Effects of soy protein isolate on LEC rats, a model of Wilson disease: mechanisms underlying enhancement of liver cell damage.
Soy-protein isolate (SPI) enhances liver cell damage in Long-Evans rats with a cinnamon-like coat color (LEC rats), which have a defect in Atp7b, the Wilson disease gene. Animals administered an SPI-diet from an age of six weeks died significantly earlier than those administered a control-diet, AIN-93G, from severe liver cell damage associated with jaundice. Since the liver copper level was higher with the SPI-diet than the control-diet, one of the reasons for SPI-toxicity to LEC rats might be due to the higher uptake of copper into liver cells. In the present study, liver levels of glutathione, and liver and intestinal mRNA and protein levels were determined for metallothionein, MT-1 and MT-2. Furthermore, liver and intestinal mRNA expression for the high affinity copper transporter, Ctr1, was determined. None of the parameters showed any significant differences between the SPI-diet and control-diet groups, except for Ctr1 mRNA levels in the liver. It is thus suggested that SPI enhances liver cell copper uptake through induction of Ctr1 expression and this might be the mechanism underlying increased liver damage in LEC rats.
Yonezawa
Kayo
K
Department of Nutritional Science, Tokyo University of Agriculture, 1-1 Sakuragaoka, 1, Setagaya, Tokyo, Japan.
Nakagama
Hitoshi
H
Tajima
Rie
R
Ushigome
Mitsunori
M
Ogra
Yasumitsu
Y
Suzuki
Kazuo T
KT
Yoshikawa
Kunie
K
Nagao
Minako
M
D000818:Animals; D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006527:Hepatolenticular Degeneration / Q000378:metabolism / Q000473:pathology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D030262:Soybean Proteins / Q000302:isolation & purification / Q000494:pharmacology*
D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; D008565:Membrane Proteins; D012333:RNA, Messenger; D030262:Soybean Proteins; D008668:Metallothionein; D005978:Glutathione; D019803:Glutathione Disulfide