Abnormal increase in the expression level of proliferating cell nuclear antigen (PCNA) in the liver and hepatic injury in rats with dietary cobalamin deficiency.
Dietary cobalamin (Cbl; vitamin B12) deficiency resulted in severe growth retardation in rats, and body weight in the Cbl-deficient rats at 20 wk of age was significantly lower compared with the age-matched Cbl-sufficient control rats. In contrast, liver weight, when normalized to body weight, was greater in the Cbl-deficient rats than in the controls (p<0.05). The expression level of proliferating cell nuclear antigen (PCNA), a marker for cell proliferation, in the liver was significantly enhanced in the deficient rats, suggesting that cell proliferation is abnormally activated in the liver under Cbl-deficient conditions. In addition, plasma alanine aminotransferase (ALT) activity, a marker for hepatic injury, was also significantly elevated in the deficient rats. When L-carnitine, which is used clinically for the treatment of Cbl-deficient patients with methylmalonic aciduria, was administered to the Cbl-deficient rats by intraperitoneal injection twice per day for 2 wk (each 0.5 mmol), the amount of methylmalonic acid excreted into the urine was significantly reduced, and the plasma ALT activity was lowered to a normal level. However, the PCNA expression in the liver was barely influenced by the treatment with carnitine. In contrast, when the deficient rats were fed an L-methionine-supplemented diet (4 g of L-methionine per kg of the diet) for 2 wk, the increased expression of PCNA was normalized.
Nakao
Motoyuki
M
Department of Applied Biological Chemistry, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan.
Kono
Nozomi
N
Adachi
Satoko
S
Ebara
Shuhei
S
Adachi
Tetsuya
T
Miura
Takumi
T
Yamaji
Ryoichi
R
Inui
Hiroshi
H
Nakano
Yoshihisa
Y
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D002331:Carnitine / Q000627:therapeutic use; D049109:Cell Proliferation; D006130:Growth Disorders / Q000209:etiology; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000097:blood / Q000209:etiology*; D008297:Male; D008715:Methionine / Q000627:therapeutic use; D008764:Methylmalonic Acid / Q000652:urine; D009929:Organ Size / Q000502:physiology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014806:Vitamin B 12 Deficiency / Q000150:complications* / Q000178:diet therapy; D014803:Vitamin B Complex / Q000627:therapeutic use
D015415:Biomarkers; D018809:Proliferating Cell Nuclear Antigen; D014803:Vitamin B Complex; D008764:Methylmalonic Acid; D008715:Methionine; D000410:Alanine Transaminase; D002331:Carnitine