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Hepatocyte-specific Prominin-1 protects against liver injury-induced fibrosis by stabilizing SMAD7
Lee Hyun,Yu Dong-Min,Bahn Myeong-Suk,Kwon Young-Jae,Um Min Jee,Yoon Seo Yeon,Kim Ki-Tae,Lee Myoung-Woo,Jo Sung-Je,Lee Sungsoo,Koo Seung-Hoi,Jung Ki Hoon,Lee Jae-Seon,Ko Young-Gyu 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
Prominin-1 (PROM1), also known as CD133, is expressed in hepatic progenitor cells (HPCs) and cholangiocytes of the fibrotic liver. In this study, we show that PROM1 is upregulated in the plasma membrane of fibrotic hepatocytes. Hepatocellular expression of PROM1 was also demonstrated in mice (Prom1CreER; R26TdTom) in which cells expressed TdTom under control of the Prom1 promoter. To understand the role of hepatocellular PROM1 in liver fibrosis, global and liver-specific Prom1-deficient mice were analyzed after bile duct ligation (BDL). BDL-induced liver fibrosis was aggravated with increased phosphorylation of SMAD2/3 and decreased levels of SMAD7 by global or liver-specific Prom1 deficiency but not by cholangiocyte-specific Prom1 deficiency. Indeed, PROM1 prevented SMURF2-induced SMAD7 ubiquitination and degradation by interfering with the molecular association of SMAD7 with SMURF2. We also demonstrated that hepatocyte-specific overexpression of SMAD7 ameliorated BDL-induced liver fibrosis in liver-specific Prom1-deficient mice. Thus, we conclude that PROM1 is necessary for the negative regulation of TGFβ signaling during liver fibrosis.
(Hoi Seon Lee) 한국응용생명화학회 1999 Applied Biological Chemistry (Appl Biol Chem) Vol.42 No.1
Sucrose synthase (EC 2.4.1.13) has been purified from the plant cytosolic fraction of chickpea (Cicer arietinum L. cv. Amethyst) nodules. The native enzyme had a molecular mass of 356±15 kD. The subunit molecular mass was 87±2 kD, and a tetrameric structure is proposed for sucrose synthase of chickpea nodule. Optimum activities in the sucrose cleavage and synthesis directions were at pH 6.5 and 9.0, respectively. The purified enzyme displayed typical hyperbolic kinetics with substrates in cleavage and synthesis reactions. Chickpea nodules sucrose synthase had a high affinity for UDP (K_m, 8.0 μM) and relatively low affinities for ADP (K_m, 0.23 mM), CDP (K_m, 0.87 mM), and GDP (K_m, 1.51 mM). The K_m for sucrose was 29.4 mM. In the synthesis reaction, UDP-glucose (K_m, 24.1 μM) was a more effective glucosyl donor than ADP-glucose (K_m, 2.7 mM), and the K_m for fructose was 5.4 mM. Divalent cations, such as Ca^(2+), Mg^(2+), and Mn^(2+), stimulated the enzyme activity in both the cleavage and synthesis directions, and the enzyme was very sensitive to inhibition by HgCl₂ and CuSO₄.
Suppression Effect of Purpurin Derivatives on Nitric Oxide Synthase
Lee, Hoi-Seon The Korean Society for Applied Biological Chemistr 2011 Applied Biological Chemistry (Appl Biol Chem) Vol.54 No.2
The inhibitory effects of Rubia tinctorum root-derived materials against nitric oxide (NO) production were assessed by evaluation of NO production and inducible NO synthase (iNOS) expression, and compared to those of trihydroxyanthraquinone derivatives. The inhibitory effect of 1,2,4-trihydroxyanthraquinone (purpurin) from R. tinctorum roots against NO production was 60.7 and 38.5% at 2.5 and $1.25{\mu}g/mL$, respectively. Inhibitory effect of 1,2,7-trihydroxyanthraquinone was 52.5% at $2.5{\mu}g/mL$. Suppression effects of 1,2,4-trihydroxyanthraquinone on iNOS expression were confirmed by western blot analysis.