were not altered. Thus, VC depletion specifically increased superoxide generation in a model of the living brain.
Kondo
Yoshitaka
Y
Aging Regulation, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
Sasaki
Toru
T
Sato
Yasunori
Y
Amano
Akiko
A
Aizawa
Shingo
S
Iwama
Mizuki
M
Handa
Setsuko
S
Shimada
Nobuko
N
Fukuda
Mitsugu
M
Akita
Masumi
M
Lee
Jaewon
J
Jeong
Kyu-Shik
KS
Maruyama
Naoki
N
Ishigami
Akihito
A
D000166:Acridines / Q000032:analysis / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001205:Ascorbic Acid / Q000235:genetics* / Q000378:metabolism; D001835:Body Weight; D001921:Brain / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics; D002265:Carboxylic Ester Hydrolases / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D049408:Luminescent Agents / Q000032:analysis / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D013481:Superoxides / Q000032:analysis / Q000378:metabolism*
D000166:Acridines; D000975:Antioxidants; D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D049408:Luminescent Agents; C513324:Rgn protein, mouse; D013481:Superoxides; C033472:10,10'-dimethyl-9,9'-biacridinium; D002265:Carboxylic Ester Hydrolases; C020579:gluconolactonase; D001205:Ascorbic Acid