• Journal of Life Science
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• v.29 no.11
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• pp.1179-1191
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• 2019

Cancer cells undergo the epithelial-mesenchymal transition (EMT) and show unique oncogenic metabolic phenotypes such as the glycolytic switch (Warburg effect) which are important for tumor development and progression. The EMT is a critical process for tumor invasion and metastasis. High-mobility group box 1 (HMGB1) is a chromatin-associated nuclear protein, but it acts as a damage-associated molecular pattern molecule when released from dying cells and immune cells. HMGB1 induces the EMT, as well as invasion and metastasis, thereby contributing to tumor progression. Here, we show that HMGB1 induced the EMT by activating Snail. In addition, the HMGB1/Snail cascade was found induce a glycolytic switch. HMGB1 also suppressed mitochondrial respiration and cytochrome c oxidase (COX) activity by a Snail-dependent reduction in the expression of the COX subunits COXVIIa and COXVIIc. HMGB1 also upregulated the expression of several key glycolytic enzymes, including hexokinase 2 (HK2), phosphofructokinase-2/fructose-2,6-bisphosphatase 2 (PFKFB2), and phosphoglycerate mutase 1 (PGAM1), in a Snail-dependent manner. However, HMGB1 was found to regulate some other glycolytic enzymes including lactate dehydrogenases A and B (LDHA and LDHB), glucose transporter 1 (GLUT1), and monocarboxylate transporters 1 and 4 (MCT1 and 4) in a Snail-independent manner. Transfection with short hairpin RNAs against HK2, PFKFB2, and PGAM1 prevented the HMGB1-induced EMT, indicating that glycolysis is associated with HMGB1-induced EMT. These findings demonstrate that HMGB1 signaling induces the EMT, glycolytic switch, and mitochondrial repression via Snail activation.

• Journal of The Korean Society of Grassland and Forage Science
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• v.27 no.2
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• pp.93-100
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• 2007

This study was conducted to determine the effects of different levels (10, 12 and 15%) of crude protein (CP) in total mixed ration (TMR) on dry matter intake, digestibility and nitrogen balance of Korean black goats in the stage of early pregnancy and to obtain information on their optimal dietary levels of CP. In the present study, 12 Does of Korean black goats in the early pregnancy were allotted to four unreplicated groups by dietary level of CP and then they were housed in individual metabolism cages with completely randomized design throughout 30 days with 20 days adaptation and 10 days collection periods. Does in Control were fed a conventional diet and does in TMR10, TMR12 and TMR15 were fed a diet adjusted to about 10, 12 and 15% CP, respectively. Dry matter(DM) contents ranged from 89 to 91% in treatments. There were no differences fur fiber contents among three CP levels of TMR, showing that ADF and NDF had 18.57 to 19.85, and 53.41 to 54.80, respectively. Crude protein contents for three TMR treaements had 10.61, 12.15 and 14.97%, respectively. However, non-fibrous carbohydrate (NFC) contents decreased with increasing CP levels in treatments. Meanwhile, Intakes of DM, nutrients and digestible nutrients were significantly (p<0.05) higher in TMR15 and control than in TMR10 and TMR12. Moreover, DM intake per metabolic body weight and theit ratio per body weight was significantly (p<0.05) higher for control and TMR15 than other treatments. DM digestibility was not significantly different among treatments, but ether extract digestibility of treatments was significantly (p<0.05) higher than that of control, but there was no significant difference among treatments. Nitrogen retention significantly (p<0.05) increased with increasing CP levels in TMR, and TMR15 was highest among treatments. Our results showed that the increasing CP levels in TMR increased DM intake and nitrogen retention and suggested that the optimal dietary CP levels under TMR feeding system in early pregnant Korean black goats could be estimated for at least 15%.