Regulation in the expression of vitamin B12-dependent enzyme, methymalonyl-CoA mutase
Regulation in the expression of vitamin B12-dependent enzyme, methymalonyl-CoA mutase
批准号:
17580116
负责人:
INUI Hiroshi
金额:
$2.27万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
2005
资助国家:
日本
项目状态:
已结题
起止时间:
2005 至 2007
中文摘要
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英文摘要
The aim of this work was to examine the effects of cobalamin (Cbl) on the activity and expression of L-methylmalonyl-CoA mutase (MCM) in rat liver and cultured COS-7 cells. The MCM holoenzyme activity was less than 5% of the total (holoenzyme+apoenzyme) activity in the liver although rats were fed a diet containing Cbl sufficiently. When weanling rats were maintained on a Cbl-deficient diet, the holo-MCM activity became almost undetectable at an age of 10 weeks. in contrast, a marked increase in the total-MCM activity occurred under the Cbl-deficient conditions, and at an age of 20 weeks it was about 3-fold higher in the deficient rats than in the controls (108 (SD 14.5) v.35 (SD 8.5) nmol/mg protein/min (n5); P<0.05). Western blot analysis confirmed that the MCM protein level increased significantly in the CBl-deficient rats. However, the MCM mRNA level, determination by realtime PCR, was rather decreased. When COS-7 cells were cultured in a medium in which 10% fetal bovine serum was … More the sole source of CBl, holo-MCM activity was barely detected. The supplementation of Cbl resulted in a great increase in the holo-MCM activity in the cells, but the activity did not exceed 30% of the total-MCM activity even in the presence of 10 μmol/l Cbl. In contrast, the total-MCM activity was significantly decrease by the Cbl supplementation, indicating that Cbl deficiency results in an increase in the MCM protein level in COS-7 cells as well as in rat liver.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-camitine, 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 weeks (each 0.5 mmol), the amount of methylmalonic add excreted into the urine was significantly reduced, and the plasma ALT activity was lowered to a normal level, suggesting that the decrease in the MCM holoenzyme activity results in hepatic injury in the Cbl-deficient rats. However; the PCNA expression in the liver was barely influenced by the treatment with camitine. 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 weeks, the increased expression of PCNA was normalized, suggesting that a decrease in methionine synthase due to Cbl deficiency induces the abnormal increase in the expression of PCNA. Less
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Title: Abnormal increase in the expression level of proliferating cell nuclear antigen (PCNA) in the liver and hepatic injury in rats with dietary cobalamin deficiency
标题:膳食钴胺素缺乏大鼠肝脏中增殖细胞核抗原(PCNA)表达水平异常升高和肝损伤
DOI:
--
发表时间:
2006
期刊:
J. Nutr. Sci. Vitaminol 52
影响因子:
--
作者:
[Nakao, M]
通讯作者:
M
Abnormal Increase in the Expression Level of Proliferating Cell Nuclear Antigen(PCNA) in the Liver and Hepatic Injury in Rats with Dietary Cobalamin Deficiency
膳食钴胺素缺乏大鼠肝脏中增殖细胞核抗原(PCNA)表达水平异常升高及肝损伤
DOI:
--
发表时间:
2006
期刊:
J. Nutri. Sci Vitaminol. 52
影响因子:
--
作者:
[Nakao, M., Kono, N., Adachi, S., Ebara, S., Adachi, T., Miura, T., Yamaji, R., Inui, H., Nakano, Y.]
通讯作者:
Y.
Molecular mechanisms of osteoarthritis regulation by Tace signaling
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批准号:26462285
-
项目类别:Grant-in-Aid for Scientific Research (C)
-
资助金额:$3.08万
-
财政年份:2014
-
负责人:INUI Hiroshi
-
依托单位:
Development and efficiency of a photoactivated doxifluridine donor encapsulated in liposome
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批准号:25670060
-
项目类别:Grant-in-Aid for Challenging Exploratory Research
-
资助金额:$2.16万
-
财政年份:2013
-
负责人:INUI Hiroshi
-
依托单位:
Comprehensive analysis of the inducer that degrades the extracellular matrix of articular cartilage
-
批准号:24659663
-
项目类别:Grant-in-Aid for Challenging Exploratory Research
-
资助金额:$2.41万
-
财政年份:2012
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负责人:INUI Hiroshi
-
依托单位:
Nonalcoholic steatohepatitis induced by the excess ingestion of fructose and its prevention by functional foods ingredient
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批准号:23580181
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$3.33万
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财政年份:2011
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负责人:INUI Hiroshi
-
依托单位:
Development of new caged-NO molecules having aromatic nitro compound as a basic framework and their NO-release abilities
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批准号:20750035
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项目类别:Grant-in-Aid for Young Scientists (B)
-
资助金额:$2.75万
-
财政年份:2008
-
负责人:INUI Hiroshi
-
依托单位:
Study on molecular mechanisms by which sweet constituents of Siraitia grosvenori exert anti-diabetes and anti-arteriosclerosis effects
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批准号:20580140
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$2.91万
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财政年份:2008
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负责人:INUI Hiroshi
-
依托单位:
Eucalyptus polyphenols inhibit intestinal fructose absorption, prevent adiposity, and improve diabetes mellitus
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批准号:14560107
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$2.18万
-
财政年份:2002
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负责人:INUI Hiroshi
-
依托单位:
Study in Signal Transduction of Platelet-derived Growth Factor which Participates in Chronic Hypertension
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批准号:06660159
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项目类别:Grant-in-Aid for General Scientific Research (C)
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资助金额:$1.15万
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财政年份:1994
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负责人:INUI Hiroshi
-
依托单位:
海外基金