[논문]비타민 C 투여는 간 부분절제술에 의한 간 재생을 촉진 시킴

한선영; 황미열; 김아영; 이은미; 이은주; 이명미; 성수은; 김상협; 정규식

doi:10.5352/jls.2015.25.3.336

비타민 C 투여는 간 부분절제술에 의한 간 재생을 촉진 시킴
Vitamin C Promoted Liver Regeneration Following Partial Hepatectomy-induced Hepatic Injury in Senescence Marker Protein-30-deficient Mice 원문보기

생명과학회지 = Journal of life science, v.25 no.3 = no.179, 2015년, pp.336 - 344

초록
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비타민 C는 신진대사에 연관되어 있으며 특히 항산화 기능을 가지고 있다. 본 연구에서는 생체에서 비타민 C를 합성할 수 없는 SMP 30 녹아웃 마우스에 간 절제술을 시행하여 간 재생에서 비타민 C의 역할을 관찰하였다. 간 절제술은 마우스 중간엽 및 좌엽을 제거한 부분절제술을 수행하였다. 마우스는 간 절제술 후 비타민 C를 투여한 군(KV)와 비타민 C를 투여하지 않는 군(KO)로 나누어서 비타민 C의 효과를 관찰하였다. 결과 비타민 C를 투여한 KV 마우스의 간 회복이 투여하지 않는 KO 마우스에 비해 촉진되었다. KV 마우스의 혈액에서 관찰된 간소상 지표인 아스파르타산 아미노전달효소 및 간 손상 정도가 KO 마우스에 비해 낮게 관찰되었다. KV 마우스에서는 HGF와 c-Met에 의해서 TGF-베타 수용체 신호전달계가 활성화되고 세포주기 조절인자인 cyclin D1과 PCNA의 발현이 빠르게 증가되었다. 반면 KO 마우스에서는 활성화 되지 않았다. 또한 ERK와 GSK-3β 단백질의 활성화가 관찰되었으며 세포분열 간세포들의 유의적인 증가가 관찰되었다. 그리고 KV 마우스에서는 혈중 알부민의 농도가 높은 것으로 확인되었다. 따라서 본 실험결과는 SMP 30 결핍 마우스에서 비타민 C 투여는 간 재생시스템의 활성화와 이에 따른 빠른 회복을 초래한다.

Abstract ▼ AI-Helper

The capacity for liver regeneration involves a variety of nutritional factors. Vitamin C has multiple metabolic and antioxidant functions. In this study, we investigated the role of vitamin C in liver regeneration following hepatectomy in senescence marker protein (SMP)-30 knockout (KO) mice. Partial hepatectomy was performed by resecting the median and left lateral lobes of mice. Vitamin C accelerated liver recovery in SMP30 KO mice treated with vitamin C (KV). The livers of the KV mice exhibited lower levels of aspartate aminotransferase and lower injury than those of the KO mice. Increased type II transforming growth factor-β receptor (TGF-βRII)-mediated regeneration signaling was accompanied by HGF and cMet in the KV but not the KO mice. Consistent with this, the expression of cell cycle regulatory proteins, including cyclin D1 and proliferating cell nuclear antigen (PCNA), increased rapidly in the KV mice. Enhanced activation of ERK and GSK-3β proteins and a significantly increased number of binuclear hepatocytes were also detected in the livers of the KV mice. Moreover, the KV mice synthesized the highest levels of albumin. These data suggest that treating SMP30 knockout mice with vitamin C resulted in earlier recovery and liver regeneration by activation of the regeneration system.

주제어

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가설 설정

The ex- pression patterns were similar in the KV and WT groups. (B) The relative band densities were normalized to GAPDH. Each value is presented as the mean ± SEM.
In this study, we investigated the effect of vitamin C on hepatectomy-induced liver regeneration in SMP 30 KO mice.

제안 방법

These kinases phosphorylate a number of substrates and me- diate the induction of several genes including c-fos and cy- clin D1; this subsequently leads to cell cycle progression and growth in hepatocytes [35]. To investigate the effects of vita- min C on ERK activation, the phosphorylation of ERK was measured by immunoblotting. Vitamin C treatment led to the early activation of ERK in the KV and WT groups at 24 hr; in contrast, activation was only detected at 48 hr in the KO group (Fig.

데이터처리

(SEMs). The statistical significance between experimental groups was determined using Student's t-test or one-way analysis of var- iance (ANOVA). A p-value of <0.

이론/모형

Subsequently, the supernatants were centrifuged at 14, 000 rpm for 20 min at 4℃ to obtain soluble cytosolic proteins. The protein concentrations were then determined using the Bradford method. Protein samples were separated by 10-12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE).

성능/효과

ERK and Akt both transmit mitogenic signals via the Ras pathway, and they are activated by phosphorylation in the regenerat- ing liver in response to growth factors [6]. In this study, ERK was phosphorylated more rapidly and robustly in the KV group than in the KO group, suggesting that vitamin C could modulate hepatocyte replication by interacting with ERK signaling pathways. Interestingly, HGF and c-met lev- els were upregulated early after PHx in the KV group, but remained low in the KO group.

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